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After over a decade, I believe I have cured my POIS. I wanted to open source my supplement stack to get feedback/improvemnets and to help others going through what I went through.
During orgasm there is a transient increase in norepinephrine release [1] (see Neuroendocrine responses to arousal and orgasm (https://poiscenter.com/forums/index.php?topic=2900.msg26917#msg26917)).
(https://i.imgur.com/43RWkMg.png)
Postorgasmic illness syndrome (POIS) occurs when there is an overexpression of the α1-adrenergic (a1A) receptor and a subsequent over-stimulation of a1A by rising norepinephrine levels [2]. Part of the effect of α1-adrenergic , a1A, stimulation is to obtain methyl groups (choline) from the phospholipid bilayer (http://aocs.files.cms-plus.com/LipidsLibrary/images/ImportedImages/lipidlibrary/animbio/phospholipases/Figure04.png) stored in the form of phosphatidylcholine (PC) [3]. a1A stimulation upregulates the enzymes Phospholipase A2 and C, which remove a PC-arachidonic acid molecule from the cell wall (lipid bilayer) and separates PC from arachidonic acid (omega-6 fatty acid, AA) [4]. PC is now free to produce choline and replenish the pool of methyl groups consumed in both semen and neurotransmitter production.
However, the release of arachidonic acid, or AA (https://en.wikipedia.org/wiki/Arachidonic_acid#The_synthesis_and_cascade_in_humans), is problematic since it is a key substrate for the production of inflammatory hormones by the enzymes 5-LOX, COX-2 and the CYP450 group [4]. It is the rapid release of AA and mass production of inflammatory hormones (such as prostaglandin E2) that triggers sickness associated with POIS.
During normal sexual activity, histamine is not elevated (Becker et. al. 2011 (https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0272.2011.01222.x)). However, POIS-like symptoms could be stimulated by non-coital external allergens (food, pollution, etc...), by replacing norepinephrine with either histamine or glutamate, and replacing a1A receptor with either the h1-histaminergic (h1H) or NMDA (NR2B) receptor. For example, histamine stimulation of h1H upregulates the enzyme Phospholipase A2, leading to the same release of PC and AA as discussed above [5, 6].
(https://i.imgur.com/cpuXuGZ.png)
Blocking both of the processes represented by red arrows in the figure above would, according to this theory, stop POIS. In other words, each red path is a required step for the disease to manifest. And the upregulation of NF-kB (NF-kappa Beta) by reactive oxygen species (ROS) is a required step for the increased production of COX-2 and inflammation (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769).
We can refer to the cascade of events, starting with simulation of the a1A, h1H, NR2B receptors and ending with the production of inflammatory prostaglandins, as the POIS Cascade. To stop POIS, you have to modify the POIS Cascade by inhibiting three key events:
1. α1-adrenergic and h1-histamine receptor overexpression
2. NF-kB upregulation and inflammatory cytokine (https://en.wikipedia.org/wiki/Cytokine) production
3. arachidonic acid production and release from the PC-arachidonic acid complex
(1) a1A receptor expression is down regulated by the universal methyl group donor S-adenosyl-methionine (SAM-e) by donating its methyl group through methyltransferase enzymes [7]. In this way, SAM-e prevents the breakdown of the phospholipid bilayer [8] and the subsequent metabolism of AA [9]. h1H receptor expression is down regulated by Protein Kinase C (PKC) inhibition [10]. PKC is potently inhibited by thiamine diphosphate, the active form of vitamin B1 [11]. Moreover, thiamine supplementation reduces median histamine levels [12].
(2) Vitamin D3 is a strong inhibitor of NF-kB and COX-2 production [Ref link (http://www.jbc.org/content/289/17/11681.long)]. D3 accomplishes this by inhibiting the production of inflammatory cytokines such as TNF-a, IL-1B, IL-6, etc... [schematic diagram (https://i.imgur.com/xXCit9H.jpg)]
(3) In the absence of dietary AA, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce AA incorporation into the phospholipid bilayer and decrease the production of inflammatory prostaglandins such as PGE2 [4, 13]. Moreover, EPA directly competes with AA for access to enzymes 5-LOX and COX-2 [4]. And unlike AA, the metabolic products of EPA interaction with these enzymes are anti-inflammatory (link (https://en.wikipedia.org/wiki/Resolvin)).
For a literature review of POIS related research see POIS literature review (https://poiscenter.com/forums/index.php?topic=2683.msg23777#msg23777):
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Below I provide two separate supplement stacks that have given me complete relief of POIS symptoms. "The Betaherpesvirinae stack" is a prepack that targets a specific reactivation mechanism of cytomegalovirus (CMV, HHV-5) and herpes virus 6 (HHV-6) involving suppression of NF-kB and COX activity (see RefSE1 (https://www.ncbi.nlm.nih.gov/pubmed/8943952), RefSE2 (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). More details on how herpes viruses may initiate POIS can be found here (link (http://poiscenter.com/forums/index.php?topic=2683.msg23764#msg23764)). "The POIS Cascade stack" is the general daily health supplement (and vegan diet) regime that I use to treat my POIS, NE, and reduce exercise induced DOMS. These are two separate stacks which are not meant to be taken together. The below quantities for each stack are listed per dose.
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (https://www.amazon.com/Jarrow-Formulas-Promotes-Strength-Enteric-Coated/dp/B0013OVW0O/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1504971308&sr=1-4&keywords=sam-e%2B200mg&th=1) (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---Pyridoxal-5-phosphate, P-5-P vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Metafolin or folinic acid, vitamin B9 (less than 200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (>50mcg, sublingual) [methyl group cycler] (https://www.amazon.com/Jarrow-Formulas-Pyridoxal-5-phosphate-Lozenges-Supports/dp/B01IJR5VM2/ref=sr_1_26?keywords=Metafolin&qid=1559879958&s=gateway&sr=8-26)
---Pick from one of the following three methyl group donors:
1. tri-methylglycine (https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_7_s_it?s=hpc&ie=UTF8&qid=1504972619&sr=1-7&keywords=betaine&th=1), betaine (1.5g) [methyl group donor]
2. alpha-glycerophosphocholine (https://www.amazon.com/NOW-Alpha-GPC-300-Capsules/dp/B001RYKA3U/ref=sr_1_5_a_it?ie=UTF8&qid=1504972471&sr=8-5&keywords=alpha-GPC&th=1), alpha-GPC (600mg) [methyl group donor]
3. liposomal vitamin C (2g) (also containing phosphatidylcholine) (source1 (https://www.amazon.com/Lipo-Naturals-Preservatives-Encapsulated-Bioavailability/dp/B00IMO09IO/ref=sr_1_5?crid=HS73GAAZ6Q1I&keywords=liposomal%2Bvitamin%2Bc&qid=1566262619&s=gateway&sprefix=liposomal%2B%2Caps%2C182&sr=8-5&th=1), source2 (https://www.amazon.com/DACHA-Nutrition-Natural-Liposomal-Vitamin/dp/B07DR13XSX/ref=sr_1_10?crid=HS73GAAZ6Q1I&keywords=liposomal+vitamin+c&qid=1566262619&s=gateway&sprefix=liposomal+%2Caps%2C182&sr=8-10), source3 (https://www.amazon.com/Lypo-Spheric-Vitamin-Bioavailability-Professionally-Phospholipids/dp/B000CD9XGC/ref=sr_1_3?crid=HS73GAAZ6Q1I&keywords=liposomal+vitamin+c&qid=1566262490&s=gateway&sprefix=liposomal+%2Caps%2C182&sr=8-3))
With food, twice daily (fat soluble):
---Benfotiamine (https://www.amazon.com/Life-Extension-Benfotiamine-Thiamine-vegetarian/dp/B000MYXVTQ/ref=sr_1_18_s_it?s=hpc&ie=UTF8&qid=1504972698&sr=1-18&keywords=Benfotiamine), vitamin B1 (150mg) [h1H downregulator]
---conjugated linoleic acid, CLA (2g) [NF-kB inhibitor and COX-2 downregulator] (https://www.amazon.com/Evlution-Nutrition-Conjugated-Supplement-Stimulant-Free/dp/B01HXGY7RU/ref=sr_1_7_s_it?s=hpc&ie=UTF8&qid=1525925575&sr=1-7&keywords=cla&dpID=51-yago%252Bn7L&preST=_SY300_QL70_&dpSrc=srch)
---eicosapentaenoic acid, EPA (900mg) [AA synthesis inhibitor, AA blocker]
---docosahexaenoic acid, DHA (150mg) [AA synthesis inhibitor] (https://www.amazon.com/MuscleTech-Omega-Black-Onyx-softgels/dp/B01IBQH462/ref=sr_1_fkmr0_1_s_it?s=hpc&ie=UTF8&qid=1504972154&sr=1-1-fkmr0&keywords=Omega+4X+SX7+Black+Onyx)
---vitamin D3 (1000 IU) [NF-kB inhibitor and COX-2/IDO/TDO down-regulator] (https://www.amazon.com/NOW-Vitamin-Liposomal-Spray-2-Ounce/dp/B0045MJNCU/ref=sr_1_7_s_it?s=hpc&ie=UTF8&qid=1525926073&sr=1-7&keywords=vitamin+d+spray)
Betaherpesvirinae stack:
Taken 2 hours prior to sexual activity (prepack):
Vasoconstrictors (my modified version of Excedrin (https://www.excedrin.com/products/)):
---Paracetamol 500mg
---indomethacin 50mg
---caffeine 130mg (from Matcha green tea, one brewed cup, whole powder)
Immune regulators:
---vitamin D3 (2000IU sublingual) (https://www.amazon.com/NOW-Vitamin-Liposomal-Spray-2-Ounce/dp/B0045MJNCU/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1531365035&sr=1-4&keywords=vitamin+d3+k2+spray&dpID=41iFg2gwtWL&preST=_SY300_QL70_&dpSrc=srch)
---citrulline malate (6g)
---liposomal vitamin C (2g) (also containing phosphatidylcholine) (source1 (https://www.amazon.com/Lipo-Naturals-Preservatives-Encapsulated-Bioavailability/dp/B00IMO09IO/ref=sr_1_5?crid=HS73GAAZ6Q1I&keywords=liposomal%2Bvitamin%2Bc&qid=1566262619&s=gateway&sprefix=liposomal%2B%2Caps%2C182&sr=8-5&th=1), source2 (https://www.amazon.com/DACHA-Nutrition-Natural-Liposomal-Vitamin/dp/B07DR13XSX/ref=sr_1_10?crid=HS73GAAZ6Q1I&keywords=liposomal+vitamin+c&qid=1566262619&s=gateway&sprefix=liposomal+%2Caps%2C182&sr=8-10), source3 (https://www.amazon.com/Lypo-Spheric-Vitamin-Bioavailability-Professionally-Phospholipids/dp/B000CD9XGC/ref=sr_1_3?crid=HS73GAAZ6Q1I&keywords=liposomal+vitamin+c&qid=1566262490&s=gateway&sprefix=liposomal+%2Caps%2C182&sr=8-3))
Drug detox antioxidants:
---N-acetylcysteine (1.2g (https://www.amazon.com/Life-Extension-N-Acetyl-L-Cysteine-Vegetarian-Capsules/dp/B008ML8D4O/ref=sxbs_sxwds-stvp?keywords=N-acetylcysteine%2Bselenium&pd_rd_i=B008ML8D4O&pd_rd_r=11d4a26b-eff0-456b-919c-8f712a1527d5&pd_rd_w=3ngLH&pd_rd_wg=TbWlT&pf_rd_p=a6d018ad-f20b-46c9-8920-433972c7d9b7&pf_rd_r=7CPBTWFGP7AZSB1NHGX8&qid=1559880742&s=gateway&th=1))
---selenomethionine (200 micrograms)
Note: Many of these supplements have slow diffusion across the blood/brain barrier and/or slow incorporation into the phospholipid bilayer. So it may take 3 to 4 weeks of consistent supplementation before you are able to assess the full benefit. I continue daily maintenance of supplementation with the POIS Cascade Stack even after seeing my symptoms disapear.
About SAM-e: SAM-e plays a unique role in the Homocysteine Cycle (https://i.imgur.com/hq96vF1.jpg) (see #1) and cannot be replaced by any other methyl donor or cycler. SAM-e may upset your stomach the first time you take it; this is normal. Do not take SAM-e within 5 hours of your typical bedtime or you may experience trouble going to sleep.
About Methyl donors: For the alpha-GPC option, start out taking apha-GPC once daily at 300mg and work your way up to a twice daily dose at 600mg over the course of one week. Large doses of alpha-GPC without being acclimated first could cause choline-induced lower-back and upper-leg pain. The advantage of taking methyl donors such as choline and betaine (TMG) is that they offer a folate-independent path (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/) to reducing homocysteine and recycling SAM-e (see #2 in Homocysteine Cycle (https://i.imgur.com/hq96vF1.jpg)). I believe this folate-independent and (MTHFR)-independent SAM-e production by choline/betaine was critical for eliminating my POIS symptoms. Di-methyglycine (DMG) does not offer this advantage, and could make problems worse (https://books.google.com/books?id=3K3ECQAAQBAJ&q=%22dmg+is+a+potent+inhibitor+of+BHMT%22#v=snippet&q=%22dmg%20is%20a%20potent%20inhibitor%20of%20BHMT%22&f=false) for those who are undermethylated/folate-deficient.
About vitamin B6: The amount of vitamin B6 here (2mg) is roughly 100% of the US recommended daily allowance (RDA) (https://ods.od.nih.gov/pdf/factsheets/VitaminB6-Consumer.pdf). My daily B6 consumption does not exceed 25mg as an upper limit. However, typical branded B6 and B complex supplements may exceed 200mg (10,000%) and are toxic when taken daily.
About folate B9: (200 microgram) is a safe daily dose. For folate-cancer data, please see Table 1: cancer endpoints (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790187/table/T1/) under the Outcomes heading.
About vitamin B12: B12 has an extremely low toxicity (http://lpi.oregonstate.edu/mic/vitamins/vitamin-B12#toxicity). Between 50 to 1000 mcg can be taken per day.
About Omega-3: Because of the way that EPA is metabolized in the body, it does not have any toxicity in the body. So, the more the merrier! DHA has a theoretical toxicity, but this has never been demonstrated in vivo. Omega-3s compete with and are a substitute for omega-6s like AA (https://www.psychologytoday.com/blog/in-the-zone/201204/what-are-the-real-differences-between-epa-and-dha). Therefore, it may be just as important to reduce dietary omega-6 (AA) consumption (https://www.ncbi.nlm.nih.gov/pubmed/9590632). I have almost eliminated certain fatty-meats (i.e. pork and beef) from my diet since this is the largest source of arachidonic acid in North America.
About Vasoconstrictors: The vasocontrictors (Paracetamol 500mg, indomethacin 50mg, caffeine 130mg) can be replaced by Excedrin (https://www.amazon.com/dp/B00AAXFD90?aaxitk=zfnMDdpwtGG-2PXNrZoeSA&pd_rd_i=B00AAXFD90&pf_rd_m=ATVPDKIKX0DER&pf_rd_p=3930100107420870094&pf_rd_s=desktop-sx-top-slot&pf_rd_t=301&pf_rd_i=Excedrin&hsa_cr_id=1708041030901&th=1) (acetaminophen 500mg, aspirin 500mg, caffeine 130mg). Paracetamol, which is another name for acetaminophen or Tylenol, is a Endocannabinoid Enhancer (https://en.wikipedia.org/wiki/Endocannabinoid_enhancer). The three drugs work in synergy to downregulate COX-1 and COX-2 activity. The respective roles of each should be considered when substituting or removing the ingredients. The research indicates that selenomethionine detoxifies indomethacin (Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/21532324), Ref2 (https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12808), Ref3 (https://www.ncbi.nlm.nih.gov/pubmed/23456451), Ref4 (https://journals.physiology.org/doi/full/10.1152/ajpgi.00125.2012)) and N-acetylcyteine detoxifies acetaminophen/Tylenol (Ref4 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614100/), Ref5 (https://poisoncontrol.utah.edu/newsletters/pdfs/toxicology-today-archive/Vol7_No1.pdf), Ref6 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf)). In adddition to inhibiting NF-kB, selenomethione and N-acetylcyteine boost glutathoine and should be taken to minimized potential side-effects of Excedrin/Betaherpesvirinae stacks. The below figure shows the dose timing for the vasoconstrictors. tstart is when the dosing starts. tmax is when sexual activity can begin. t1/2 is the window of time when the vasocostrictor is effective (half-life). This effective window for the Betaherpesvirinae stack is about 3 hours.
(https://i.imgur.com/vyxg6r7.png)
Final note:
I avoid concentrated extracts of curcumin, luteolin, quercetin, ginger, and peppermint because from my experience, these flavonoids (https://en.wikipedia.org/wiki/Phytoestrogens#Structure) reduced the quality and quantity of my semen. I noticed this effect in my semen when I used to take concentrated extracts of curcumin and luteolin. I discovered this by accident about a year and a half ago after taking large doses of curcumin and luteolin. I noticed a slight thinning of my semen and reduced volume. When I stopped taking curcumin and luteolin (daily), after about a week my semen recovered. Thinking that this was a coincidence, I resumed only curcumin (daily), but after a few days I noticed the same effects on reduced volume.
These were not rigorous test, but after some research, I found that flavonoids mimic steroids in the body for their effects. In other words, flavonoids derive their beneficial effects primarily through steroid signaling [15 (http://www.cancersupportivecare.com/estrogenherb.html)] (anti-inflammatory[16], anti-oxidant [17], mast cell stabilizing [18], IDO/TDO inhibiting [19], neuroprotection [20], cAMP-PDE inhibitor [21]). The US Environmental Protection Agency list quercetin as one of the strongest estrogens (https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-estrogen-receptor-bioactivity) found in the environment [22]. However, it is important to point out that whole-herbs like licorice (contains quercetin) (https://benthamopen.com/ABSTRACT/TORSJ-6-1) and tumeric do not appear to have this negative effect (http://www.sciencedirect.com/science/article/pii/S2214750015300652), and I have not experienced any negative side effects on sperm when taking whole-herbs. My concern about using flavonoid extracts is purely out of concern for the health of my reproductive system, and is not related to reducing POIS symptoms. Like steroids, it appears that flavonoids (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851288/) can also potently reduce inflammation and other POIS symptoms. I do make it a point to get natural levels of flavonoids through diet (capers, onions, apples, broccoli, spicy foods, tumeric-based vegetable currys). However, I personally do not take active hormones.
For sperm consistent herbal supplements, I sometimes like taking lycopene, lutein, zeaxanthin, and oils like olive oil, ahiflower oil and/or cinnamon oil. Each of these oils has a unique protocol for supplementation to receive the maximum benefit. Please do the research before you buy.
References:
1. Specificity of the neuroendocrine response to orgasm during sexual arousal in men. (2003) (http://joe.endocrinology-journals.org/content/177/1/57.full.pdf)
2. Norepinephrine stimulates arachidonic acid release from vascular smooth muscle via activation of cPLA2. (1998) (http://ajpcell.physiology.org/content/274/4/C1129)
3. Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism. (2013) (https://www.hindawi.com/journals/ije/2013/361895/)
4. Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms. (2004) (http://ajcn.nutrition.org/content/79/6/935.full)
5. Histamine-induced release of arachidonic acid and of prostaglandins in the peripheral vascular bed: mode of action. (1980)
6. Histamine-induced inositol phospholipid breakdown mirrors H1-receptor density in brain. (1983)
7. Effects of the novel antidepressant S-adenosyl-methionine on alpha 1- and beta-adrenoceptors in rat brain. (1989) (https://www.ncbi.nlm.nih.gov/pubmed/2559855)
8. S-adenosyl-l-methionine inhibits phosphoinositide metabolism in the rat brain synaptosomal suspensions. (1993)
9. Anti-inflammatory activity of S-adenosyl-L-methionine: Interference with the eicosanoid system. (1983)
10. Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-δ/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells. (2013)
11. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. (2003)
12. Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats. (1990)
13. The influence of fish oil diet and norepinephrine treatment on fatty acid composition of rat heart phospholipids and the positional fatty acid distribution in phosphatidylethanolamine. (1986)
14. Inclusion of thiamine diphosphate and S-adenosylmethionine at their chemically active sites.
15. Estrogen and progestin bioactivity of foods, herbs, and spices. (1998) (https://www.ncbi.nlm.nih.gov/pubmed/9492350) also link to full article (http://www.cancersupportivecare.com/estrogenherb.html)
16. Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury. (https://www.ncbi.nlm.nih.gov/pubmed/18188998)
17. Antioxidant status and reproductive hormones in women during reproductive, perimenopausal and postmenopausal phase of life. (2014) (https://www.ncbi.nlm.nih.gov/pubmed/25335378)
18. Progesterone Inhibits Mast Cell Secretion (2006) (http://journals.sagepub.com/doi/pdf/10.1177/039463200601900408)
19. Tryptophan metabolism, disposition and utilization in pregnancy (2015) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626867/)
20. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (2013) (http://)
21. Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity. (https://www.ncbi.nlm.nih.gov/pubmed/2177509)
22. Endocrine Disruptor Screening Program (EDSP) Estrogen Receptor Bioactivity (https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-estrogen-receptor-bioactivity)
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Very interesting post. Can someone with sufficient medical knowledge verify this?
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Hi nanna1, thanks for your research and welcome to the forum. What are the symptoms you had during your POIS cycles before you found this cure? Did all your symptoms stop within 1 month of taking the described stack?
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Hi paradoxx,
My symptoms were persistent headaches, sneezing, runny nose, fatigue, pain in my left ear, memory/concentration problems and lacking motivation. This lasted 5 to 8 days. Fortunate my job has flexible hours, because some days I couldn't go to work during the normal hours because I was out of it. My social life was in the dumps. I had tried everything herbal supplement, fasting (from food), exercise.
I had been taking B6, B9, B12 vitamins, fish oil, alpha-GPC and Aspirin with some success over several months. Very significant improvements but not cured. One day I added SAM-e and vitamin B1. Within 24, all symptoms when away. Then the next day the symptoms came back so I kept taking them and after some research added vitamin D3 and stopped taking Aspirin. I feel great now! No symptoms. Getting ready to go play some basketball with friends. These are all supplements that I found on other peoples POIS post that worked for them. Once I found out what worked for me I did the research to find out why. The only downside to the "cure" is I have to keep taking the supplements or else after a week or so the symptoms will come back.
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Hi nanna1,
Thanks for sharing your information. I am glad you have found empirical success in controlling your symptoms :)
It is not always possible to explain why what we take is effective, but I see you have taken the time to build a complete hypothesis about POIS pathophysiology. That's quite rare, usually people are not at ease enough with scientific articles and medical terminology to do so ( out of curiosity, are you working in a scientific field ?). Thanks for this great implication from your part, I know the kind of time investment needed to do this.
Some of the metabolic pathways you refer to has already been discussed and presented by forum members. For example, the methyl pathway and methylation problems have been discussed a lot by Kurtosis, a few years ago. The inflammatory cytokines production and AA pathways have been presented by myself, among others. However, your inclusion of the alpha-2 receptors is rather new. What led you to believe that the alpha1-adrenergic receptors are highly implicated in POIS ? I ask because strong stimulation of alpha1 receptors should cause high blood pressure. This manifests in some POIS sufferers, but not every one. And, in others, it is rather the opposite, it is hypotension that manifests ( and rather severe low blood pressure, in my case, when left untreated ). At any rate, like you may have read on the forum, I really think there is more than one type of POIS, with some different manifestations, but sharing a common pattern, so it is possible that one of these types implies the a1 receptors, but not the other types.
Your hypothesis is clearly on the neurologic side, with no mention of a possible prostate antigen ( like Waldinger is currently searching for). Once again, I think it is possible that there are both types of POIS, and even a third one, thinking about the hormonal factors. And, of course, a mix of all that is possible too. But there are at least some cases where there is more at play than just the neurology of orgasm. For example, there are POIS symptoms in members following a prostate leak caused by passing a large stool - no stimulation, no raise in neurotransmitters levels, just some prostatic liquid leaking in the urethra. Also, there are cases of anorgasmic ejaculations leading to POIS ( I, for one, had quite often anorgasmic ejaculations, and POIS is fully manifesting anyway, and have read similar reports by other members.... for me POIS should be called Post Ejaculatory Illness Syndrome, or PEIS.... ). Again, I am not again "pure neurological" POIS as a possibility, but would have to be a subtype of POIS.
Your stack of supplements reminds me a lot about what Kurtosis was taking for methyl cycle support. He also tried SAMe, but was linking its effectiveness to improved methylation of histamine ( he had a 23andme genetic test done, and based his explanations on that, in part. Did you have such a test done ? ). You can see an example of his own theory at http://poiscenter.com/forums/index.php?topic=783.msg7183#msg7183 . He had a very effective control of his symptoms, like you have too.
Some other members also report quite good results with Complex B vitamins, along the lines of your own stack ( but maybe minus the SAMe).
I did not tried SAMe myself, it is rather hard to find here, and is also quite expensive here. Since I have found an effective pre-pack composed of cheaper supplements, I have stopped at that and did not have to try SAMe.
Is there any particular reason why you advice to discontinue methylfolate ( B9) after a month ?
Also, quercetin, luteolin, and other mast cell stabilizers has been shown to be very useful and effective in my case and for other members as well. I read you seems to avoid them, linking them to negative effect on sperm mobility. Is it because you are in a relationship and try to have children ? Because otherwise, sperm motility is not that important, and those mast cells stabilizers are a good add-on against the effects of histamine, so can be quite useful in POIS. I do not write this to be critic, just to fully understand the reasons behind the opinions you express in your post.
Thanks again for sharing. I fully agree with your idea of posting about our results and ideas, so we receive feedback, and all together, improve our understanding of POIS.
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Hi Quantum,
Thanks for your detailed reply. As stated earlier, I wanted to open-source this stack so that others could build upon it, modify it, and improve it. I?m currently experimenting to find the optimum minimum dosages.
The POIS forums have been very helpful in researching the POIS cascade. I used them as a guide to find the mostly likely causes and remedies of the disease and searched the literature to validate some approaches and discard others. For example, my initial reason for looking into and trying the B vitamins came from success stories here (POIScenter) from members who used them. However, I found that not all of the B complex vitamins are needed to see improvements in POIS. I recommended staying away from concentrated extracts of quercetin, luteolin, etc.. because I would like to have children some day and need a stack that will allow me to continue to be fertile. But I do consume foods with those plant nutrients in them (apples, onions, green tea). Niacinamide (vitamin B3) is the strongest mast cell stabilizer that you can buy over the counter (https://www.ncbi.nlm.nih.gov/pubmed/57931) and is used in skin beauty products for that reason. Nicotinic acid has the opposite effect. I recommended discontinuing B9 after a month because long term folate supplementation is associated with increased cancer risk.
Background about me, I?m a postdoc working in the area of biomedical engineering. POIS is not my specialty area. My work/research focuses on gene regulation networks, receptor mediated gene expression, protein expression and their morphological consequences.
You were right to point out that there is more than one type of POIS disease. According to the above POIS cascade hypothesis there are at least 3 types of POIS (COX, LOX and CYP450 mediated) and 2 causes (alpha1-receptor, h1-receptor overexpression). All three of these types result from AA being metabolized by these enzymes. And depending on our individual relative genetic expression of the three classes of enzymes, we should each experience a unique mixture of the three diseases. This does not exclude there being other types of POIS and additional cause.
A map of COX and LOX from: Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms. (2004) http://ajcn.nutrition.org/content/79/6/935.full
(http://i.imgur.com/Ya5okLH.jpg)
I agree that inflammatory cytokines are downstream mediators of POIS. The initial focus for the stack was looking as far upstream as possible to get to the root cause. Since the elevation of norepinephrine is transient around the time of orgasm, the alpha1-adrenergic (a1A) receptor should only change blood pressure for a small window of time (reference #1 in above post). Histamine is a different story. As you and kurtosis have noted, histamine levels are brought down by SAM-e, and if SAM-e is depleted, the h1-histamine receptor can continue to be stimulated and modify blood pressure. So blood pressure may point to whether a1A or h1H is more of an individual?s problem. Thanks for bringing up the blood pressure issue. I had not thought about it before.
As it relates to stool passing causing POIS, may I suggest a plausible explanation; the seminal vesicle. It is important to consider that the seminal vesicle sits on top of the prostate and rest against the colon (https://en.wikipedia.org/wiki/Seminal_vesicle). As the stool passes through the lower colon, it will compress the seminal vesicle before reaching the prostate. The most abundant lipid in seminal fluid is phosphorylcholine (https://en.wikipedia.org/wiki/Semen#Human_semen), which, in the absence of sufficient methyl groups, is generated from PC in the lipid bilayer using a POIS Cascade type mechanism. So whenever seminal fluid is drawn through the prostate, the body will naturally try to replace methyl groups from lost phosphorylcholine. No orgasm (requiring dopamine) is needed to trigger the above POIS; just the contraction of the seminal vesicle (requiring norepinephrine). The main job of the prostate is to keep the bladder and seminal vesicle from leaking. However, if the prostate is leaking, it is likely that one or both of the other two are as well. Again this is just a suggestion open to debate.
I searched through the literature and found no mechanisms for antigen mediated POIS. The immune cells have access to the prostate. If there is enough antigen (or allergen) stored in the prostate to cause sickness, then I would expect the prostate would always be under attack by the immune system. I fully agree with the title rosscb used for the link you shared from kurtosis? post, ?The autoimmune theory is bogus?.
Thanks again Quantum for sharing your insights and experience. Since I am a new member of POIScenter this was very helpful. Some of your questions were challenging and intellectually stimulating. Hopefully, the community benefits from this and further discussions!
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Hi nanna1,
I am not surprised to learn that you work in biomedical engineering.
About the autoimmune hypothesis, the jury is still out on this one, and I still think it can be part of what causes POIS ( I was interested in Kurtosis post, in the thread I referred to, but not the OP opinion ;) ) . My view on this is based on the fact that, beyond the existence of a testicular/urethral blood barrier, there is the very low blood flow in the prostate tissue. This is well known, and explains why the antibiotic treatment for a bacterial prostatitis can last for as long as three months - the active ingredient penetrate very slowly in the prostate tissue, as well as the white blood cells that should have get rid of the infection in the first place. So, it could be possible that the sudden and heightened exposure to prostatic fluid and a potential prostatic antigen in it, following ejaculation, could trigger an auto-immune reaction otherwise not possible.
But, as we already know, POIS medical study will be necessary to test those hypothesis, be it the neurological, the immunological or hormonal hypothesis.
The fact that niacin is a very good mast cell stabilizers could explain why there are so many empirical success among members with it. However, POIS is very complex, and for some unknown reasons, a significant proportion of members have no relief with niacin ( hence my "POIS types chart", with many possible subtypes, based on specific relief methods).
Your explanation about POIS vs passing stool is well constructed, and is in line with my own opinion, that is, a local reaction occurs, in opposition to other general explanations of POIS that rely on the neurotransmitters variations in the brain during orgasm, exclusively. So, either the local event is from prostatic or seminal glands fluid, I am at ease with that. But I wouldn't subscribe to a "brain-only triggering event " theory.
For further discussion, if you are interested, how would you tackle the "clusters of symptoms" problem, in your general hypothesis of POIS ? In a given POIS sufferer, the symptoms are quite stable from one episode to the other. But from one POIS sufferer to the other, some clusters may be present of absent. For example, some have the "allergy-like" symptoms ( itchy eyes, sneezing, rashes, etc...) some not, and never had them. Also, most have both cognitive and emotional symptoms ( cognitive impairment, and, personality and mood change, and not for the better....). But in some case, like in myself and some others, I have much emotional symptoms, but absolutely no cognitive symptoms. That's yet another "POIS riddle". There is of course a question of personal reaction and genetics, maybe, common chain of event, but such difference is quite questioning. I would be interested on your opinion on this ( you may already have read, or not, my own view on this, but as you said, different points of view makes for a better overall vision ).
Thanks for this discussion!
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Hi nanna1,
Thank you for an very insightful write-up! I am glad that your regimen works very well for you.
I wonder if you could shed some light on some questions.
1. How many "o" per week can you have these days without any pronounced symptom? I assume that you are no longer on methylfolate supplements.
2. when you lift weight or exert yourself for 30+ mins, do you have a lite version of POIS-like symptoms?
From my personal experience, 5-HTP supplementation + IDO/TDO inhibitors are very important in my stack. Taking NSAID alone (blocking COX-1/2) is not sufficient.
3. Any lead on how α1A and H1A may trigger IDO/TDO upregulation?
From my past discussion with Quantum, I think there is a large component of Mast Cell Activation in POIS, sometimes also called Mast Cell degranulation induced pseudoallergy. Many NSAID (aspirin, ibuprofen) actually activate mast cells more, e.g. in "aspirin induced asthma". I am taking celecoxib as needed because it also inhibits ALOX-5 and limits leukotriene production. Quercetin, Curcumin also help in these areas.
4. If a1A and h1H receptors were the main reasons, why not take a selective α1-adrenergic receptor antagonist or an alpha blocker, and a H1 antihistamine 30mins before your O. I wonder if you have tried that. On paper alpha blocker + h1 antihistamine would solve all the problems in your case, since they arrest the process from the very beginning?
Thanks!
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Hi Romies,
Thank you for your question and comments. I number the responses to make sure I address all your questions. Please let me know if this is helpful or if you have any suggestions.
- Currently I O about twice a week. I don?t have any symptoms of POIS that I am aware of. Sometimes I feel really tired and sleep immediately following (probably low dopamine). But after a quick nap, I feel fine. I noticed that the day after, I am super motivated. I still take the supplement stack daily as described above.
- Lifting weights for me used to cause fever, sneezing and runny nose. Not as bad as orgasm though, which for me would include all of the above symptoms plus really bad headache and joint pain in random places. Vitamin B complex drastically reduced my exercise induce sickness. But I wasn?t healed of POIS until I introduced SAM-e and Benfotiamine (fat soluble vitamin B1).
- Romies, to be honest with you, before your question, I hadn?t looked into IDO/TDO. But I did a quick literature search and here is what I found. Both a1A and h1H upregulate IDO/TDO through the COX-1/2 enzymes. More specifically, (a1A & h1H)->Arachidonic Acid (AA)->COX->prostaglandin E2 (PGE2)->Interferon-γ-> IDO/TDO gene expression (please see references below) [1, 2]. Three of the supplements currently in the POIS Cascade stack suppress IDO/TDO usage and kynurenine production (vitamin D3, vitamin B6 and EPA).
- Vitamin D3 downregulates IDO/TDO expression by two independent methods. D3 blocks COX-1/2, and D3 blocks the genetic transcription of the Interferon-γ gene on the DNA itself [3].
- EPA (omega-3 fatty acid) blocks AA production, blocks AA incorporation into phosphatidylcholine (PC and phospholipid bilayer) and blocks AA access to COX/LOX/CYP450 enzymes.
- Vitamin B6 (along with other protein enzyme) converts tryptophan into serotonin. Another way of thinking about it is, B6 diverts tryptophan away from the IDO/TDO enzymes (tryptophan->IDO/TDO-> kynurenine) [5]. Which leads to a reduction in kynurenine [6]. Moreover, B6 accelerates the removal of kynurenine from the body by preventing the downregulation of the enzyme that removes kynurenine [7]. (please see figure below)
(http://i.imgur.com/rZj36Vw.png)
Both D3 and EPA are fat soluble, so it may take a month of consistent supplementation to see their full effects. B6 is water soluble and should kick-in within a couple of days. Many of the supplements in the POIS Cascade Stack have slow diffusion across the blood/brain barrier and/or slow incorporation into the phospholipid bilayer. So it could take 3 to 4 weeks of consistent supplementation before the effects can be assessed. I personally have not tried IDO/TDO inhibitors, so any knowledge on prescription medications may best be addressed by a health healthcare professional.
Mast cells have a dedicated pair of receptors that specifically detect niacinamide and nicotinic acid. Dietary niacinamide is probably the most potent inhibiter of mast cell activation that you can find for two reason. First, niacinamide alone has higher bioavailability than polyphenols like quercetin and curcumin which require black pepper extract to enhance their bioavailability. Second, niacinamide is one of the body?s own endogenous inhibitors of mast cell activation. The receptors for nicotinic acid have the opposite effect and cause niacin-flush (selective mast cell release). I have one warning about directly inhibiting mast cells. Mast cell activation is a natural part of orgasm (even for non-POIS people) and is required for ejaculation. Attenuation will necessarily lead to reduced ejaculate volume. I experienced this personally with curcumin, luteolin and niacinamide. The reason I stopped trying to directly inhibit mast cells is that I plan to impregnate my future wife and I want as much ejaculate as possible. My person preference of course, has nothing to do with the POIS disease or the pleasure of orgasm. With that said, I do not wish to discourage you or any others, who may have different goals than my own, from using mast cell inhibitors.
- 4. You are right, in theory drugs that block a1A and h1H should stop POIS. I have not tried any a1A inhibitors, but I have tried h1H inhibitors (Benadryl, Claritin, Allegra) with a lot of success. Benadryl worked the best; no sneezing, runny nose, joint pain or watery eyes. However, Benadryl has a lot of side effects; long-term use is associated with dementia. Claritin and Allegra were okay. Allegra has almost no side effects. But none of the h1H blockers completely got rid of my POIS headaches. Moreover, when I stopped taking the h1H inhibitors there seemed to be a rebound in the receptors. Once the drug wore off, I was even more sensitive to allergens like pollen than before. This ?rebound? happened with all three (Benadryl, Claritin, Allegra). From my experience, unless it addresses a root cause of POIS, a drug (or herb) that solves one problem will inevitably create others. But when you don?t know the root cause and you need short-term relief, definitely try anything that helps.
1. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation (2017)
2. Interferon-gamma ? Inducible Inflammation: Contribution to Aging and Aging-Associated Psychiatric Disorders (2011)
3. Interferon-γ Regulates the Proliferation and Differentiation of Mesenchymal Stem Cells via Activation of Indoleamine 2,3 Dioxygenase (IDO)
4. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. (1998)
5. Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan. (2006)
6. A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites. (2013)
7. https://en.wikipedia.org/wiki/Kynurenine_pathway#Acquired_and_inherited_enzyme_deficiencies
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I did not tried SAMe myself, it is rather hard to find here, and is also quite expensive here. Since I have found an effective pre-pack composed of cheaper supplements, I have stopped at that and did not have to try SAMe.
Walmart Canada sells SAMe online at a pretty low cost. I am just thinking that SAMe could be an addition to your NE-morning-after stack. I noticed nanna1's stack does not have to be timed to his O's.
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Hello nanna,
Thanks for your impressive work.
I've been thinking for a while now that POIS was psychologically rooted mainly because my personnal history could easily explain it.
I've got a lot of help from meditation and as long as I keep my anxiety level low, POIS symptoms are managable.Symptoms are also almost absent when I am in vacation. Moreover, sometime I get symptoms (exhaustion, confusion, etc without orgasm while I can be symptoms free after an orgasm.
I've also had for years really usefull help with propanolol a beta blockers which inhibit sympathetic nervous system.
So it appears that-at least in my case but not only- the state of my nervous system(sympathetic = anxiety vs parasympathetic = calmness) has a major influence on the severity and duration of symptoms.
I still feel that there is a disregulation somewhere happening after orgasm and anxiety itself doesnt seems to explain everything.
Is your theory can articulate with what I describe above ?
Thanks a lot
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Hi nanna1,
Thank you for your detailed reply. You clearly have thought a lot and done your research.
2. Lifting weights for me used to cause fever, sneezing and runny nose. Not as bad as orgasm though, which for me would include all of the above symptoms plus really bad headache and joint pain in random places. Vitamin B complex drastically reduced my exercise induce sickness. But I wasn?t healed of POIS until I introduced SAM-e and Benfotiamine (fat soluble vitamin B1).
I am curious here if your exertion-induced symptoms were also most severe 8-10 hrs after your exertion, and lasted for 1-2 days. That was my experience.
Romies, to be honest with you, before your question, I hadn?t looked into IDO/TDO. But I did a quick literature search and here is what I found. Both a1A and h1H upregulate IDO/TDO through the COX-1/2 enzymes. More specifically, (a1A & h1H)->Arachidonic Acid (AA)->COX->prostaglandin E2 (PGE2)->Interferon-γ-> IDO/TDO gene expression (please see references below) [1, 2]. Three of the supplements currently in the POIS Cascade stack suppress IDO/TDO usage and kynurenine production (vitamin D3, vitamin B6 and EPA).
I am familiar with the PGE2-Interferon-γ pathway. I was wondering if there is any other direct pathway.
- Vitamin D3 downregulates IDO/TDO expression by two independent methods. D3 blocks COX-1/2, and D3 blocks the genetic transcription of the Interferon-γ gene on the DNA itself [3].
- EPA (omega-3 fatty acid) blocks AA production, blocks AA incorporation into phosphatidylcholine (PC and phospholipid bilayer) and blocks AA access to COX/LOX/CYP450 enzymes.
- Vitamin B6 (along with other protein enzyme) converts tryptophan into serotonin. Another way of thinking about it is, B6 diverts tryptophan away from the IDO/TDO enzymes (tryptophan->IDO/TDO-> kynurenine) [5]. Which leads to a reduction in kynurenine [6]. Moreover, B6 accelerates the removal of kynurenine from the body by preventing the downregulation of the enzyme that removes kynurenine [7]. (please see figure below)
Both D3 and EPA are fat soluble, so it will take about a month of consistent supplementation to see their full effects. B6 is water soluble and should start to kick-in within a couple of days. Romies, my recommendation would be to either supplement with these 3 or the entire POIS Cascade stack for a month (while continuing with your other meds). And then slowly wean off both 5-HTP and IDO/TDO inhibitors over the course of a week while continuing the stack. I personally haven?t tried IDO inhibitors so I don?t know how the weaning process will work. You could be the first to find out!
I am glad that Vitamin D3 and EPA worked for you to block COX/LOX, but they are not enough for me.
I have been taking daily supplement of the following for more than 5 years, years before I tried Quantum's prepack.
Methylguard (methylfolate 400mcg; methylcobalamin 400mcg; Trimethylglycine 600mg)
Vitamin D (4000IU)
Vitamin B6 5mg
Zinc 10mg (from Zinc Mono-L-methionine)
Mg 150mg (from Magnesium Aspartate)
EPA (410mg) + DHA(274mg)
These were not enough for me. Without Quantum's prepack, I will still get a 2-day POIS hell.
I am still taking the stack above daily for other reasons, as suggested by my blood lab report.
I have not tried such a high EPA dose. I will give it a try with concentrated EPA/DHA, together with ALA, to really suppress AA synthesis.
The pre-pack is used as a one-time as-needed dose. So there is not much weaning here, fortunately. I sometimes go on 2 weeks without having an O or needing a prepack when I am busy/traveling.
Mast cells have a dedicated pair of receptors that specifically detect niacinamide and nicotinic acid. Dietary niacinamide is probably the most potent inhibiter of mast cell activation that you can find for two reason. First, niacinamide alone has higher bioavailability than polyphenols like quercetin and curcumin which require black pepper extract to enhance their bioavailability. Second, niacinamide is one of the body?s own endogenous inhibitors of mast cell activation. The receptors for nicotinic acid have the opposite effect and cause niacin-flush (selective mast cell release). I have one warning about directly inhibiting mast cells. Mast cell activation is a natural part of orgasm (even for non-POIS people) and is required for ejaculation. Attenuation will necessarily lead to reduced ejaculate volume. I experienced this personally with curcumin, luteolin and niacinamide. The reason I stopped trying to directly inhibit mast cells is that I plan to impregnate my future wife and I want as much ejaculate as possible. My person preference of course, has nothing to do with the POIS disease or the pleasure of orgasm. With that said, I do not wish to discourage you or any others, who may have different goals than my own, from using mast cell inhibitors.
Again, I think you are a lucky man, in that niacinamide works for you. I have tried before without success, with 1500mg niacinamide a few hours before an O, and had no success in reducing POIS symptoms. Niacinamide has a serum half-life of 6-7 hrs, so it should have still been in my system when I had an "O".
If you want to increase ejaculate size, there are some other supplements that reportedly work very well.
https://www.thundersplace.org/male-supplements/holy-grail-of-cum-load-increase.html
4. You are right, in theory drugs that block a1A and h1H should stop POIS. I have not tried any a1A inhibitors, but I have tried h1H inhibitors (Benadryl, Claritin, Allegra) with a lot of success. Benadryl worked the best; no sneezing, runny nose, joint pain or watery eyes. However, Benadryl has a lot of side effects; long-term use is associated with dementia. Claritin and Allegra were okay. Allegra has almost no side effects. But none of the h1H blockers completely got rid of my POIS headaches. Moreover, when I stopped taking the h1H inhibitors there seemed to be a rebound in the receptors. Once the drug wore off, I was even more sensitive to allergens like pollen than before. This ?rebound? happened with all three (Benadryl, Claritin, Allegra). From my experience, unless it addresses a root cause of POIS, a drug (or herb) that solves one problem will inevitably create others. But when you don?t know the root cause and you need short-term relief, definitely try anything that helps.
For me, the daily Methylguard (methylfolate 400mcg; methylcobalamin 400mcg; Trimethylglycine 600mg) cleared the histamine in my body effectively. I used to need daily Zyrtec for nasal allergy before I tried Methylguard, but I don't need Zyrtec any more with Methylguard.
I suspect that your subtype of POIS is somewhat different from mine, because Zyrtec/Claritin/Allegra never gave me cognitive/mood relief from POIS.
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Regarding the effects of Curcumin, Quercetin on sperm motility
The papers that says curcumin reduces sperm motility were largely performed NOT with oral-intake of curcumin. Instead, curcumin was mixed into semen directly. See the following discussion:
http://natural-fertility-info.com/fertility-health-clearing-up-confusion-about-turmeric-as-birth-control.html
https://www.ncbi.nlm.nih.gov/pubmed/21337449
And there are other study showing curcumin beneficial for sperm quality
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312379/
https://www.ncbi.nlm.nih.gov/pubmed/25149981
So maybe the jury is still out there.
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I did not tried SAMe myself, it is rather hard to find here, and is also quite expensive here. Since I have found an effective pre-pack composed of cheaper supplements, I have stopped at that and did not have to try SAMe.
Walmart Canada sells SAMe online at a pretty low cost. I am just thinking that SAMe could be an addition to your NE-morning-after stack. I noticed nanna1's stack does not have to be timed to his O's.
Hi Romies,
Indeed, I have checked on walmart.com and prices are getting lower than a few years ago ( not on walmart.ca, though...). I have also checked on vitacost.com, my preferred source for supplements not available in Canada, and prices for SAMe are lower there as well.
I saw there are mainly 200mg and 400mg forms, and some are enteric coated.
Nanni, it would be of interest for the members here to know if the 200mg SAMe tablets you have been using are regular tablets or enteric coated tablets, and to confirm that your total daily dose is 200mg.
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2. Lifting weights for me used to cause fever, sneezing and runny nose. Not as bad as orgasm though, which for me would include all of the above symptoms plus really bad headache and joint pain in random places. Vitamin B complex drastically reduced my exercise induce sickness. But I wasn?t healed of POIS until I introduced SAM-e and Benfotiamine (fat soluble vitamin B1).
Very interesting, Nanni. Last year, we had a thread about "pseudo-POIS" symptoms after physical exercise. Romies has this problem, and I have too (mostly marked fatigue, and my recovery period is abnormally long - but not all the other usual POIS symptoms I have ). I take a simpler version of my pre-pack before sport, that includes the same omega-3 source ( 600mg EPA/300mg DHA), some anti-oxidants too. I also take potassium and some other supplements after sport ( but potassium seems to be linked to a very personal condition, I seem to be the only one to have good results with it, be it for POIS or after sport).
It is clear that no semen production is implied in sport ( I enjoy sport, but not that much...hehe...), so this is where your hypothesis about AA production following high norepinephrine levels could be a good explanation.
I hope the upcoming team that will receive our research grant for a POIS study will tackle such subjects as inflammatory cascades and metabolic changes in POIS. For now, all we have is some empirical success, and we have to deduct what is really going on from what has brought some relief.
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I saw there are mainly 200mg and 400mg forms, and some are enteric coated.
According to Examine.com https://examine.com/supplements/s-adenosyl-methionine/#summary2-0
enteric coated capsules increases bio-availability by ~3x.
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---eicosapentaenoic acid, EPA (1000mg) [AA synthesis inhibitor, AA blocker]
---docosahexaenoic acid, DHA (260mg) [AA synthesis inhibitor]
Just noticed that your daily intake of EPA+DHA is 3x of what I am typically taking. I will try this for 60 days and report my findings.
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2. Lifting weights for me used to cause fever, sneezing and runny nose. Not as bad as orgasm though, which for me would include all of the above symptoms plus really bad headache and joint pain in random places. Vitamin B complex drastically reduced my exercise induce sickness. But I wasn?t healed of POIS until I introduced SAM-e and Benfotiamine (fat soluble vitamin B1).
Very interesting, Nanni. Last year, we had a thread about "pseudo-POIS" symptoms after physical exercise. Romies has this problem, and I have too (mostly marked fatigue, and my recovery period is abnormally long - but not all the other usual POIS symptoms I have ). I take a simpler version of my pre-pack before sport, that includes the same omega-3 source ( 600mg EPA/300mg DHA), some anti-oxidants too. I also take potassium and some other supplements after sport ( but potassium seems to be linked to a very personal condition, I seem to be the only one to have good results with it, be it for POIS or after sport).
What is your baseline daily EPA/DHA intake besides the pre-packs?
Here is some good reading with referenced summary (page 48, 49): https://books.google.com/books?id=v6fuDQAAQBAJ&lpg=PA1&dq=enteroimmunology&pg=PA48#v=onepage&f=false
My take away is
1. Flaxseed oil does not work, since ALA supplementation does not suppress AA formation. see graph on page 46
also flaxseed oil oxidizes way too fast.
2. Oliver oil is good, with low LA load. Just need to be taken with fish oil.
3. It takes 60 days for EPA to reach steady state in ones body.
4. If our COX, ALOX, a1a, H1a are too trigger happy, we may need to be aggressive on EPA/DHA. So I am looking at 2 gram/day in take. That would reduce DOMS too.
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What is your baseline daily EPA/DHA intake besides the pre-packs?
Here is some good reading with referenced summary (page 48, 49): https://books.google.com/books?id=v6fuDQAAQBAJ&lpg=PA1&dq=enteroimmunology&pg=PA48#v=onepage&f=false
My take away is
1. Flaxseed oil does not work, since ALA supplementation does not suppress AA formation. see graph on page 46
also flaxseed oil oxidizes way too fast.
2. Oliver oil is good, with low LA load. Just need to be taken with fish oil.
3. It takes 60 days for EPA to reach steady state in ones body.
4. If our COX, ALOX, a1a, H1a are too trigger happy, we may need to be aggressive on EPA/DHA. So I am looking at 2 gram/day in take. That would reduce DOMS too.
Hi romies,
I took, in the past, EPA/DHA daily for many years, at around 400mg EPA/200mg DHA once or twice daily. But a few years ago, when I turned to the "pre-pack" strategy, I stopped daily uptake of omega-3. It ends up now that I take them around 2 to 3 times a week anyway, because my 600/400 capsules are part of both my sport pre-pack and my POIS pre-pack.
Regarding Flaxseed oil capsules, my reason for including them in my pre-pack is for the lignans in them, which are good antioxidants, and, mainly, have NMDAr blocking properties, so they protect against excitotoxicity, and thus reduces the POIS-induced anxiety and other CNS symptoms.
I do not consider flaxseed to be the most important part of my pre-pack, but who knows. I could try only one capsule of flaxseed instead of 2, in my POIS pre-pack, and 2 capsules of omega-3 instead of one. I did not made many changes or many new tests in the last two years.... if it's not broken, don't fix it ;)
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Hi All,
Here is how I source my stack:
- NOW SAMe 200 mg,60 [enteric coated] Tablets (https://www.amazon.com/NOW-SAMe-200-60-Tablets/dp/B0013OW3V6/ref=sr_1_21_s_it?s=hpc&ie=UTF8&qid=1501024535&sr=1-21&keywords=sam-e)
- Nature Made Vitamin D3 2000 IU, Value Size, 220-Count (https://www.amazon.com/Nature-Made-Vitamin-Value-220-Count/dp/B004U3Y8NI/ref=sr_1_6_s_it?s=hpc&ie=UTF8&qid=1501024866&sr=1-6&keywords=d3&th=1)
- NOW Alpha GPC 300 mg,60 Veg Capsules (https://www.amazon.com/NOW-Alpha-GPC-300-Capsules/dp/B001RYKA3U/ref=sr_1_5_s_it?s=hpc&ie=UTF8&qid=1501024705&sr=1-5&keywords=alpha%2Bgpc&th=1)
- Life Extension Mega Benfotiamine, 120 capsules (https://www.amazon.com/Life-Extension-Mega-Benfotiamine-capsules/dp/B000OSIO9W/ref=sr_1_2_s_it?s=hpc&ie=UTF8&qid=1501024996&sr=1-2&keywords=mega%2Bbenfotiamine%2B250%2Bmg&th=1)
- Nordic Naturals - EPA Xtra, Promotes Mood and Heart Health, and Optimal Immune Function, 60 Soft Gels (https://www.amazon.com/gp/product/B002CQU4Z6?ref_=sr_1_3_a_it&qid=1501023857&sr=8-3&keywords=EPA&pldnSite=1&th=1)
- OmegaVia EPA 500. Pharmaceutical Grade EPA Omega-3. Triglyceride-form EPA-only formula, 120 Capsules. 500 mg EPA per pill (https://smile.amazon.com/OmegaVia-Pharmaceutical-Omega-3-Triglyceride-form-Capsules/dp/B00D37S0HC/ref=sr_1_4_a_it?ie=UTF8&qid=1501040461&sr=8-4&keywords=epa)
Update/disclosure:
- I know I mentioned that I only supplement SAM-e once a day, but on O days I sometimes supplement a second time.
- I have increased my EPA (omega 3) supplementation to three times a day.
- Also, I drink a ?5-hour energy? drink two or three times a week to stay alert at work. It is my substitute for coffee since I do not drink coffee. I do not consider 5-hour energy as part of my stack because I drink it so rarely, but it does include B-vitamins and choline (methyl donor). So I thought I should mention that.
I am looking for a cheaper source of alpha-GPC (choline). Maybe a bulk power. If find one please let me know. [Choline bitartrate messes up with my stomach.]
Thanks Romies for sharing that link on volume from Thunderplace. I might get some zinc arginine. Quantum, I thought your joke about liking/not-liking sports was LOL. There was a lot of good discussion and ideas from yesterday and today. I may not know the answers to some of the things that were brought up, but there was a question from Lapoisse about non-O stress related POIS-like symptoms. Since Quantum also found that managing stress helped control POIS (My method for prevention and control of my POIS symptoms - 80% to 100% effective), I thought I would do some digging. It seems like Quantum was really on to something with the NMDA inhibitors in his pre-stack.
Stress up regulates histamine production in mast cells [1], and it up-regulates NMDA receptors (NMDAR, glutamate receptor) throughout the brain [2, 3]. Stress hormones like cortisol up-regulate the number of NMDAR through the glucocorticoid receptor [3]. Stimulation of NMDAR by glutamate causes the release of Arachidonic Acid (AA) from the phospholipid bilayer in the same way that alpha1-adrenergic (a1A) and h1-histamine (h1H) do; through activation of the enzyme Phospholipase A2 [4, 5]. The title of this article is worth noting: [NMDA receptors activate the arachidonic acid cascade system in striatal neurons. (1988)]. It is believed that abnormal NMDAR-mediated AA release is at least partly associated with inflammatory brain diseases. For example, mania and bipolar drugs like lithium, carbamazepine and valproate all inhibit Phospholipase A2 (and AA release) [6, 7]. The anti-depressant, lamotrigine, also inhibits Phospholipase A2 [6]. Antipsychotics, olanzapine and clozapine inhibit Phospholipase A2 (and AA release) [7]. In the following article, they note that COX mediated inflammation is decreased with all of these drugs: [Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade. (2014)] Each of these drugs have other therapeutic effects specific to the diseases that they treat, but the one common benefit is inhibition of NMDAR->AA mediated inflammation.
With that said, things get more complicated from here, because, like the adrenergic and histamine receptors, there are different NMDAR subtypes (NR1, NR2A, NR2B, NR3A, etc?). They each have different responses to different agonist and antagonist, and I am not sure which ones are associated with abnormal AA release/inflammation. It is known that glucocorticoids like cortisol down-regulate NR2A-NMDAR and up-regulate NR2B-NMDAR signaling [8]. While niacinamide (vitamin B3) has the reverse effect up-regulating NR2A-NMDAR and down-regulating NR2B-NMDAR. Agmatine Sulfate (which you can find on Amazon.com or GNC) is a pretty strong inhibitor of NR1-NMDAR, which might be helpful since AA & histamine themselves are enhancers of NR1 activation. (see figure below [9])
(http://i.imgur.com/QH9OP6G.png)
Final note: It appears that stress hormones are what cause the NMDA receptors to become overexpressed and lead to abnormal inflammation. If we could keep those hormones in check, that would prevent the AA cascade. But this is the limit of my knowledge on the stress related aspect of a POIS cascade-like hypothesis. I found Quantum?s post that I referenced above useful looking at way to combat this. He includes some NMDAR blockers and several techniques of managing/reducing stress.
1. Acute stress modulates the histamine content of mast cells in the gastrointestinal tract through interleukin-1 and corticotropin-releasing factor release in rats. (2003) (http://www.pnas.org/content/106/33/14075.full.pdf)
2. Stress-Induced Changes of Hippocampal NMDA Receptors: Modulation by Duloxetine Treatment (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037916)
3. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory (2009) (http://www.pnas.org/content/106/33/14075.full.pdf)
4. NMDA receptors activate the arachidonic acid cascade system in striatal neurons. (1988)
5. NMDA receptor-mediated arachidonic acid release in neurons: role in signal transduction and pathological aspects. (1992)
6. Mood-stabilizers target the brain arachidonic acid cascade. (2009)
7. Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade. (2009)
8. Glucocorticoid Rapidly Enhances NMDA-Evoked Neurotoxicity by Attenuating the NR2A-Containing NMDA Receptor-Mediated ERK1/2 Activation (2010)
9. Allosteric Receptor Modulation in Drug Targeting (2006)
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Hey nanna1,
I've just read over your ideas on the inflammatory cascade involved in POIS and found it very informative. I'll have to read further into these concepts, I'm also in the biomedical field and I've read a little about COX and AA pathways, a lot about histamine, methyl groups, and NDMA receptors, but not much about alpha-1-receptors, and your posts tie them all together very well.
I searched through the literature and found no mechanisms for antigen mediated POIS. The immune cells have access to the prostate. If there is enough antigen (or allergen) stored in the prostate to cause sickness, then I would expect the prostate would always be under attack by the immune system. I fully agree with the title rosscb used for the link you shared from kurtosis? post, ?The autoimmune theory is bogus?.
I have a small correction to make to this as it's important to my theory of POIS. Quantum correctly stated earlier in this thread that white blood cells do not really reach the prostate, and most immune cells do not have access to the prostate. The study "A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium" showed diffuse leukocyte infiltration and very restricted inflammatory cell penetrate into the prostate in rats, although the blood-prostate barrier in humans is referenced in several other publications.
Quantum also asked a very good question: "So, it could be possible that the sudden and heightened exposure to prostatic fluid and a potential prostatic antigen in it, following ejaculation, could trigger an auto-immune reaction otherwise not possible." Yes, this is possible, and occurs in men with chronic prostatitis, as reported in the study "Autoimmune prostatitis: Evidence of T cell reactivity with normal prostatic proteins". Furthermore urinary tract infection is a proven cause of autoimmune disease, with molecular mimicry and cross-reactivity proposed as the reason for the production of auto-antibodies, from the study "Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection". These concepts, along with the presence of leukocytes in my urine following POIS, has led me to my theory that POIS is an infection of an immune privileged/"sanctuary site" of the urinary tract with a microorganism that exhibits molecular mimicry to normal human antigens. I believe it to be a subset of chronic prostatitis, which researchers termed autoimmune prostatitis in one of the studies listed above. Chronic prostatitis is a common syndrome that researchers believe is caused by a microorganism, which I think is likely fungi in most POIS sufferers due to our symptoms. Below is the abstract of "Current treatment options in the management of chronic prostatitis", take a look at what is the first proven treatment listed.
"Chronic prostatitis is a disease with an unknown etiology that affects a large number of men. The optimal management for category III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unknown. The recent years have seen a significant increase in research efforts to understand, classify and treat CP/CPPS. Standard treatment usually consists of prolonged courses of antibiotics, even though well-designed clinical trials have failed to demonstrate their efficacy. Recent treatment strategies with some evidence of efficacy include: alpha-blockers, anti-inflammatory agents, hormonal manipulation, phytotherapy (quercetin, bee pollen), physiotherapy and chronic pain therapy. A stepwise, multimodal approach can be successful for the majority of patients who present with this difficult condition."
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Hi TrustTheProcess,
Thanks for commenting on the POIS cascade hypothesis and for taking the time to explain some details important to the Autoimmune Theory. I regret writing the sentences you show quoted from my July 24th post. I understand that people can be different and have different causes for their sickness. After so many years of suffering with a debilitating POIS, I am really excited and energized to share how I got cured (maybe too excited). I just want people cured, and I believe if we listen to our bodies and seek our greatest relief, we can all be our greatest fullest selves!
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Very interesting discussion !
Thanks to Romies for the info about the enteric coated SAMe capsules.
Thanks TTP for his well-researched perspective on chronic prostatitis.
Thanks to nanni too, for his thorough and referenced discussion about the possible role of NMDA receptors in POIS. Your references made clearer for me the link between the NMDAR activation and the AA neurotoxicity.
Stress management is good for about any health issue, and POIS is no exception, from my experience. To add to your excellent explanation, I would mention that cortisol upregulates the TDO enzyme in the liver which further divert the tryptophan metabolism toward neurotoxic kynurenine products, diminishing at the same time the production of the most useful serotonin and niacin ( see at http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory )
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I?m looking for a cheaper source of alpha-GPC (choline). Maybe a bulk power. If find one please let me know. [Choline bitartrate messes up with my stomach.]
Have you considered using lecithin, which is cheap, and a good source of phosphatidylcholine ?
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Hi,Nanna1 :)
In advance I ask to excuse me for my English. I've read your theory about POIS. And I had questions:
1 How long has your treatment helped you?
2 You said that in a month you should stop taking B9. But how to do it if it is included in the SAM?
thank you,Rinat
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Quantum and nanna1, thanks for the EPA/DHA dosage. I am going to give high-dose EPA/DHA a try for 60 days and see how my POIS and exercise-induced fatigue may change.
nanna1, thanks for sharing your list of supplements. We are using many of the same brands.
On NDMA's role in AA release, there was one trial before by another forum member: https://poiscenter.com/forums/index.php?topic=2092.msg18484#msg18484
who gave memantine a try, but did not find much benefit.
I understand he could be on a different sub-type of POIS, and not related to NDMA. But many others could be still NDMA related. Just wondering if anyone has shown great response to memantine or other meds.
BTW, the first week on memantine is well known to cause brain fog etc, and is similar to the cognitive symptoms of POIS itself.
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Regarding Flaxseed oil capsules, my reason for including them in my pre-pack is for the lignans in them, which are good antioxidants, and, mainly, have NMDAr blocking properties, so they protect against excitotoxicity, and thus reduces the POIS-induced anxiety and other CNS symptoms.
I do not consider flaxseed to be the most important part of my pre-pack, but who knows. I could try only one capsule of flaxseed instead of 2, in my POIS pre-pack, and 2 capsules of omega-3 instead of one. I did not made many changes or many new tests in the last two years.... if it's not broken, don't fix it ;)
That's quite interesting. I think the flaxseed oil I bought does not have much lignan in them. Lignan is a phytoestrogen, so I probably won't take a high dose.
Well, I see no harm at your dose of EPA/DHA. Very much agreed on "if it's not broken, don't fix it".
From month to month, I oscillate between adding supplements to my stacks and simplify them. I am in the adding mode right now, and probably will go into a subtraction mode in 3 months. lol
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Thanks Quantum for the Lecithin recommendation. I was taking a daily Lecithin-betaine combo about a year ago and it was beneficial. But I really like alpha-GPC?s near 100% bioavailability. But if I cannot find a cheaper source, I may give Lecithin another try.
To All, I highly recommend this article from Psychology Today on AA, DHA and EPA, which explains how to get the most out of an omega-3 supplement.
[What Are the Real Differences Between EPA and DHA? To reduce cellular inflammation, you need more EPA than DHA.] (https://www.psychologytoday.com/blog/in-the-zone/201204/what-are-the-real-differences-between-epa-and-dha)
P.S. The half-life of EPA in the body is roughly between 1.5 - 3 days depending on which form you buy, but it should not matter with daily supplementation. (must be taken with food)
Relating to stress management, there is a really interesting 2010 study on lowering cortisol. Apparently, casual social interaction is a great way for men to lower cortisol/stress hormones unless it is with a woman that you find sexually attractive [1]. LOL!
(click to enlarge image)
(http://i.imgur.com/jmJtfda.png)
For those interested in receptor blockers of (norepinephrine, histamine, glutamate), it seems like you would have to take them before the orgasm to get any relief from POIS. I found this out from personal experience back when I used to take allergy meds (h1-histamine blocker). I used to wait until after I felt sick to take the h1H blocker, and it didn?t help me much. Then one day I took Claritin ~2 hour before the O and got partial (but not full) relief. The below study seems to suggest that alpha1 blockers must be taken before the O, because norepinephrine mediated AA release and enzyme up-regulation happens in a short window around the time of the O [2]. (legend: white squares->men watching a boring documentary; black quares->men watching a different type of film while administering self-coitus; time units=minutes)
(click to enlarge image)
(http://i.imgur.com/43RWkMg.png)
If there is not enough methyl donors to degrade histamine, h1H might continue to cause problems. But other than that, there shouldn?t be much receptor stimulated AA release 5 min after O. Fatty acids like AA, on the other hand, and its enzymatic byproducts tend to have longer half-lives. Assuming you forgot to take your supplements that day, the only inhibitors that might work after an orgasm are COX/LOX/CYP450 enzyme inhibitors (taken before sickness starts).
Things are starting to pick-up at work. I am preparing to write a paper and apply for a research fellowship (unrelated to POIS). So I may not reply to the forum as often as I would like. Please forgive me if I do not reply in a timely manner.
1. Contact with attractive women affects the release of cortisol in men (2010)
2. Specificity of the neuroendocrine response to orgasm during sexual arousal in men (2003)
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Hi Nanna,
Thanks for the link to that article on AA and EPA/DHA, it is very informative. I have known for years that omega-3 acids were beneficial for my emotional state. As mentioned, I do not have cognitive symptoms, but have a lot of emotional symptoms. In fact, I use to have a high anxiety level and unstable emotions, even out of POIS, and that would skyrocket in POIS. So, even before developing my pre-pack, I was using omega-3 to reduce anxiety, mood swings, irritability, and all of my emotional symptoms. In the article you suggested, there is an interesting note about taking some gamma linolenic acid, or GLA, when you take DHA. I was glad to see that hemp, which I add to my smoothies and cereals in the form of hemp heart, and spirulina, that I take on its own ( it ruins the taste of my smoothies!), are good sources of GLA.
LOL, about the 2010 study on cortisol, in order to lower cortisol and stress, I will have to hang out more with my tennis buddies and stay away from my spouse.... ;) Unless I compensate with meditation, yoga and tai chi, like I have been doing :)
I totally agree with you, that inhibitors are more effective if taken before the triggering event occurs. It was the premise of my pre-pack strategy, and leads to good results for me. Inhibitors acting downstream ( cox, lox, cyp450), as you noticed, can still show high efficiency if taken after release but before the symptoms appears. In that since NSAIDS like celecoxib blocking COX2 , and a good 5-LOX inhibitor like boswellia could be a good "last minute combo" after release, before symptoms appear.
About AA, it seems that the presence of lipid peroxidation products seriously aggravate the negative effects of AA ( https://en.wikipedia.org/wiki/Arachidonic_acid#Dietary_arachidonic_acid_and_inflammation ). This could be another good reason for the various antioxidants of my pre-pack to help lower my POIS symptoms severity. For example, my "friend" curcumin is good at inhibiting lipid peroxidation ( https://www.researchgate.net/publication/15483898_Curcuminoids_as_Potent_Inhibitors_of_Lipid_Peroxidation ), as well as the EGCG found in my green tea extract ( https://www.ncbi.nlm.nih.gov/pubmed/20852116 ). And I suppose that my other antioxidants sources, like rosemary essential oil, must have that property, too. All together, they do a good teamwork, though.
I would like to add, for the benefit of all members, that it is never too late to take substances and products that helps reducing inflammation and the POIS inflammatory cascade. Granted, they are more efficient when taken before, but taking them late will be better than not taking them.
I wish you good luck for your research fellowship application, Nanni. I look forward to continue this enriching discussion with yourself and the other members.
In the meantime, I may do some tests and add some vitamin B1 to my pre-pack or on a "as needed" basis. Your explanation about B1 being a downregulator of the h1H receptors through PKC inhibition was very interesting, and seems to make it a good addition to my overall approach. In addition, it helps reduce histamine levels, which is good in my case, and in POIS cases in general, I think. I have tolerance issues with methylfolate, but not with methylcobalamine, neither with thiamine, so it's not complicated for me to add some B1.
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From month to month, I oscillate between adding supplements to my stacks and simplify them. I am in the adding mode right now, and probably will go into a subtraction mode in 3 months. lol
Lol, romies....hehe.... In my initial phase, I have done a huge number of tests. After that, I just stayed there, didn't move, keep the course, everything seems ok.... like " i had enough up and downs and side effects, I want to keep it simple and calm".
Like I wrote, I may add a little vitamine B1, because I already know I tolerate it well.
But I still have new ingredients/products I didn't try, even if I ordered them and have them here... like NADH, and Cat's claw..... at some points, I was satisfied with my pre-pack, and didn't want to risk a bad reaction to an unknown product, like I had with methylfolate, even at low dose. Anyway, I take at max 1/4 of the usual dose, for years, when trying something new, as a tolerance test, and then I raise the dose sloooooowly :)
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Hi All,
I had been looking for a more economical methyl donor than alpha-GPC. So I recently purchased a tub of betaine (TMG) and tried it out for a few days. It seems to work well. I am still symptom free replacing alpha-GPC with TMG, and TMG is dirt cheap.
So I updated the original (1st) post to use daily TMG supplementation:
tri-methylglycine, betaine (1.5g) [methyl group donor](https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_5_a_it?ie=UTF8&qid=1501608656&sr=8-5&keywords=betaine&th=1)
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Hi All,
I had been looking for a more economical methyl donor than alpha-GPC. So I recently purchased a tub of betaine (TMG) and tried it out for a few days. It seems to work well. I am still symptom free replacing alpha-GPC with TMG, and TMG is dirt cheap.
So I updated the original (1st) post to use daily TMG supplementation:
tri-methylglycine, betaine (1.5g) [methyl group donor](https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_5_a_it?ie=UTF8&qid=1501608656&sr=8-5&keywords=betaine&th=1)
That's interesting. I've been taking TMG daily for years, and yet I still feel the difference when I take alpha-GPC or CDP-Choline.
My daily AM pack has one methyl guard capsule in it, and each capsule has
Vitamin B6 (as Pyridoxal 5'-Phosphate) 6.6 mg.
Folate (as L-5-Methyltetrahydrofolate from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt) 0.4 mg.
Vitamin B12 (as Methylcobalamin) 0.4 mg.
Betaine Anhydrous (Trimethylglycine) 0.6 g.
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nanna1,
What is your C667T and A1298C status?
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Hi Romies,
I agree that alpha-GPC and CDP are higher quality sources than TMG because they both supply phosphorus at the right location and can be used to make phosphatidylcholine. I am just trying to conserve money and pure phosphatidylcholine does not seem to absorb so well from the gut. But in general, I think alpha-GPC is the best source.
I haven't done genetic testing, so I don't officially know the status of my MTHFR genes. However, in the Homocysteine Cycle, the betaine path (of homocysteine to methionine) bypasses the MTHFR (and B12) dependent folate cycle. I think that as long as I'm supplementing with SAM-e and a methyl donor (choline or betaine), the C667T and A1298C status shouldn't matter [1]. I could be wrong though.
(http://i.imgur.com/CIxD3kD.jpg)
1. Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets. (2016)
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I haven't done genetic testing, so I don't officially know the status of my MTHFR genes. However, in the Homocysteine Cycle, the betaine path (of homocysteine to methionine) bypasses the MTHFR (and B12) dependent folate cycle. I think that as long as I'm supplementing with SAM-e and a methyl donor (choline or betaine), the C667T and A1298C status shouldn't matter [1]. I could be wrong though.
1. Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets. (2016)
I agree with you that Betaine is an effective methyl donor, and it generates 1 SAMe and 2 methyl-folate molecule when it gets converted into glycine.
However, depending on your A1298C status, you might have excess SAMe in circulation from supplementation. Normally SAMe is an allosteric inhibitor of MTHFR., However, people with A1298C mutation reportedly don't have this negative feedback, as discussed in the first paper on A1298C
http://dx.doi.org/10.1006/mgme.1998.2714
Too high the serum SAMe can cause manic episodes for some people. But it may or may not be a risk for you.
I am personally A1298C homozygous, so I have been careful with SAMe, and I use a low-dose methylfolate supplement every day.
The cancer risk for methylfolate really kicks in when one takes *prolonged* doses 250% above RDA. The RDA is about 400 mcg/day. Folate deficiency and excess are both associated with colorectal cancer risk, and there are many journal pubs on this, a relative good review can be found: https://examine.com/supplements/folic-acid/
Moreever, depending on your C677T and A1298C status, your optimal folate intake level may be higher. That is why I asked you earlier.
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I agree that alpha-GPC and CDP are higher quality sources than TMG because they both supply phosphorus at the right location and can be used to make phosphatidylcholine. I am just trying to conserve money and pure phosphatidylcholine does not seem to absorb so well from the gut. But in general, I think alpha-GPC is the best source.
Sorry to hear that Cholines are a lot more expensive than TMG in your country. I had no idea, since they are priced similarly in my country.
alpha-GPC and CDP are similar in raising brain levels of choline, but
? GPC is 40% choline by weight, while CDP is 18-19% ? a pretty major difference
? CDP is essentially a uridine supplement as well as a choline supplement
? CDP has been shown to restore dopamine receptor densities in aged rodents
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908237/
? CDP was shown to improve symptoms of Parkinson?s, presumably through increasing dopamine receptor density
https://www.ncbi.nlm.nih.gov/pubmed/1863939
? Alpha-GPC has been studied and shown to enhance GH release.
https://www.ncbi.nlm.nih.gov/pubmed/22673596
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Thanks Romies for sharing that information on the MTHFR variants. I was not aware of the complexity with the variants. I knew that some were more efficient than others. But this discussion makes me curious about my gene variants. I still have a bottle of Metafolin that I have had for almost a year. As you can tell I don't take it very often anymore. It would be nice to know what my optimum dosage should be. How do you get the genetic test done? Do you go to a doctor?
I guess I lucked out with SAM-e. I have not had any negative side effects, except for one time when I took it close to bed time. That night I had poor sleep and woke up with a headache that lasted five or six hours. But I learned my lesson. :D
I agree alpha-GPC and CDP have a diverse array of benefits. I didn't know that a-GPC enhanced GH, but that makes sense since it increases acetylcholine. I may start back sup with a-GPC before my workouts! That effect of a-GPC on dopamine receptors is great for my mood. I thought about pairing my betaine dosage with equal-molar uridine monophosphate to try and mimic the cognitive effects CDP. Don't know if that will work since betaine is not apart of the CDP-choline cycle, but it may be worth a try. Thanks Romies
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Thanks Romies for sharing that information on the MTHFR variants. I was not aware of the complexity with the variants. I knew that some were more efficient than others. But this discussion makes me curious about my gene variants. I still have a bottle of Metafolin that I have had for almost a year. As you can tell I don't take it very often anymore. It would be nice to know what my optimum dosage should be. How do you get the genetic test done? Do you go to a doctor?
I did my test with 23andme.com . I did not go through my doctor, because most of the primary physicians in my town are not well versed in genetic counselling
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Thanks, romies!
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Regarding the genetic testing, I get the raw data from 23andme after testing, and then use http://geneticgenie.org/ (free) and https://promethease.com ($5) to run analysis. The MTHFR variants are mostly covered by geneticgene.
Edit: Corrected typos in the url. Hat tip nanna1.
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Thanks Romies for the gene testing info! Did you mean to write http://geneticgenie.org/ (http://geneticgenie.org/)? I'll definitely check it out.
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Thanks Romies for the gene testing info! Did you mean to write http://geneticgenie.org/ (http://geneticgenie.org/)? I'll definitely check it out.
Yes, indeed. Thanks for pointing out the typo. Some of the interpretation from geneticgenie is outdated/inaccurate. But it does distill some of the most well-understood SNP variations in one convenient table. I would also consult snpedia.com for more up-to-date information for those SNPs variants of interest.
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I have one warning about directly inhibiting mast cells. Mast cell activation is a natural part of orgasm (even for non-POIS people) and is required for ejaculation. Attenuation will necessarily lead to reduced ejaculate volume. I experienced this personally with curcumin, luteolin and niacinamide. The reason I stopped trying to directly inhibit mast cells is that I plan to impregnate my future wife and I want as much ejaculate as possible. My person preference of course, has nothing to do with the POIS disease or the pleasure of orgasm. With that said, I do not wish to discourage you or any others, who may have different goals than my own, from using mast cell inhibitors.
Hi Nanna,
your recently linked to an article about diphenyhramine/Benadryl safety, showing that it increases risk of progressive loss of higher level cognitive function and memory ( https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667 )
Following that, knowing that some members do use diphenydramine for the relief of their POIS symptoms, I have suggested some natural alternative, that would be a combo of quercetin, bromelain, vitamin C, stinging nettle, and Moducare.
However, I remembered your post quoted above, about a possible negative impact of quercetin and other mast cells stabilizers on fertility. I made some search, and stumble upon a reference that would show that, on the contrary, mast cells stabilizers improve fertility ( see #8 of the following review article: https://www.researchgate.net/publication/232810157_Male_infertility_A_critical_review_of_pharmacologic_management ). In the male fertility study cited in this review, the group of men taking a mast cell blocker showed a higher pregnancy rate than the control group.
Tell me what you think, if you have time to check this out.
At any rate, a combination of quercetin, bromelain, vitamin C, stinging nettle, and Moducare appears way safer than diphenhydramine, in the long run, and that is what I would use instead.
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Hello
I'm an 18 year old guy. I have a POIS for about 4 years. My symptoms are flu-like symptoms, mood worsening, memory impairment, lack of motivation, smell from the mouth (it's just like me, because of the bend of the gallbladder). I tried various supplements starting from fenugreek ending with NADH. In the last 2 ~ 3 months I used the preliminary package of Quantum, he helped me a lot (great thanks to him !!!), but still some of the symptoms remained. And recently Nanna laid out his post about additives. I bought them all (of the same firm ) Only without omega-3 (not enough money-lol). They came to me in the potch on August 8, I'm testing them in her day. So the results are:
- on the first day of application I was in the state of POIS after NE, and the additives significantly increased my energy and self-confidence
- August 10, I had O. without the prior package of Quantum. Apparently it was still too early to do this. I really regretted it ... I had many of the symposia.
- Now I have some problems with using the SAM-e with B complex, which contains vitamin B-12. Similar problems I had with the use of DMG. I had frequent urination, pain in the anus, and unpleasant sensations in the groin (something like an itch in the testicles). So now I take only 1 tablet of SAM-e and my condition has improved
-Also I have a significant surge of energy and the mood has stabilized, and the mind has cleared up during the time of taking these supplements.
Nanna tell me please, do you observe a diet? (Limit sugar and gluten)?
Until all this news!
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Hi Nanna,
your recently linked to an article about diphenyhramine/Benadryl safety, showing that it increases risk of progressive loss of higher level cognitive function and memory ( https://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667 )
Following that, knowing that some members do use diphenydramine for the relief of their POIS symptoms, I have suggested some natural alternative, that would be a combo of quercetin, bromelain, vitamin C, stinging nettle, and Moducare.
However, I remembered your post quoted above, about a possible negative impact of quercetin and other mast cells stabilizers on fertility. I made some search, and stumble upon a reference that would show that, on the contrary, mast cells stabilizers improve fertility ( see #8 of the following review article: https://www.researchgate.net/publication/232810157_Male_infertility_A_critical_review_of_pharmacologic_management ). In the male fertility study cited in this review, the group of men taking a mast cell blocker showed a higher pregnancy rate than the control group.
Tell me what you think, if you have time to check this out.
At any rate, a combination of quercetin, bromelain, vitamin C, stinging nettle, and Moducare appears way safer than diphenhydramine, in the long run, and that is what I would use instead.
Hi Quantum,
A side question to your discussion - if benedryl is specifically anticholinergic, and [my assumption] that is what reduces pois symptoms, is it possible that the long term risk of dementia is decreased as the people benefiting from benedryl are likely high in choline already [also my assumption - based on seeing runny nose symptoms for too much choline]; or, alternately: any substitute would need to have the same anticholinergic effects and would yield the same long term risk of dementia?
I premise this on the assumption that the anticholinergic reactions are what drive use for pois as well as long term risk of dementia, which may be off base.
Thanks!
TT
[edited for clarity]
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I was intrigued with nanna1 post and managed to get Diphenhydramine last week. I used it 2 times each time before going to sleep. Both times I had dementia during 45min to one hour before falling asleep. My mind was rushing and I had nightmare visions. I decided to stop using it.
What I fail to understand is why using anticholinergic like benadryl and in the same time trying to increase choline level?
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Wow, this is an interesting discussion about diphenhydramine, histamine and the brain. I will try my best to contribute to the discussion.
Benadryl (diphenhydramine) is marketed as a 1st generation h1-Histamine (h1H) receptor blocker (anti-histamine) [1]. The anti-allergy and sleep inducing effects come from the antihistamine effect on the h1H receptor. In the initial post of this thread there is a plausible explanation for how the h1H receptor could regulate POIS symptoms via the arachidonic acid (AA) cascade [2].
As a preface, it is important to state that acetylcholine has an anti-inflammatory effect on the brain [3]. Furthermore, acetylcholine increases nerve growth factor (NGF) and brain-derived nerve factor (BDNF) [4] associated with dendrite sprouting and neurogenesis.
In addition to blocking h1H, Benedryl also blocks the (muscarinic) acetyl-choline receptor as well [1, 5]. This anticholinergic property of diphenhydramine is a negative side effect of this medication, and its ability to cross the blood brain-barrier means that it can induce the death of cholinergic neurons and atrophy of the dendrites that connect neurons together in the brain [3, 4].
Most 2nd generation antihistamines cannot cross the blood-brain barrier, do not block h1H receptor in the brain and as a result, do not cause drowsiness [5]. My guess as to why diphenhydramine is used by some in the POIS community is that it blocks the h1H receptor in the brain and reduces histamine-related brain inflammation. However, one has to weigh this against the anticholinergic-dependent short-term and long-term memory loss associated with diphenhydramine. The basic question is: Is it worth it?
I would agree with Quantum that the supplements like quercetin, bromelain, vitamin C, stinging nettle, and Moducare have clear advantages relative to diphenhydramine, but they have different mechanisms. Not only that, but they seem generally healthy even if you do not have POIS. Vitamin C is one of the most abundant vitamins in semen fluid [6] and everything I have read about Maritime Pine bark extract is positive for the reproductive system [7]. Both quercetin and bromelain have health benefits a mile long when consumed properly at sufficient doses (search on https://scholar.google.com/).
ThisType and POISse, in relation to the questions about choline. As stated above, acetylcholine is anti-inflammatory [3]. Moreover, choline (phosphorylcholine) is needed to produce semen fluid [6]. According to the POIS Cascade hypothesis (https://poiscenter.com/forums/index.php?topic=2502.0), the reason AA is released from the phospholipid bilayer (cell wall) is that the body is trying to recruit more choline from the back-up reserves (phosphatidylcholine) in the cell wall. In other words, the body thinks that there is not enough free-choline to make/replace neurotransmitters and semen. The AA release and resulting systemic inflammation is just a byproduct.
1. https://en.wikipedia.org/wiki/Diphenhydramine (https://en.wikipedia.org/wiki/Diphenhydramine)
2. POIS cure: theory & supplement stack (https://poiscenter.com/forums/index.php?topic=2502.0)
3. Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model (http://www.sciencedirect.com/science/article/pii/S096999611100283X)
4. Positive Feedback between Acetylcholine and the Neurotrophins Nerve Growth Factor and Brain-derived Neurotrophic Factor in the Rat Hippocampus (http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.1994.tb00312.x/abstract)
5. https://en.wikipedia.org/wiki/H1_antagonist#Second-generation_and_third-generation_.28selective.2C_non-sedating.29
6. https://en.wikipedia.org/wiki/Semen#Human_semen
7. https://poiscenter.com/forums/index.php?topic=2505.msg21603#msg21603 (https://poiscenter.com/forums/index.php?topic=2505.msg21603#msg21603)
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Hi Quantum,
A side question to your discussion - if benedryl is specifically anticholinergic, and [my assumption] that is what reduces pois symptoms, is it possible that the long term risk of dementia is decreased as the people benefiting from benedryl are likely high in choline already [also my assumption - based on seeing runny nose symptoms for too much choline]; or, alternately: any substitute would need to have the same anticholinergic effects and would yield the same long term risk of dementia?
I premise this on the assumption that the anticholinergic reactions are what drive use for pois as well as long term risk of dementia, which may be off base.
Thanks!
TT
[edited for clarity]
Hi TT,
there is not much we know for sure, about POIS, but I do not feel that it is the anticholinergic properties of Benadryl that are useful in POIS, I think it is rather its antihistaminic properties. I have 2 reasons to support this hypothesis.
First, POIS seems to me, and to many, to include an inflammation problem. Histamine release is often associated with inflammatory conditions ( like through mast cells degranulation). The strong antihistaminic properties of diphenhydramine should then be what is very useful in blocking POIS symptoms. In this interpretation, the anticholinergic effects come as side effects, and in POIS, I think they are not welcomed. But on the short term, it seems that the benefits of the antihistamine effects overshadows the disadvantage of the anticholinergic side effects. As with many medication, it is a give and take situation.
My second reason is POIS is that POIS is associated with cognitive problems like memory problem, loss of problem solving capacities, speech problems, etc..... Cognitive problems is clearly associated, in medicine, with a deficit in cholinergic activity, and they are worsen by anticholinergic drugs. On the opposite, cholinergic drugs are used in dementia. For POIS, many members have reported good results with cholinergic supplements, like lecithin, eggs, TMG, and also with the cholinergic drug Mytelase.
So, I am not sure about a POIS type with too much cholinergic activity ( runny nose can alos come from a high histaminergic activity, like in allergic rhinitis). But that is just my opinion, and we do not have those kind of answers yet, and reality is often much more complex than the unbalance of just one neurotransmitter activity ( even the serotonin hypothesis of depression is challenged, and some researchers talk about dopaminergic depression, hence resistance to standard, serotoninergic antidepressant).
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Hi Rinat,
Thank you for your question. I will limit the discussion to the supplements you mentioned/purchased. Firstly, I do not see a reason to stop taking your prepack if it is benefitting you. I was not cured within two days. Below is a bunch of info that you may already know, but I do not want to assume.
I totally understand the economic reason for not getting the omega-3s and vitamin D3. I switched from alphaGPC to betaine&uridine for economic reasons. However, without omega-3s and D3, the stack would be missing inhibitors of AA (omega-6) access to the PLA2/COX/LOX/CPY450 enzymes. There are some PLA2/COX/LOX blockers that Quantum and others have discussed and may be more economical (link (https://poiscenter.com/forums/index.php?topic=2505.msg21554#msg21554)). Asprin is a pretty cheap COX inhibitor. Grapefruit juice and pygeum (https://en.wikipedia.org/wiki/Pygeum_(herbal_remedy)) are pretty cheap CYP450 inhibitors. SAMe and B6 do modestly block COX. In my opinion, in order for the POIS Cascade stack to be complete, the PLA2/COX/LOX/CPY450 enzymes somehow need to be addressing.
Quick question: did you mean to say you ordered Di-methylglycine (DMG) or tri-methylglycine (TMG, betaine)? Di-methylglycine may not work with this stack. The POIS Cascade stack hacks the Homocysteine Cycle and the Folate Cycle. Below is a visual of what I mean.
Purple arrows inserted by me:
(1)SAMe, (2)TMG (betaine), (3)B12, (4)B6, (5)B9 (metafolin)
(http://i.imgur.com/hq96vF1.jpg)
Choline sources like alphaGPC and PC are metabolized into TMG/betaine to supply the homocysteine cycle with one methyl group. DMG is the end-product which at high levels can slow the homocysteine cycle down. Without a good choline or betaine source, homocysteine buildup could become an issue.
You mentioned B complex. It may be important to check that the B6 dosage is not too high. I use 2mg of B6 (100% US RDA). Above 100mg a day can be toxic. If it is difficult to find a B6 supplement between 2mg-25mg there are food sources (https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) (see Table 2: Selected Food Sources of Vitamin B6).
When I first started alphaGPC, I was taking 1.2g a day. This caused lower back, hip and pelvis pain. This was mainly nerve pain around the bone. I had to back off the dose and take 300mg per day. When the pain went away, I increased it to 600mg a day for a few days and then after two more weeks increased the dose to 1.2g. I discussed a little about the slow build up to choline in the Note: (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) section. With that said, I am not sure why you are experiencing pain. If the pain persist, please see a healthcare professional.
I do limit my sugar to fruit and vegetable sources. Usually, no cakes, pies or cookies. If I am with friends, I might cheat a little on the pastry restriction. I have cut most gluten sources out of my diet. However, I still eat egg rolls (the external batter is sometimes made with wheat). I don?t consume dairy products at all (except from the egg rolls/batter ;)). I eat plenty of carbs from potatoes, beans, apples and other fruits, fruit smoothies, vegan protein shakes, etc...
I know this was a lot, I wasn`t sure if I was understanding your questions so I just threw in a bunch of information which may or may not be useful. Wish you well! :)
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Nanna,thanks for the detailed answer.
- I took earlier dimethylglycine (5 months ago). His reception caused frequent urination, pain in the anus. There is an identical pain now. But after limiting the SAM-e to 1 tablet, there is almost no pain. Why do you think this could happen?
Here's what I now accept:
- https://www.iherb.com/pr/Now-Foods-SAMe-200-mg-60-Tablets/812 (1 time per day)
- https://www.iherb.com/pr/Doctor-s-Best-Best-Vitamin-D3-2000-IU-180-Softgels/17135 (1 time per day)
- https://www.iherb.com/pr/Life-Extension-Mega-Benfotiamine-250-mg-120-Veggie-Caps/13192 (1 time per day)
- https://www.iherb.com/pr/Now-Foods-Alpha-GPC-300-mg-60-Vcaps/12803 (2 times a day)
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Hi Rinat, :)
Sorry for the late reply. I am not sure why you experienced those specific pains, since I did not have the same experience. But I am glad you have managed with a reduced dose. I also take one SAM-e (200mg/day) and sometimes a second [SAM-e (200mg) & TMG 1g] shortly after an orgasm as a safety precaution.
Best wishes!
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Hi Quantum,
Thanks for sharing the review article on male fertility management. It had a lot of good sections. I particularly like the [zinc] (5.7) and the [astaxanthin and lycopene] (5.9) section and am supplementing with these again. In relation to your suggestion on mast cell stabilizers:
However, I remembered your post quoted above, about a possible negative impact of quercetin and other mast cells stabilizers on fertility. I made some search, and stumble upon a reference that would show that, on the contrary, mast cells stabilizers improve fertility ( see #8 of the following review article: https://www.researchgate.net/publication/232810157_Male_infertility_A_critical_review_of_pharmacologic_management ). In the male fertility study cited in this review, the group of men taking a mast cell blocker showed a higher pregnancy rate than the control group.
Tell me what you think, if you have time to check this out.
I do believe reducing inflammation will improve sperm quality, however the mast cell stabilizer they use (Ketotifen) is a synthetic h1H blocker with very narrow properties. I did a little digging through the literature on mast cell regulation. I am not certain those positive Ketotifen results on sperm quality can be extended to herbal mast cell stabilizers.
Flavonoids (i.e. curcumin, luteolin, quercetin, etc?) bind to and act on the estrogen (ER) and progesterone receptors (PR) [1, 2]. The positive effects of these flavonoids on the brain are due mostly to their estrogenic [1] and progestogenic signaling [3, 4]. Progesterone stabilizes mast cells, while estrogen causes mast cell activation [5, 6]. Flavonoids stabilize mast cells by enhancing progesterone signaling (see Figure 3 (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3)) [2]. Diosgenin, from Fenugreek and Wild Yam extracts, is a prodrug for progesterone [7] and Quercetin can increase the secretion of progesterone [8]. Additionally, flavonoids reduce inflammation through progesterone signaling where progesterone inactivates the Phospholipase A2 enzyme required for the arachidonic acid (AA) cascade [9, 10].
(http://i.imgur.com/eEHfswS.png)
Essential Reproduction. Martin H. Johnson, Barry J. Everitt. (1988)
The anti-inflammatory effects of flavonoids cannot be explained by their antioxidant properties, since the universal antioxidant N-acetylcysteine does not display such anti-inflammatory effects [11]. Nonetheless, progesterone/estrogen signaling can influence the antioxidant status of the body by regulating the zinc/copper ratio [12] with estrogen favoring copper accumulation [13]. An important hormonal difference to note is that while flavonoids can stimulate the estrogen receptor directly in the absence of estrogen, flavonoids require the addition of progesterone in order to enhance PR signaling (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3).
So flavonoid supplementation is primarily a type of hormone therapy [14]. This is why I cautioned against taking flavonoid extracts in the original post (https://poiscenter.com/forums/index.php?topic=2502.0). At high concentrations, (achieved through extracts) some become estrogenic. I suspect that the deleterious effect that curcumin has on sperm (http://onlinelibrary.wiley.com/doi/10.1002/mrd.21276/full)[15] at high concentrations might be attributable to its estrogen receptor binding, but as far as I know, this idea has not been explored scientifically. However, other flavonoids like licorice are less estrogenic (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig4) and have positive effects on sperm at high (extract) concentrations[16, 17].
Flavonoid (non-competitive) binding to the progesterone receptor appears to sensitize the receptor to progesterone stimulation. From this standpoint, it would seem like one would want to take the progesterone prodrug, pregnenolone, to enhance the curcumin/quercetin/luteolin mast stabilizing, anti-inflammatory and neuroprotection effect. Both Fenugreek extract and Wild Yam extract contain some of the progesterone prodrug, diosgenin, in addition to their own set of flavonoids. I suspect that prodrugs will synergistically boost the effects of flavonoids on POIS symptoms. Also, from the list of herbs (http://www.cancersupportivecare.com/estrogenherbdata.html#table1) studied the 2nd reference, it appears that mistletoe and damiana had the largest progesterone/estrogen stimulation ratios (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3) (even higher than turmeric and ginger). I do make it a point to get flavonoids through foods (capers, onions, apples, spicy foods, vegetable currys).
Note: pregnenolone (PREG) and pregnenolone sulfate (PREGS) have different properties, but can be converted back-and-forth.
(http://i.imgur.com/4tOUktk.jpg)
Thanks again for sharing the article (https://www.researchgate.net/publication/232810157_Male_infertility_A_critical_review_of_pharmacologic_management). I enjoyed reading through it.
1. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (2013) (https://www.hindawi.com/journals/ecam/2013/127075/)
2. Estrogen and progestin bioactivity of foods, herbs, and spices. (1998) (http://www.cancersupportivecare.com/estrogenherb.html)
3. The Effects of Progesterone on Glial Cell Line-derived Neurotrophic Factor Secretion from C6 Glioma Cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586917/pdf/IJBMS-15-1046.pdf)
4. Progesterone, BDNF and Neuroprotection (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582842/)
5. Progesterone inhibits mast cell secretion. (2006) (http://journals.sagepub.com/doi/abs/10.1177/039463200601900408?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed)
6. Role of female sex hormones, estradiol and progesterone, in mast cell behavior (2012) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/)
7. https://en.wikipedia.org/wiki/Diosgenin#Clinical_uses (https://en.wikipedia.org/wiki/Diosgenin#Clinical_uses)
8. Effects of genistein, resveratrol, and quercetin on steroidogenesis and proliferation of MA-10 mouse Leydig tumor cells.
9. Essential Reproduction. Martin H. Johnson, Barry J. Everitt. (1988)
10. Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia. (2014) (https://www.ncbi.nlm.nih.gov/pubmed/25080336)
11. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. (https://www.ncbi.nlm.nih.gov/pubmed/9581680)
12. Copper toxicity, oxidative stress, and antioxidant nutrients (2003) (https://www.ncbi.nlm.nih.gov/pubmed/12821289)
13. Effect of estrogen on serum and tissue levels of copper and zinc. (https://www.ncbi.nlm.nih.gov/pubmed/2626984)
14. Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851288/)
15. Can curcumin provide an ideal contraceptive? (2011) (http://onlinelibrary.wiley.com/doi/10.1002/mrd.21276/full)
16. Effects of Licorice Extract on Sperm Motility of Chilled Stored Ram Semen (http://www.jihcoed.com/ihj/index.php/j/article/view/974)
17. Improved In Vitro Fertilization Ability of Mouse Sperm Caused by the Addition of Licorice Extract to the Preincubation Medium (https://benthamopen.com/ABSTRACT/TORSJ-6-1)
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Hi Nanna,
I am glad if you found some interesting information in the article. Astaxanthin is a great antioxidant, I use it before sport and if needed when some POIS symptoms left ( but only 4mg, not 16mg like mentioned in the review article). Lycopene is part of my POIS pre-pack.
Progesterone have been talked about a lot on the forum in the past ( see this thread, for example: http://poiscenter.com/forums/index.php?topic=16.0 ). As anything POIS related, it helped some members, and others had no effect or got worse with it, which is not surprising if there is, effectively, more than just one type of POIS. Of interest to mention is that there is one a the few POIS case reports that is related to a success in using progesterone in POIS treatment. The POIS sufferer has reported to his doctor relief of POIS during his wife's pregnancy. His doctor tried progesterone supplements at the time of release, and it worked for him.
For the benefit of other members, in particular those that have not read all of this discussion, I would like to point out that your suggestion to stay away from quercetin and other natural products that may interact with progesterone receptors is related to your project of having children, and to maximize your fertility. So, your explanations and references do not aim at proving that those natural products are not useful in controlling POIS symptoms, but that they may affect the quality of sperm and affect fertility. For someone like myself, who even had vasectomy, I benefit from quercetin, curcumin and the like, they are really useful in controlling my POIS symptoms, and of course, their potential effects on my fertility is not an issue at all. It wouldn't be an issue for any other member who are single or not currently planning to impregnate their wife.
In the fertility review article, they also refer, apart from the ketotifen study, to a study using the lesser known mast-cell stabilizer tranilast. This one is not a histamine receptors blockers. Its mechanism of action is not completely elucidated but it appears to work through the inhibition of a variety of pro-inflammatory cytokines ( see https://www.ncbi.nlm.nih.gov/pubmed/26455295 , and https://www.ncbi.nlm.nih.gov/pubmed/20398193 , for examples ). In the review article on fertility, a 28,6% fertilization rate was observed in the tranilast group, vs 0% in the control group.
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Hi Quantum,
Thanks for clarifying the context of the discussion on flavonoids and male fertility. I mainly wanted to discuss how flavonoids as plant hormones effect sperm quality and reproduction. As a personal goal, I would like to remain as fertile as possible while controlling POIS symptoms. So when choosing supplements for myself, I take into account fertility as well as relieving POIS. But these two goals are not necessarily the same and not necessarily relevant to all POISers.
In terms of POIS, any flavonoid that increases progesterone signaling should help stabilize mast cells and inhibit the arachidonic acid (AA) cascade. I did want to stress the idea that the beneficial effects of flavonoids could be enhanced by pregnenolone (PREG) supplementation since flavonoids require progesterone in the blood stream to stabilize mast cells and inhibit AA release. Moreover, some guys that have not responded positively to flavonoids in the past, may find benefits by combining flavonoid supplements with PREG. As a side note, I think taking hormone prodrugs like PREG may be safer than taking the active hormone progesterone, since the body can shut down the conversion when the active hormone gets too high. PREG also converts to DHEA which is anti-inflammatory as well. But I am glad that some have found relief from taking progesterone.
P.S. Thanks for pointing out the tranilast study. I must have overlooked it.
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I totally understand the economic reason for not getting the omega-3s and vitamin D3. I switched from alphaGPC to betaine&uridine for economic reasons. However, without omega-3s and D3, the stack would be missing inhibitors of AA (omega-6) access to the PLA2/COX/LOX/CPY450 enzymes. There are some PLA2/COX/LOX blockers that Quantum and others have discussed and may be more economical (link (https://poiscenter.com/forums/index.php?topic=2505.msg21554#msg21554)). Asprin is a pretty cheap COX inhibitor. Grapefruit juice and pygeum (https://en.wikipedia.org/wiki/Pygeum_(herbal_remedy)) are pretty cheap CYP450 inhibitors. SAMe and B6 do modestly block COX. In my opinion, in order for the POIS Cascade stack to be complete, the PLA2/COX/LOX/CPY450 enzymes somehow need to be addressing.
Nanna1, I like the scientific discussion here. However, I have to point out several MAJOR RISKs associated with Aspirin, Grapefruit juice(CYP3A4 inhibitor).
Aspirin can be a mast-cell activator for some people (more common than POIS to the best of my knowledge), and can significant worsen POIS symptom. A well known example is Aspirin-induced asthma.
https://en.wikipedia.org/wiki/Aspirin-induced_asthma
https://link.springer.com/article/10.2165/00003495-200464210-00004
CYP450 inhibitors is a major source of drug interactions, and I think most people should stay away from it if possible. Grapefruit juice is a potent CYP3A4 inhibitor, which is known to cause accidental overdose in statins, several SSRI, many analgesics, azole antifungals, TCAs. Many readers of this forum take other OTC or prescription meds, and should be very careful.
Even though CYP1A1, CYP1A2, CYP1B1 can convert AA into HETEs and EETs. Many HETEs dampens allergic responses, or even increase progesterone production ( https://en.wikipedia.org/wiki/5-Hydroxyeicosatetraenoic_acid )
Given that so many prescription and OTC medicines rely on CYP450 to metabolize, I think it is prudent NOT to tinker with CYP450 activity for most people.
In fact, I take quercetin only in my prepack, as oppose to a daily dose, because it is a CYP1A2, CYP2C8, CYP3A4 inhibitor.
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Choline sources like alphaGPC and PC are metabolized into TMG/betaine to supply the homocysteine cycle with one methyl group. DMG is the end-product which at high levels can slow the homocysteine cycle down. Without a good choline or betaine source, homocysteine buildup could become an issue.
DMG is not the end-product of TMG metabolism. Glycine is. Unless someone has dimethylglycine dehydrogenase (DMGDH) deficiency from a genetic defect in ones mitochondria gene, DMG can be further converted into sarcosine, and then to glycine. This process also generates two additional unit of methyl-folate, if one is not folate deficient.
See fig.1 of https://www.ncbi.nlm.nih.gov/pubmed/11231903
http://www.pnas.org/content/101/12/4234/F1.expansion.html
https://en.wikipedia.org/wiki/Sarcosine_dehydrogenase
I do agree with you that TMG is much more effective than DMG. But I don't think DMG leads to high HCY levels. Folate deficiency or MTHR issues lead to high HCY levels
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When I first started alphaGPC, I was taking 1.2g a day. This caused lower back, hip and pelvis pain. This was mainly nerve pain around the bone. I had to back off the dose and take 300mg per day. When the pain went away, I increased it to 600mg a day for a few days and then after two more weeks increased the dose to 1.2g. I discussed a little about the slow build up to choline in the Note: (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) section. With that said, I am not sure why you are experiencing pain. If the pain persist, please see a healthcare professional.
I suspect that in your case the high-dose choline supplementation led to excess acetylcholine in peripheral nervous system, which can cause strong muscle contraction and muscle pain. Most common excess acetylcholine pain occurs in low back and shoulders.
Excess acetylcholine pain can be resolved in 1-2 hrs with a low-dose piracetame. Be careful here, because too much piracetame can cause low acetylcholine, which gives a different kind of headache, similar to migraine. This migraine can be relieved by a small dose of choline supplementation.
The bigger problem with excess acetylcholine is depression, anxiety and brain fog. There are many anecdote reports about this:
http://www.longecity.org/forum/topic/64320-excessive-acetylcholine-makes-you-dumb/
http://www.longecity.org/forum/topic/81386-choline-induced-depression-brain-fog-help/
My personal experience is that Citi-Choline can cause the most mood change. I had several incidences where 500mg of Citi-choline put me into a deep depressed mood within 2 hrs of taking it. It felt like a deluge of negative thoughts that simply cannot be turned off. The effect lasted for 6-8 hrs. This was before I know about piracetame, which could reduce acetylcholine and resolve the mood issue.
Interestingly, I never had similar issues with Alpha-GPC, eggs, lecithin.
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Hello, Nanna
So I thought I might try your method but I have a few questions about your usage :
1- So you say that you take the first part on an empty stomach "twice", what do you mean by that ? do I need to like, take it twice before breakfast or do I actually have to fast the entire day ?
2- You mentioned that you take 2mg of VitB6, what do you mean by that ? You meant 2g of B6 or you actually did mean 2mg of B6 ?
3- Lastly, any update on your personal pack ? any stuff that might have side effects that I need to be aware of ? any change in the pack at all ?
Thanks
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Hi Nas,
Thank you for your questions.
- I do not fast when taking this stack. When I first wake up in the morning, I take the water-solubles with about 3/4 cup of water or juice. The amount water is not as important as just washing down all the supplements. Then I take the water-solubles once more usually between lunch and dinner. I am very lazy with my second dose and many times forget to take it (since I am usually at work during this time frame). But on orgasm days, I cannot forget to take it! Even if it is late and close to bedtime, if I have an orgasm, I have to take the second dose. The fat-solubles are taken first with breakfast and then either lunch or dinner.
- I actually meant 2mg of B6 (see Mayo Clinic: Vitamin B6 Safety (http://www.mayoclinic.org/drugs-supplements/vitamin-b6/safety/hrb-20058788)). I know that is a really small amount. According to the National Institutes of Health, the upper B6 limit is 100mg per day (https://ods.od.nih.gov/pdf/factsheets/VitaminB6-Consumer.pdf). I break open B6 pills and take fractional amounts, but I do not recommend this for someone first trying out this stack. If you just want to get started, this is a good source of B6 (Solgar - Vitamin B6 25 mg Tablets 100 Count (https://www.amazon.com/s/ref=nb_sb_noss_1?url=search-alias%3Daps&field-keywords=b6+25mg&rh=i%3Aaps%2Ck%3Ab6+25mg)) or a combo pack like (NOW SAMe 200 mg,60 Tablets (https://www.amazon.com/NOW-SAMe-200-60-Tablets/dp/B0013OW3V6/ref=sr_1_5_a_it?ie=UTF8&qid=1504369367&sr=8-5&keywords=same+200mg)). I eat a lot of B6 rich foods, so I do not know exactly what my total daily intake is. I just know that I am not deficient.
- In terms of updates:
- I no longer think betaine is a viable substitute for a good choline source. Betaine does help improve the way I feel and energy, but I can tell the difference with alpha-GPC and Lecithin.
- I cut red-meat (pork and beef) out of my diet since those are major sources of omega-6 (LA and arachidonic acid).
- I started taking zinc (22mg) and carotenoids (lutein, zeaxanthin, lycopene, astaxanthin) daily for sperm quality benefits and general health (not for POIS reasons).
There are no new side effects to report. Just remember, I had to slowly increase the dose of alpha-GPC (choline) over the course of about a week to prevent choline related lower-back ache. I described this in the "Note" section. However, if you choose to use betaine (TMG) as the methyl donor, to the best of my knowledge, betaine dosen't have these side effects.
The water soluble supplements can have an effect quite quickly, but the fat-soluble supplements could take some time. Give it about a month before expecting to see full benefits if any. I hope this was helpful. Let me know if you have anymore questions.
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Hi nanna1,
I want to chime in on this discussion on the relation among quercetin, curcumin, mast cell activation, progesterone and estrogen, because I personally take quercetin and curcumin often, and I invest a lot of time to minimize drug/supplement interaction.
You raised several interesting points and I enjoyed reading your references.
My main points are
1. The biggest reason to use Quercetin and Curcumin is their TDO/IDO inhibitor properties. Mast cell stabilizer is a nice BUT secondary effect.
2. Dietary supplement of Quercetin are associated with serum level far below the concentration needed to be highly estrogenic.
3. The main factors in fertility are sperm count and sperm motility. I have yet to see research papers that show significant effects from quercetin or curcumin at concentrations similar to dietary supplement levels.
Flavonoids (i.e. curcumin, luteolin, quercetin, etc?) bind to and act on the estrogen (ER) and progesterone receptors (PR) [1, 2].
I am not sure about how strong an estrogenic effect curcumin and quercetin actually have. In Fig.3 of Ref.1, you can see that estrogen induction effects becomes significant only when quercetin concentration exceeds 4uM. If you use Quantum's dosage (500mg), the peak serum concentration is only about 1uM (interpolating from the data found here (https://examine.com/supplements/quercetin/#summary3-1)). Also considering the half-life of quercetin is 11hrs (https://www.ncbi.nlm.nih.gov/pubmed/11361045), the active concentration is even smaller than 1uM, since the paper measured the effect by incubating the cell line in a constant-concentration quercetin solution for 20hrs. Eyeballing Fig.3, you can roughly estimate the effect is less than 2% of 1nM of estradiol for 20hrs. Assuming the effect of estradiol scales linearly with its concentration, quercetin will induce an effect less than 20pM of estradiol, in comparison to the reference range for average male adult (50-200pM (https://en.wikipedia.org/wiki/Estradiol)).
To set the right context, skin contact with thermal paper (receipts etc) for 4mins gives you a dose of BPA (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206219/) (via skin absoprtion) approximately 2x more potent than a 500mg quercetin dose.
I will be interested in reading other paper you may have on curcumin.
The positive effects of these flavonoids on the brain are due mostly to their estrogenic [1] and progestogenic signaling [3, 4].
No, the main effects of quercetin and curcumin for POIS treatment is their TDO/IDO inhibition. please see quantum's original post on his prepack for details.
Progesterone stabilizes mast cells, while estrogen causes mast cell activation [5, 6]. Flavonoids stabilize mast cells by enhancing progesterone signaling (see Figure 3 (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3)) [2]. Diosgenin, from Fenugreek and Wild Yam extracts, is a prodrug for progesterone [7] and Quercetin can increase the secretion of progesterone [8]. Additionally, flavonoids reduce inflammation through progesterone signaling where progesterone inactivates the Phospholipase A2 enzyme required for the arachidonic acid (AA) cascade [9, 10].
The anti-inflammatory effects of flavonoids cannot be explained by their antioxidant properties, since the universal antioxidant N-acetylcysteine does not display such anti-inflammatory effects [11]. Nonetheless, progesterone/estrogen signaling can influence the antioxidant status of the body by regulating the zinc/copper ratio [12] with estrogen favoring copper accumulation [13]. An important hormonal difference to note is that while flavonoids can stimulate the estrogen receptor directly in the absence of estrogen, flavonoids require the addition of progesterone in order to enhance PR signaling (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3).
So flavonoid supplementation is primarily a type of hormone therapy [14]. This is why I cautioned against taking flavonoid extracts in the original post (https://poiscenter.com/forums/index.php?topic=2502.0). At high concentrations, (achieved through extracts) some become estrogenic.
No. Some flavonoid, such as soy-derived isoflavonoid and Diosgenin, have strong hormonal effects. But that does not mean quercetin and curcumin are equally estrogenic.
The effect of quercetin on progesterone is controversial. There are also papers (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693932/) showing quercetin inhibits progesterone production.
I suspect that the deleterious effect that curcumin has on sperm (http://onlinelibrary.wiley.com/doi/10.1002/mrd.21276/full)[15] at high concentrations might be attributable to its estrogen receptor binding, but as far as I know, this idea has not been explored scientifically.
The paper by Naz is not about oral intake of curcumin, but rather directly applying curcumin solution to a vagina!! The concentration he used is really high, from 31.25uM to 500uM. According to another study, 31uM of curcumin starts to be toxic to red blood cells (forming spiky protrusions on red blood cells) (https://www.ncbi.nlm.nih.gov/pubmed/24023289). One would need to worry about anemia before sperm motility! Also, there is no evidence that semen has particularly high concentration of curcumin than blood either.
If curcumin is a significant issue, Indians would have trouble producing babies, because their diets are very high in turmeric. But it looks like they will be the most populated country before 2030!
However, other flavonoids like licorice are less estrogenic (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig4) and have positive effects on sperm at high (extract) concentrations[16, 17].
Flavonoid (non-competitive) binding to the progesterone receptor appears to sensitize the receptor to progesterone stimulation. From this standpoint, it would seem like one would want to take the progesterone prodrug, pregnenolone, to enhance the curcumin/quercetin/luteolin mast stabilizing, anti-inflammatory and neuroprotection effect. Both Fenugreek extract and Wild Yam extract contain some of the progesterone prodrug, diosgenin, in addition to their own set of flavonoids. I suspect that prodrugs will synergistically boost the effects of flavonoids on POIS symptoms. Also, from the list of herbs (http://www.cancersupportivecare.com/estrogenherbdata.html#table1) studied the 2nd reference, it appears that mistletoe and damiana had the largest progesterone/estrogen stimulation ratios (http://www.cancersupportivecare.com/estrogenherbdata.html#herbfig3) (even higher than turmeric and ginger). I do make it a point to get flavonoids through foods (capers, onions, apples, spicy foods, vegetable currys).
1. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (2013) (https://www.hindawi.com/journals/ecam/2013/127075/)
It is far more tricky to supplement progesterone and pregnenolone than quercetin/curcumin. One should always get carefully tested on their hormone levels, and consult an endocrinologist. Without knowing the status of Hypothalamic?pituitary?gonadal axis and Hypothalamic?pituitary?adrenal axis, it is very hard to predict the result of supplementing progesterone, unless you know how different pathways in your body is upregulated or downregulated. I know two people from the gym who developed hypogonadism from taking progesterone, including fertility issues, enlarged breasts, etc, the very problem you want to avoid.
(https://i.imgur.com/okn26O4.png)
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Hello everyone!
-I want to share my results. For about a month, I've been testing Nann's supplements, but I'm testing omega-3 at 2 grams for about 10 days. A week ago I had an orgasm, the condition was good, but I still felt some flu-like symptoms for about 24 hours, then everything went away (I think it happened, because I used very little time for omega-3).
-I have acne their amount decreased. I think it's because of the decrease in inflammation.
-Nanna 1.5 grams of trimethyl glycine per day is it enough or do you recommend 3g? Just from a large amount of TMG, I seem to have a strong dry mouth
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Hi Rinat,
I am glad you are seeing relief of some symptoms. On none orgasm days I typically just take a single betaine (TMG) 1.5g dose. It's hard to get the second dose in if I am at work. However, on O days, I am taking an extra TMG (and other water solubles) dose after the orgasm to speed up the removal of histamine and norepinephrine from my body. Methyl donors lower histamine and norepinephrine levels through the homocysteine cycle (http://i.imgur.com/hq96vF1.jpg) [1, 2].
TMG and alpha-GPC are natural osmolytes (https://en.wikipedia.org/wiki/Osmolyte) which control the flow of water into an out of cells (think osmosis, similar to electrolytes). When cells are dry (lacking enough water) osmolytes carry water into the cell, and when cells are swelling (too much water) osmolytes carry water out of the cell. I drink about roughly 4 bottles of 16.9FL OZ. of water a day (usually between meals). This is a total of 67.6 FL OZ. per day. The Mayo Clinic recommends much more water per day (http://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/water/art-20044256), but their recommendation pertains to total fluids (including sources like fruits and veggies). If someone is experiencing dry mouth from TMG or alpha-GPC, it could be that TMG/alpha-GPC is sucking water out of the blood stream and into the cells to bring the cell`s water content up to normal levels, leaving less water for saliva production (similar to electrolytes or salt). In this case, drinking more water can help.
I hope this was helpful. :)
1. Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers. (https://www.ncbi.nlm.nih.gov/pubmed/3961029)
2. https://en.wikipedia.org/wiki/Histamine_N-methyltransferase (https://en.wikipedia.org/wiki/Histamine_N-methyltransferase)
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Hi Nanna!
Thanky so much for your advices!! I will try to drink more water!(But when I used Alpha GPH I did not experience a feeling of dryness)
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Also Rinat, I forgot to say that I try to reduce dietary consumption of the omega-6, arachidonic acid (AA), by reducing certain fatty meets in my diet (Contribution of meat fat to dietary arachidonic acid. (https://www.ncbi.nlm.nih.gov/pubmed/9590632)). I think reducing dietary AA helps a lot when taking the omega-3s, but you may already be doing this.
Thanks for posting your results.
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After over a decade, I believe I have cured my POIS. I wanted to open source my supplement stack to get feedback/improvemnets and to help others going through what I went through.
During orgasm there is a transient increase in norepinephrine release [1]. Postorgasmic illness syndrome (POIS) occurs when there is an overexpression of the α1-adrenergic (a1A) receptor and a subsequent over-stimulation of a1A by rising norepinephrine levels [2]. The purpose of this α1-adrenergic, a1A, stimulation is to obtain methyl groups (choline) from the phospholipid bilayer stored in the form of phosphatidylcholine (PC) [3]. a1A stimulation upregulates the enzyme Phospholipase A2, which removes a PC-arachidonic acid molecule from the bilayer and cleaves the bond holding PC to arachidonic acid (omega-6 fatty acid, AA) [4]. PC is now free to produce choline and replenish the pool of methyl groups consumed in both semen and neurotransmitter production.
However, the release of arachidonic acid, or AA, is problematic since it is a key substrate for the production of inflammatory hormones by the enzymes LOX-(5, 9), COX-(1, 2) and the CYP450 group [4]. It is the rapid release of AA and mass production of inflammatory hormones (eicosanoids such as prostaglandin G2) that causes sickness associated with POIS.
Also, there is a parallel cause of POIS, replacing norepinephrine with histamine and replacing a1A receptor with the h1-histaminergic (h1H) receptor. Here, histamine stimulation of h1H upregulates the enzyme Phospholipase A2, leading to the same release of PC and AA as discussed above [5, 6].
(http://i.imgur.com/cgNJG7z.gif)
We can refer to the cascade of events, starting with simulation of the a1A and h1H receptors and ending with the production of inflammatory eicosanoids, as the POIS Cascade. To cure POIS, you have to modify the POIS Cascade by inhibiting three key events:
1. α1-adrenergic receptor overexpression
2. h1-histamine receptor overexpression
3. arachidonic acid incorporation into phospholipid bilayer
(1) a1A receptor expression is down regulated by the universal methyl group donor S-adenosyl-methionine (SAM-e) by donating its methyl group through methyltransferase enzymes [7]. In this way, SAM-e prevents the breakdown of the phospholipid bilayer [8] and the subsequent metabolism of AA [9].
(2) h1H receptor expression is down regulated by Protein Kinase C (PKC) inhibition [10]. PKC is potently inhibited by thiamine diphosphate, the active form of vitamin B1 [11]. Moreover, thiamine supplementation reduces median histamine levels [12].
(3) AA production and incorporation into the phospholipid bilayer is blocked by the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [4, 13]. Moreover, EPA directly competes with AA for access to enzymes LOX-(5, 9), COX-(1, 2) and the CYP450 group [4]. And unlike AA, the metabolic products of EPA interaction with these enzymes are anti-inflammatory.
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (https://www.amazon.com/Jarrow-Formulas-Promotes-Strength-Enteric-Coated/dp/B0013OVW0O/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1504971308&sr=1-4&keywords=sam-e%2B200mg&th=1) (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---pyridoxine HCl (https://www.amazon.com/Solgar-Vitamin-Tablets-100-Count/dp/B000Z8VGE6?th=1), vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Metafolin (https://www.amazon.com/Solgar-Folate-Metafolin-400-Tablets/dp/B00H7JYKHQ/ref=cm_cr_arp_d_product_sims?ie=UTF8&th=1), vitamin B9 (200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (50mcg) [methyl group cycler]
---Pick from one of the following three methyl group donors:
1. tri-methylglycine (https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_7_s_it?s=hpc&ie=UTF8&qid=1504972619&sr=1-7&keywords=betaine&th=1), betaine (1.5g) [methyl group donor]
2. alpha-glycerophosphocholine (https://www.amazon.com/NOW-Alpha-GPC-300-Capsules/dp/B001RYKA3U/ref=sr_1_5_a_it?ie=UTF8&qid=1504972471&sr=8-5&keywords=alpha-GPC&th=1), alpha-GPC (1.2g) [methyl group donor]
3. phosphatidylcholine, Lecithin concentrate (1.5g) [methyl group donor]
With food, twice daily (fat soluble):
---Benfotiamine (https://www.amazon.com/Life-Extension-Benfotiamine-Thiamine-vegetarian/dp/B000MYXVTQ/ref=sr_1_18_s_it?s=hpc&ie=UTF8&qid=1504972698&sr=1-18&keywords=Benfotiamine), vitamin B1 (150mg) [h1H downregulator]
---eicosapentaenoic acid, EPA (900mg) [AA synthesis inhibitor, AA blocker]
---docosahexaenoic acid, DHA (150mg) [AA synthesis inhibitor]
---vitamin D3 (1000 IU) [AA inflammatory enzyme regulator, IDO/TDO down-regulator] (https://www.amazon.com/MuscleTech-Omega-Black-Onyx-softgels/dp/B01IBQH462/ref=sr_1_fkmr0_1_s_it?s=hpc&ie=UTF8&qid=1504972154&sr=1-1-fkmr0&keywords=Omega+4X+SX7+Black+Onyx)
Note: Many of these supplements have slow diffusion across the blood/brain barrier and/or slow incorporation into the phospholipid bilayer. So it may take 3 to 4 weeks of consistent supplementation before you are able to assess the full benefit. I continue daily maintenance of supplementation with the POIS Cascade Stack even after seeing my symptoms disapear.
About SAM-e: SAM-e plays a unique role in the Homocysteine Cycle (https://i.imgur.com/hq96vF1.jpg) (see #1) and cannot be replaced by any other methyl donor or cycler. SAM-e may upset your stomach the first time you take it; this is normal. Do not take SAM-e within 5 hours of your typical bedtime or you may experience trouble going to sleep.
About Methyl donors: For the alpha-GPC option, start out taking apha-GPC once daily at 300mg and work your way up to a twice daily dose at 600mg over the course of one week. Large doses of alpha-GPC without being acclimated first could cause choline-induced lower-back and upper-leg pain. The advantage of taking methyl donors such as choline and betaine (TMG) is that they offer a folate-independent path (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/) to reducing homocysteine and recycling SAM-e (see #2 in Homocysteine Cycle (https://i.imgur.com/hq96vF1.jpg)). I believe this folate-independent and (MTHFR)-independent SAM-e production by choline/betaine was critical for curing my own POIS symptoms. Di-methyglycine (DMG) does not offer this advantage, and could make problems worse (https://books.google.com/books?id=3K3ECQAAQBAJ&q=%22dmg+is+a+potent+inhibitor+of+BHMT%22#v=snippet&q=%22dmg%20is%20a%20potent%20inhibitor%20of%20BHMT%22&f=false) for those who are undermethylated/folate-deficient.
About vitamin B6: The amount of vitamin B6 here (2mg) is roughly 100% of the US recommended daily allowance (RDA) (https://ods.od.nih.gov/pdf/factsheets/VitaminB6-Consumer.pdf). My daily B6 consumption does not exceed 25mg as an upper limit. However, typical branded B6 and B complex supplements may exceed 200mg (10,000%) and are toxic when taken daily.
About Metafolin B9: I can no longer find my original source for Metafolin (200mcg). Taking Metafolin (400mcg) every other day or breaking the pill in half may be reasonable compromises.
About Omega-3: Because of the way that EPA is metabolized in the body, it does not have any toxicity in the body. So, the more the merrier! DHA has a theoretical toxicity, but this has never been demonstrated in vivo. Omega-3s compete with and are a substitute for omega-6s like AA (https://www.psychologytoday.com/blog/in-the-zone/201204/what-are-the-real-differences-between-epa-and-dha). Therefore, it may be just as important to reduce dietary omega-6 (AA) consumption (https://www.ncbi.nlm.nih.gov/pubmed/9590632). I have almost eliminated certain fatty-meats (i.e. pork and beef) from my diet since this is the largest source of arachidonic acid in North America.
Final note: For those wanting to include herbal supplements, piperine (10mg), from black pepper extract, shortly (~35min) before sexual activity should be effective at inhibiting all of the enzymes that AA interacts with. For those who take medications that interact with COX/LOX/CYP450/TDO/IDO enzymes, please consult a healthcare physician before taking piperine.
I avoid concentrated extracts of curcumin, luteolin, quercetin, ginger, and peppermint because from my experience, these flavonoids (https://en.wikipedia.org/wiki/Phytoestrogens#Structure) reduced the quality and quantity of my semen. I noticed this effect in my semen when I used to take concentrated extracts of curcumin and luteolin. I discovered this by accident about a year and a half ago after taking large doses of curcumin and luteolin. I noticed a slight thinning of my semen and reduced volume. When I stopped taking curcumin and luteolin (daily), after about a week my semen recovered. Thinking that this was a coincidence, I resumed only curcumin (daily), but after a few days I noticed the same effects on reduced volume.
These were not rigorous test, but after some research, I found that flavonoids mimic steroids in the body for their effects. In other words, flavonoids derive their beneficial effects primarily through steroid signaling [15 (http://www.cancersupportivecare.com/estrogenherb.html)] (anti-inflammatory[16], anti-oxidant [17], mast cell stabilizing [18], IDO/TDO inhibiting [19], neuroprotection [20], cAMP-PDE inhibitor [21]). The US Environmental Protection Agency list quercetin as one of the strongest estrogens (https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-estrogen-receptor-bioactivity) found in the environment [22]. However, it is important to point out that whole-herbs like licorice (contains quercetin) (https://benthamopen.com/ABSTRACT/TORSJ-6-1) and tumeric do not appear to have this negative effect (http://www.sciencedirect.com/science/article/pii/S2214750015300652), and I have not experienced any negative side effects on sperm when taking whole-herbs. My concern about using flavonoid extracts is purely out of concern for the health of my reproductive system, and is not related to reducing POIS symptoms. Like steroids, it appears that flavonoids (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851288/) can also potently reduce inflammation and other POIS symptoms. I do make it a point to get natural levels of flavonoids through diet (capers, onions, apples, broccoli, spicy foods, tumeric-based vegetable currys). However, I personally do not take active hormones.
For sperm consistent herbal supplements, I sometimes like taking lycopene, lutein, zeaxanthin, and oils like olive oil, ahiflower oil and/or cinnamon oil. Each of these oils has a unique protocol for supplementation to receive the maximum benefit. Please do the research before you buy.
References:
1. Specificity of the neuroendocrine response to orgasm during sexual arousal in men. (2003) (http://joe.endocrinology-journals.org/content/177/1/57.full.pdf)
2. Norepinephrine stimulates arachidonic acid release from vascular smooth muscle via activation of cPLA2. (1998) (http://ajpcell.physiology.org/content/274/4/C1129)
3. Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism. (2013) (https://www.hindawi.com/journals/ije/2013/361895/)
4. Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms. (2004) (http://ajcn.nutrition.org/content/79/6/935.full)
5. Histamine-induced release of arachidonic acid and of prostaglandins in the peripheral vascular bed: mode of action. (1980)
6. Histamine-induced inositol phospholipid breakdown mirrors H1-receptor density in brain. (1983)
7. Effects of the novel antidepressant S-adenosyl-methionine on alpha 1- and beta-adrenoceptors in rat brain. (1989) (https://www.ncbi.nlm.nih.gov/pubmed/2559855)
8. S-adenosyl-l-methionine inhibits phosphoinositide metabolism in the rat brain synaptosomal suspensions. (1993)
9. Anti-inflammatory activity of S-adenosyl-L-methionine: Interference with the eicosanoid system. (1983)
10. Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-δ/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells. (2013)
11. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. (2003)
12. Effects of thiamine administration on hypothermia and hypothalamic histamine levels in dietary-induced thiamine deficient rats. (1990)
13. The influence of fish oil diet and norepinephrine treatment on fatty acid composition of rat heart phospholipids and the positional fatty acid distribution in phosphatidylethanolamine. (1986)
14. Inclusion of thiamine diphosphate and S-adenosylmethionine at their chemically active sites.
15. Estrogen and progestin bioactivity of foods, herbs, and spices. (1998) (https://www.ncbi.nlm.nih.gov/pubmed/9492350) also link to full article (http://www.cancersupportivecare.com/estrogenherb.html)
16. Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury. (https://www.ncbi.nlm.nih.gov/pubmed/18188998)
17. Antioxidant status and reproductive hormones in women during reproductive, perimenopausal and postmenopausal phase of life. (2014) (https://www.ncbi.nlm.nih.gov/pubmed/25335378)
18. Progesterone Inhibits Mast Cell Secretion (2006) (http://journals.sagepub.com/doi/pdf/10.1177/039463200601900408)
19. Tryptophan metabolism, disposition and utilization in pregnancy (2015) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626867/)
20. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (2013) (http://)
21. Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity. (https://www.ncbi.nlm.nih.gov/pubmed/2177509)
22. Endocrine Disruptor Screening Program (EDSP) Estrogen Receptor Bioactivity (https://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-edsp-estrogen-receptor-bioactivity)
Hello Nanna1,
Just a quick question : Is there any way to verify your theory through blood test ? Any marker that could point out an anomaly ?
So far, as long as I know, no one has been able to find anything abnormal in blood test or exam.
Thanks
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Why would you ever want to remove 'norepinephrine' from your body??? I understand removal of histamine, but norepinephrine is the neurotransmitter that will help your mood, your energy level, social functioning and cognition.
Nanna1, I am challenged to really understand your theory. You have a whole stack of substances that are actively 'increasing' norepinephrine levels (Tyrosine, Quercetin, etc) so noreph should be good and you dont want to decrease something that is good. Off course I understand if you have too much of it, your body cant do its repair process, but I dont see the point, of inflating a tire only to deflate it 5 mins later.
Also the reason I'm interested in Noreph. is that I have been prescribed Vyvanse for my attention deficit, which potentiates dopamine and noreph. levels in your brain and inhibits the absorption by body so it can get recycled more (at least thats the easy way I understood 're-uptake' as).
However, on O days, I am taking an extra TMG (and other water solubles) dose after the orgasm to speed up the removal of histamine and norepinephrine from my body. Methyl donors lower histamine and norepinephrine levels through the homocysteine cycle (http://i.imgur.com/hq96vF1.jpg) [1, 2].
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Hi LAPOISSE,
I'm not sure about what blood test would verify/nullify the POIS Cascade Theory/Hypothesis. My guess would be a low white blood cell count and low gran number since these parameter seem to correlate with methylation B12 status. But again, I'm not sure.
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Hi fathom,
Thank you for your question. I will start with a short background:
- there are 4 histamine receptors (h1, h2, h3, and h4 receptor)link (https://en.wikipedia.org/wiki/Histamine_receptor)
- there are 5 adrenergic receptors (alpha1/a1, a2, beta1/b1, b2 and b3 receptor)link (https://en.wikipedia.org/wiki/Adrenergic_receptor#Categories)
- only the h1-histamine and a1-adrenergic produce inflammation/allergy/sickness (activating arachidonic cascade)
Therefore, histamine and norepinephrine (NORE) are not inherently bad. In fact, all of the receptors h1-h4, a1, a2 and b1-b3 can have positive effects (https://en.wikipedia.org/wiki/Adrenergic_receptor#Subtypes) in regulating bodily functions when they are in right balanced.
The POIS Cascade Theory asserts that POIS is caused by:
1. α1-adrenergic receptor overexpression (imbalance)
2. h1-histamine receptor overexpression
3. arachidonic acid incorporation into phospholipid bilayer
In cases of high stress, it may also be possible that the NR2B-NMDA receptor is over-expressed (https://poiscenter.com/forums/index.php?topic=2502.msg21532#msg21532) as well. When these receptors are over-expressed, an elevation in NORE, histamine and glutamate will cause inflammation and sickness through the arachidonic cascade. This is the POIS Cascade Theory. When discussing the stack, I start from the assumption the receptors are imbalanced without necessarily explaining this.
I apologize if it is confusing which supplements are contained in the stack. The only supplements in my POIS stack are those listed under the bold subtitle "The POIS Cascade Stack: (https://poiscenter.com/forums/index.php?PHPSESSID=muhgc6gv17rrs25ns03f7u7091&topic=2502.msg21497#msg21497)". Other supplements like lycopene and cinnamin oil, I take for general health purposes but not everyday. There are no histamine blockers, quercetin, tyrosine or synthetic drugs in the POIS Cascade Stack. There is nothing in this stack that increases tyrosine or NORE. Both methylation enzymes (COMT and PNMT) can decrease NORE levels (see the bottom of the figure on the right) (https://en.wikipedia.org/wiki/Norepinephrine#Biosynthesis). In healthy people, methyl donors do not decrease NORE below normal levels because of a self-regulating negative feedback on enzymes COMT and PNMT. Through COMT and PNMT, SAM-e can elevate dopamine and epinephrine slightly, but still within normal (non-recreational) levels. However, if you are taking prescription medications to maintain elevated NORE levels, I recommend you consult your doctor or healthcare professional to make sure there are no drug interactions.
Epinephrine (A.K.A. adrenaline) (https://en.wikipedia.org/wiki/Epinephrine) and Norepinephrine (A.K.A. noradrenaline) (https://en.wikipedia.org/wiki/Norepinephrine) control the muscle contractions for orgasm. They also control the muscle contractions for heart beats. During orgasm, adrenaline and noradrenaline are released in pulses from mast cells and peripheral neurons located in the reproductive organs. The resulting contraction produces ejaculation. In healthy people, NORE levels normalized back to baseline within minutes of an O (see second figure) (https://poiscenter.com/forums/index.php?topic=2502.msg21550#msg21550).
Adrenaline and noradrenaline (epinephrine and norepinephrine) cannot cross the blood brain barrier (https://www.google.com/search?q=norepinephrine+cross+the+blood+brain+barrier&oq=norepinephrine+cross+the+blood+brain+barrier&gs_l=psy-ab.3..0i7i30k1.10124.10124.0.11001.1.1.0.0.0.0.88.88.1.1.0.dummy_maps_web_fallback...0...1.1.64.psy-ab..0.1.88....0.bVC0DfFei98). So any elevated NORE that is not metabolized shortly after O will diffuse through the body. Some of it will travel to the heart (increasing heart rate, muscle twitching, etc...) and producing inflammation. Again, this assumes a1 and h1 receptor overexpression.
Unlike NORE, SAM-e can cross the blood brain barrier. SAM-e has a proven track record of elevating mood, reducing inflammation (downregulating a1-adrenergic receptor (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)/ see reference #7) and elevating neurotransmitters (dopamine, serotonin, acetylcholine and epinephrine) in the brain. But please consult your healthcare professional about drug interactions with your medications.
I consider this a pseudo-opensource stack. So please let me know if you have any comments, questions or suggestions for improving it. :)
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Hi Nanna,
So I finally recieved my full pack but it turned out that I forgot about the DHA, I purchesed everything except it. Do you think that'd cause me a problem or do you think that it is manageable without it ?
thx
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Hi Nanna1,
So I am slowly migrating to your prepack. As of last week, I purchased Lecithin and Creatine. I wanted to ask, because you cannot buy SAMe in chemists here, is Creatine a good substitute? Romies mentioned Creatine is cheaper than SAMe also, and a small amount of Creatine ends up preserving a lot of SAMe in the body. What do you think?
I have not totally migrated yet but, I've started taking every day a 1.2g Lecithin pill, a little B1 and a little B6 (by breaking open the pills and taking small amounts), Fish Oil I seem to be taking on average about 5 grams a day (each capsule is 1g containing 180 epa and 120 dha). The recommended amt on the box is between 1-3g per day so I am nearly doubling that. Hopefully it doesnt kill me. You mentioned EPA is fine but DHA is theoretically toxic at certain levels so should I be concerned about this?
Tonight I took about half a folic acid for the B9 component. The tablets are 500mg I think so I took about half. I will start taking approx. 200mg of that twice a day. Assuming folic acid is okay instead of the Metafolin?
The B12 tablet I have is 1000 mcg, no idea how to break that down to 50mcg. Haven't bothered doing that yet. I do have a B complex pill but it only contains 10mcg of B12. I often take a B complex once a day, they are small pills though so it only has a bit of each b vitamin in it.
The D3 pill also I started taking tonight. I live in Australia.and we get heaps of sun but I'll take it anyway to be safe, as I am not in the sun too much.
I mainly wonder about the SAMe...
Thanks for the help.
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To add to the previous post, I just realised that you take 200mg of an enteric coated SAMe. I took a whole big teaspoon of Creatine last week (approx 3 grams) which is apparently equivalent to about 9 grams of SAMe if romies equation of 1 gram of creatine equaling 3038 of SAMe is accurate.
So this ends up being about 50 times more SAMe than you take at a time... Probably not a good idea :)
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Hi Nas,
Thank you for your question. The reason I take omega-3s is to increase the (omega-3)/(arachidonic acid) ratio. If you cannot get omega-3 supplements, there are two strategies worth considering:
- Reducing dietary arachidonic acid consumption. Animal fat is the largest source of arachidonic acid.
- Increasing dietary omega-3. Algae, flaxseeds and fish are some of the largest sources of omega-3.
I added a few more details in the (Notes: About Omega-3:) section of the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) for others who are also customizing the stack without omega-3. I hope this was useful.
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Hi Michael218,
Thank you for your question. If the lecithin pill is a gel capsule you may have to take it with food. I would check the label to make sure.
The theoretical toxicity from DHA comes from lipid peroxidation (free radicals) when DHA is oxidized. According to your post you are taking 5x120mg = 600mg of DHA? One serving of fish will give you about 1g (1000mg) of DHA. So you would be well below toxicity. Also, I have not seen any clinical studies in humans that show this to be a problem.
The folate type only matters if you have MTHFR gene mutations that lower the natural conversion of folate to the active form (5-methyltetrahydrofolic acid, metafolin) in the body. However, I should point out that choline can recycle SAM-e by a folate independent path. I updated the original post in the (Notes: About Methyl donors:) section. In this stack, metafolin is used for redundancy.
B12 has extremely low toxicity. (http://lpi.oregonstate.edu/mic/vitamins/vitamin-B12#toxicity) I do not see any problem with 1000mcg. If you are able to determine that you are not D3 deficient, then I would not worry about supplementing D3. I am one of those people with darker skin. And since melanin blocks light-induced D3 production, I have to take it.
I have seen personal benefits to POIS in the past from taking creatine. However, I am not taking it now. I think creatine (CREA) is an excellent complement to the POIS Cascade Stack as long as you are familiar with how to load it (https://www.bodybuilding.com/fun/anssi1.htm). CREA production consumes choline/betaine-TMG in the liver. And CREA supplementation spares the consumption of betaine by the homocysteine cycles (https://imgur.com/hq96vF1) in the liver. This leaves more choline and TMG available for methyl donation in the liver and improves the liver's ability to detoxify through methylation. However, in the rest of the body, creatine does not spare TMG or choline consumption and CREA is not a methyl donor. So CREA is not a replacement for methyl donors.
SAM-e is the sole methyl donor for more than 40 methyl-group transfer enzymes (methyltransferases) (https://en.wikipedia.org/wiki/Methyltransferase) and cannot be replaced by any substance (natural or synthetic). In other words, there are many SAM-e dependent enzymes that no other methyl-donor can interact with (not even choline). It is important to note that SAM-e is not the source of methyl groups. SAM-e is cycled like folate and B12. When supplementing with SAM-e, you are not increasing the number of methyl-groups by any significant amount, you are increasing the number of parallel homocysteine cycles (https://imgur.com/hq96vF1).
As an analogy, consider the cylinders/pistons in a car engine. SAM-e is the cylinders and TMG is the gasoline. The car cylinders (SAM-e) are cycled and output energy (methyl-groups) each cycle. The more cylinders (SAM-e) you have, the more energy (methyl-groups) you can output per second. Think horsepower. But you still need gasoline (TMG) to make the car run. This is only an analogy and every analogy has its limits. But I just wanted to point out that SAM-e plays a much different role than choline or betaine. So the comparison in terms of methyl-group supplying/sparing should not be between SAM-e and creatine, it should be between TMG and creatine. And TMG (https://www.amazon.com/BulkSupplements-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B00GW6T0O8/ref=sr_1_1_sspa?ie=UTF8&qid=1506754710&sr=8-1-spons&keywords=betaine&th=1) (supplying three methyl-groups) is less expensive, being ~40% the cost per methyl-group of creatine (https://www.amazon.com/Monohydrate-Micronized-BulkSupplements-Performance-Bodybuilding/dp/B00E9M4XEE/ref=sr_1_6_s_it?s=hpc&ie=UTF8&qid=1506754724&sr=1-6&keywords=creatine&th=1) (sparing one methyl-group).
In terms of choline (methyl-group) sparing, there is no advantage to taking creatine instead TMG. However, creatine can have a very big benefit on reducing POIS symptoms as a phosphate cycler managing ATP levels. ATP is required to run the homocysteine cycles (https://imgur.com/hq96vF1) (converting methionine into SAM-e by donating Adenosine). And creatine acts as a phosphate bank, transfering phosphate-groups when ATP is low and accepting phosphate-groups when ATP is too high.
(https://i.imgur.com/EUeRiXV.gif)
In our car analogy, ATP would be the spark plug and creatine would be the battery. It is an imperfect analogy, but the point is that CREA and ATP supply the energy needed to recycle SAM-e and keep the homocysteine cycles (https://imgur.com/hq96vF1) going. This effect of CREA is not limited to the liver and occurs throughout the body. And since ATP is the main energy carrier, the effects of CREA supplementation can extent far beyond POIS.
(https://i.imgur.com/HdSvG68.jpg)
Creatine loading (https://www.bodybuilding.com/fun/anssi1.htm) involves 20 grams/day for 5 days (5 doses of 4 grams). And then the maintenence phase involving a single dose of 5 grams per day. The reason for loading is that the muscles are greedy and can store ~20 grams of excess CREA before saturating. Any CREA that does not disolve in water will not be absorbed by the body and may cause bloating or other stomach problems. Putting a glass of water in the microwave for 30 seconds before adding creatine monohydrate will help it dissolve better and absorb. Other forms of CREA (i.e. tricreatine malate) may dissolve in room temp water. I am not currently taking CREA because of the complexity of the loading phase and carb requirements. Moreover, I used to cycle off creatine for 2 weeks to give my kidneys a break, but got tired of the on-off schedule.
I hope something here answered your question or at least gave you an idea of how to customize your stack. Let me know if you have any new ideas or new combinations that work.
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Hi Nanna,
Very informative post about the role of the different supplements in the methyl cycle. It will be very useful for those building their custom stack of supplement inspired by your method.
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Hi Nanna1,
So I am slowly migrating to your prepack. As of last week, I purchased Lecithin and Creatine. I wanted to ask, because you cannot buy SAMe in chemists here, is Creatine a good substitute? Romies mentioned Creatine is cheaper than SAMe also, and a small amount of Creatine ends up preserving a lot of SAMe in the body. What do you think?
I have not totally migrated yet but, I've started taking every day a 1.2g Lecithin pill, a little B1 and a little B6 (by breaking open the pills and taking small amounts), Fish Oil I seem to be taking on average about 5 grams a day (each capsule is 1g containing 180 epa and 120 dha). The recommended amt on the box is between 1-3g per day so I am nearly doubling that. Hopefully it doesnt kill me. You mentioned EPA is fine but DHA is theoretically toxic at certain levels so should I be concerned about this?
Tonight I took about half a folic acid for the B9 component. The tablets are 500mg I think so I took about half. I will start taking approx. 200mg of that twice a day. Assuming folic acid is okay instead of the Metafolin?
The B12 tablet I have is 1000 mcg, no idea how to break that down to 50mcg. Haven't bothered doing that yet. I do have a B complex pill but it only contains 10mcg of B12. I often take a B complex once a day, they are small pills though so it only has a bit of each b vitamin in it.
The D3 pill also I started taking tonight. I live in Australia.and we get heaps of sun but I'll take it anyway to be safe, as I am not in the sun too much.
I mainly wonder about the SAMe...
Thanks for the help.
Hi Michael,
EPA and DHA are quite safe, but just monitor for their potential effect on blood thinning if taking high doses for a long time. If you have signs of coagulation function impairment, like easy bruising, nose bleeding, excessive bleeding if minor cuts, or the like, stop for a time, and adjust the dose downward when resuming omega-3 supplementation ( Placing safety first, do not hesitate, to consult a health professional about your Omega-3 dosage, in particular of any of these warning signs happens )
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Thanks Quantum for mentioning the possible blood thinning effects of omega-3. That is correct that blood thinning could be an issue, especially for those taking certain medications. Here is a list of possible drug interactions:
http://www.umm.edu/health/medical/altmed/supplement-interaction/possible-interactions-with-omega3-fatty-acids
But as you said, we should consult a healthcare professional if these problems arise.
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Hy Nanna
I just realised that I was completly lucky. The EPA pack turned out to contain Omega 3 in it, in a ration of 4:1 out of 1000mg pills. That's very close to your recomendation as well lol.
But I do have another question. Given how this pack is kinda pricey and it's not easy to ship stuff from the US to here ( I live in Iraq ), and stuff is REALLY expensive ( pack total was about 200$). Is there any less important supplements I can get rid off ? or a way that I can decrease my daily usage to less than two times a day ?
thx
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Oh and the Bentofetamine is 250 mg capsuls, so I won't take them twice a day.
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Nanna, Quant... thanks for your awesome replies. Nanna i'll need a few thousand years of enlightenment before i can digest everything you have written - i just skimmed through it for now and will try to make sense of it a bit later. The terminology really throws me off - i am terrible at remembering this stuff but should make it my business to.
I will say this.
Last week as mentioned, I started taking Lecithin daily, a little creatine (1/10th of a teaspoon fully dissolved sweetened powder in water twice a day). I broke the B1 B6 and B12 pills into tiny pieces and had a tiny bit of each twice a day prior to orgasm. I also packed in the fish oil, about 5g a day as 3 separate doses.
Had sex 2 nights ago, and my symptoms have pretty much disappeared. No anxiety which is normally what gets me the worst. Perhaps very slight mood symptoms...
Anyway probably my best result in a while - 85%-90% reduction in symptoms. Barely noticed anything different. Very pleased with this weeks result. Who knows though, could be due to timing of my orgasm after the prepack (1.5 hrs after), what was eaten that day, etc... will definitely keep moving towards your cascade stack... obviously will need to purchase some SAMe.
Thanks again!
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Great results, Michael! You are on the right track for sure, 80%-90% relief is excellent.
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Thanks Quantum! It is great having you here in this forum. Very grateful to have you here!
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Hi Nas,
I realize that price is a major issue for parts of this stack. I have been trying different things to reduce the cost of the daily stack. The economics favor prepacks over a daily regime like the POIS Cascade Stack since with a prepack you are taking supplements less often. However, those who experience POIS probably also experience other negative health effects associated with inflammation that are more subtle and longer lasting than post-orgasm illness. So long-term health would favor a daily regime. But maybe there is some middle ground worth exploring. I am trying some new ideas in hopes of getting the cost down, but I will wait until I get results before sharing.
In terms of the POIS Cascade Stack, you can probably get the most effect for your money from (SAM-e, B6, Lecithin) along with a reduction in dietary arachidonic acid (AA). AA is primarily stored in certain animal fat. To see how to reduce food intake of AA see the (Notes: About Omega-3:) section in the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497).
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Thanks Quantum! It is great having you here in this forum. Very grateful to have you here!
Ditto!
:)
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Thanks Quantum! It is great having you here in this forum. Very grateful to have you here!
Ditto!
:)
Thanks for your words of appreciation, guys :)
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Nanna, so you mention you take:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---pyridoxine HCl, vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Metafolin, vitamin B9 (200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (50mcg) [methyl group cycler]
---Pick from one of the following three methyl group donors:
1. tri-methylglycine, betaine (1.5g) [methyl group donor]
2. alpha-glycerophosphocholine, alpha-GPC (1.2g) [methyl group donor]
3. phosphatidylcholine, Lecithin concentrate (1.5g) [methyl group donor]
With food, twice daily (fat soluble):
---Benfotiamine, vitamin B1 (150mg) [h1H downregulator]
---eicosapentaenoic acid, EPA (900mg) [AA synthesis inhibitor, AA blocker]
---docosahexaenoic acid, DHA (150mg) [AA synthesis inhibitor]
---vitamin D3 (1000 IU) [AA inflammatory enzyme regulator, IDO/TDO down-regulator]
Few questions if i may.
1) you put B6 2mg-25 mg twice daily. Confused, how much is each separate dose?
2) how much fish do you eat regularly in your diet? I basically eat none. Never been keen on fish at all. Will i need to supplement more if i do not eat any fish?
3) you put 900 mg of EPA twice daily- does that mean you take 1800 mg per day, or did you mean 450 mg ? 2 doses? Same with the others, you put 200 mg of SAMe twice daily, a total of 400 mg SAMe per day?
4) I have been taking everything you mentioned for about 2 weeks now. If I slowly introduce SAMe into the stack next week, how long should it take before it gets the best results? I currently take my own prepack but only prior to orgasm so i would like to test your stack without the aid of my current prepack eventually...
5) hows your prepack working for you now? How many o's are you able to have weekly without symptoms at the moment?
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Hi Michael218,
Sorry for the delayed reply. I have not been on the forum this week.
- 2mg - 25mg is a range for a single dose. I have personally used single doses in that range. There is a brief discussion about this in the (Note: About vitamin B6: ) section of the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497).
- I do not eat fish on a regular basis. I might eat fish once a week (single meal) or once every other week.
- The EPA dose I am using is 2x900mg, so 1800mg per day. The SAMe dose is 2x200mg, so a total of 400mg per day. However, I some times find it hard to get the second SAMe dose in, since I am at work and it needs to be taken on an empty stomach. So many days I only do a single SAMe dose, but on an orgasm day I always make sure to get the second dose in. It is kind of a cheat on the SAMe dosing.
- I would say that 1 month of supplementation is a good time point to judge whether the stack is working for you.
- The stack works the same now as always. I do not orgasm that often, maybe twice a week. My only symptoms are drowsiness. I tend to fall asleep quickly right after an orgasm. But when I wake up, I have plenty of energy.
Thanks for the question.
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Hello, Nana! Question? There Pois 7 people, and they passed tests for hormones. Everyone has a common, this is increased progesterone and cortisol. What do you think about it? What treatment can be done? And I think many of those who took tests from this forum similar. Thanks! Sorry for English.
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Hey Nanna,
So I would like to fill you in on my 3weeks of supplementation with this pack. On the first day I tried the empty stomach stack, I orgasmed after it within 3 hours, and boy oh boy it was the first time I ever felt that I have been even remotly reliefed of at least 20% of my symptoms. I noticed that I was able to speak with some form of consistency without stutering that much, which wasn't the case in the past.
And so I continued the supplementation, and as I mentioned because the pack is a bit too expensive, I decided to trade money with time, so I only take them once a day (even on orgasm days), so that would probably mean that I won't see the full effect for about two months ? ( does it work like that ? ) Still the biggest effect I noticed besides the about 50% relief, is that on day to day basis I started noticing a huge difference socially, I became more connected with people and generally calmer and more interactive, still not 100% obviously but it's definitely much better. I still suffer from congnitive issues though such as memory problems, multitasking and short attention span.
One thing that I noticed is that every single supplement I take, I feel energized right away after taking, but it's not the case with the GPC, as taking it causes intial brain fog and taking the full 1.2 even starts showing some sensetiviry problems. And that's why I orderd lecithin instead, as it is generally less symptoms inducing than the GPC I think.
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That's great, Nas! I am happy that you have finally found a way to reduce your POIS symptoms, at least in part.
With time, and by fine tuning your regimen, your percentage of relief will surely get better. You are on the right path :)
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Thank you Quantum, Hopefully I am :D
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Hello.
I take the stack of Nanna. I feel good. I noticed that communication with people is much easier. I began to speak well and my memory improved. But now strange things happen to me. I've been abstaining from O. for about two weeks already. I noticed that my memory is progressing. But my skeleton got sick. I feel that my bones are brittle. But as soon as I did not take the TMG, I again felt good, but my memory and speech became a little worse. Do not you think that this is a reaction to the dying of a fungal infection? I need your advice. What do i do?
is it possible because of the lack of vitamins B? I now practically do not use them :(
all the best,Rinat
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Folks, I have been busy for last 1 month getting myself treated at Cleveland clinic while same time increasing my vitamin stack sourced from this forum. I learnt a couple of things specific to my various conditions, and might be that they are helpful to you, since I'm increasingly seeing a pattern of all people here. Also I have a few questions in particular from Nanna1
To set baseline, my symptoms are much more severe than most people on this forum, in that while the POIS 7-day period makes my symptoms worse, however 1/2 of my symptoms are chronic and present 24x7 regardless of having or not having an o, but they are closely related in the sense that they are neurological in nature.
1. I think Sam-e and Choline supplement has done wonders for me. My face paresis (post car accident) has disappeared since last 2 weeks. I'd say safely 90% improvement (for the first time in my life)
2. My voice and speech lethargy/fatigue symptoms have not shown visible improvement, maybe 5-10% improvement.
3. I learnt from Cleveland that I dont have any acid reflux, the Bravo endoscopy and other studies revealed a perfect stomach and throat pH and reflux events even less than the larger healthy population. The docs didn't say it, but I felt they were saying to me, its all in my head and the sooner I forget about acid reflux in particular the better. They did diagnose me with chronic low-grade depression (called dysthemia) and chronic generalized anxiety (GAD) and mild disphonia.
General every day med stack:
Sam-e (200mg x 2)
Alpha-GPC 600 mg (or Phosphtadyl Choline 420 mg on certain days I would rather take the slippery PC softgels)
EPA 400 mg / DHA 200 mg
Multi-vitamin (I'm taking an expensive brand 'whole foods Men's +40 multi' - even though I'm not close to 40 yet.
About every other day: Nettle Leaf 225 mg and sometime Quercetin 500 mg with Bromelain 150 mg.
Prescription meds: Vyvanse 70mg (its like adderral) and Gabapentin 100mg (for anxiety)
Pre-POIS: (I think my POIS period has shrunk from 7 days to 6 days)
General stack + Benadryl 25 mg + Quercetin 500 mg with Bromelain 150 mg
QUESTION 1: What should be next that I add to my stack ... my most pressing concern is really my "speech/voice fatigue"? This speech/voice fatigue kicks in daily around Noon and lasts till bed time. On waking up my speech/voice are back to normal and starts to degrade as day progresses.
QUESTION 2: I am intrigued by Sam-e which works closely with choline, and you mention to slowly increase AlphaGPC otherwise it could cause back pain or upper leg pain. Would there be an explanation of why this happens? Reason I ask, I try to lift weights and do cardio like kick boxing, though lately my legs or ankles or thighs are getting swollen on kicking harder and I'm wondering if it is anyway related to anything I'm doing not the best way (swelling comes first, and then as I rest for few days, swelling starts to moved downwards and turn into a bruise ... it all recovers to normal in 3-4-5 days)
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About Question 2, no he said that about the alpha gpc not the sam-e.
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true Nas, I was going to correct/edit it : )
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Hi, Nas, Fathom, Rinat, ans others,
I am happy to see that many members find relief with Nanna's stack. Omega-3 are a great supplement, in my opinion, and SAMe is very beneficial for anyone needing methylation support, among other things. It is sad that the major problem with SAMe is its price, but with years, it tends to get lower.
Keep the forum updated with your experiences, guys !
I would like to point out, for all the members following this thread, that in some cases, reaction to SAMe may be negative, if methylation is already too high. So, it is well to start slowly, with low doses. At any rate, omega-3 can be taken anyway, even when SAMe is not well tolerated, because EPA and DHA form these omega-3 fatty acids are beneficial on their own.
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Hi Quantum, I think my neurological problems are related to methylation. You are right on caution, and thats why I am a little cautious, I am getting great/amazing results so far with using Nanna1's partial stack, though I see few complications as well (getting injured, swollen and bruised easily, but that could be unrelated to the stack I'm taking). I wish Nanna1 was more "present here" : )
From his stack, what I am currently missing is:
1. Benfotiamine Vit B1 (an h1H down regulator) ... though my multi-vitamin does have Thiamin as Thiamin HCl from Culture Media, 2 mg which is 113% of DV. I dont know why Nanna1 has 150mg of Benfo, that seems tooo high?
2. Metafolin Vit B9 200mcg (a methyl group cycler ... though my multi-vitamin does have twice the amount 400 mcg of Folate as Folic Acid )
3. Vit D3 1000 IU (AA inflammatory Enzyme regulator ... though my multi-vitamin does have equal amount 1000 IU of Vit D2 in form of Ergocalciferol)
I am thinking maybe the leg swelling is due to missing a compound (or maybe I'm taking too much compound) that is supposed to regulate some critical chemical that might be getting otherwise out of whack?
b/w: I dont know where you live Quantum, in the US SAMe, I purchased from Amazon, its 'Now' brand 200 mg, 60 tablets for I think $23, certainly not cheap but not exorbitant. I am hoping long-term if all this works, we can gradually wean off these things ... I dont know how that will work :) If you are in closer to Russia, I have seen some hard-to-find nootropics advertised on their websites for like $7.
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Hi Fathom, thanks for your feedback.
About Nanna's presence here, he told in a previous message that things were picking up at work and would be less present here ( see at the end of http://poiscenter.com/forums/index.php?topic=2502.msg21550#msg21550 ). However, he keeps on loging here about once a week.
About Folic acid vs methylfolate, a good percentage of the population have low activity in the biological pathway by which folic acid is converted to methylfolate, the active form of folate, so taking methylfolate directly is better. It is also better to take it along with b12 ( best if methylcobalamin form of B12) to avoid the so called "methyl trap", where methylfolate can cause more harm than good, for some particular mix of SNPs.
About SAMe price, 23 $US is a very good deal for 60 caps of 200mg. Prices go a little bit lower every year. I live in Canada. I have checked the site, and with delivery, plus exchange rate, that would be 38 $CAN for me, from this same amazon.com vendor ( on amazon,ca, best price is over $50 for the exact same product....). As you said, it is not cheap, but not exorbitant. for those who get relief from POIS with this supplement, it is worth the price.
In my personal case, I very badly reacted to methylfolate supplementation, about 2 to 3 years ago, so I may not be under-methylated but over-methylated, and may also react negatively to SAMe. My reaction to methylfolate was no better than POIS itself, with 2 to 3 days of intense fatigue, even with low doses, so I didn't insist, after 3 tests, the last one with a small dose of 50mcg. My baseline anxiety level was still fairly high 3 years ago, so that may explain a part of the reaction, but now that I have a stable, efficient way to control my POIS, I do not feel like challenging this result...hehe. However, I have no problem eating greens, so I get methylfolate through veggies and fruits, in my green smoothies, and tolerate it very well, and I am satisfied with this.
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Hi Rinat,
In relation to your question about brittle bones,
Hello.
I take the stack of Nanna. I feel good. I noticed that communication with people is much easier. I began to speak well and my memory improved. But now strange things happen to me. I've been abstaining from O. for about two weeks already. I noticed that my memory is progressing. But my skeleton got sick. I feel that my bones are brittle. But as soon as I did not take the TMG, I again felt good, but my memory and speech became a little worse. Do not you think that this is a reaction to the dying of a fungal infection? I need your advice. What do i do? Is it possible because of the lack of vitamins B? I now practically do not use them :(
all the best,Rinat
Last Edit: October 25, 2017, 08:53:45 AM by Rinat
Let me start with a little background. Human Growth Hormone (HGH) and insulin-like growth factor 1 (IGF-1) are two hormones that increase bone growth, while cortisol decreases bone growth. Vitamins B6 and B12 increase Human Growth Hormone (HGH) and insulin-like growth factor 1 (IGF-1) partly by increasing the liver production of taurine (Vitamin B12–dependent taurine synthesis regulates growth and bone mass (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071367/)). Betaine (TMG) increases IGF-1 and decreases cortisol production in response to exercise (Betaine supplementation enhances anabolic endocrine and Akt signaling in response to acute bouts of exercise. (https://www.ncbi.nlm.nih.gov/pubmed/22976217)). Both Choline (lecithin) and Vitamin D3 increase bone density and strength (Dietary Choline Intake Is Directly Associated with Bone Mineral Density in the Hordaland Health Study. (https://www.ncbi.nlm.nih.gov/pubmed/28275104)). Omega-3s tend to increase bone density, while omega-6s tend to decrease bone density (The impact of omega-3 fatty acids on osteoporosis. (https://www.ncbi.nlm.nih.gov/pubmed/20041817)). You might be getting brittle bones, but it is not clear which supplement (if any) would be associated with this. Significant changes in bone density usually take years. But if there is a concern about bone density, I would recommend getting a Bone Density Test (x-ray) from a physician.
My guess is that you are experiencing symptoms of dehydration (TMG is an osmolyte (https://poiscenter.com/forums/index.php?topic=2502.msg21858#msg21858)). When dehydrated, the lubrication in the joints of the bones is reduced which can cause the bones to not move smoothly and feel weak. This is different from a change in bone density and can be reversed with sufficient water consumption (https://poiscenter.com/forums/index.php?topic=2502.msg21858#msg21858). I hope something here was helpful.
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Hi fathom,
In relation to your Oct. 23rd post (http://poiscenter.com/forums/index.php?topic=2502.msg22061#msg22061), I assume your multivitamin contains vitamin B12 and D3. If not, those would be the next additions that I would make to your stack. Also, I take more omega-3 than is in your stack. I realize that omega-3s are expensive. I read somewhere that L-taurine efficiently decreases arachidonic acid (an omega-6). I haven't experimented with taurine, so you will have to figure it out if you want to try taurine instead of increasing omega-3. However, taurine is an osmolyte (https://poiscenter.com/forums/index.php?topic=2502.msg21858#msg21858) and requires a lot of water consumption to be effective.
Also I think that drinking sufficient water would help with your voice fatigue and wound healing (see previous post link 1 (https://poiscenter.com/forums/index.php?topic=2502.msg21858#msg21858) and link 2 (http://poiscenter.com/forums/index.php?topic=2502.msg22089#msg22089)). A topical glucocorticoid (over-the-counter) or progesterone (prescription) cream could help temporarily reduce swelling. However, repeatedly injuring the same locations on the leg will lead to a worsening of symptoms over time especially if you do not fully recover between injuries.
Wound healing can be controlled by hormones like testosterone and progesterone. Some times as we age, our hormone levels drop. Pregnenolone sulfate is the quickest way to boost hormone levels. It is a prohormone in that it is not active on its own but requires conversion into other hormones to have an effect. However, I personally recommend cooking with curry powders and spices (frying the spices in oil before adding other food ingredients) and eating cruciferous vegetables (https://poiscenter.com/forums/index.php?topic=2431.msg20521#msg20521). Spices (cumin, oregano, thyme, tumeric, ginger) and cruciferous vegetables should help speed wound healing.
Also, may I share a little trick I have learned for reducing inflammation directly on the skin/joints/muscle:
- fry 1 teaspoon of curry powder (cumin, oregano, thyme, tumeric, ginger mixture) in 1 tablespoon of oil (canola) in a small pan on medium-heat for 2 to 5 min
- when the curry/oil mixture cools to room temperature, mix in 5 drops of eucalyptus essential oil (high in eucalyptol) (https://www.amazon.com/Lily-Lush-Eucalyptus-Therapeutic-Aromatherapy/dp/B0732Q3222/ref=sr_1_6_s_it?s=beauty&ie=UTF8&qid=1509418537&sr=1-6&keywords=eucalyptus+essential+oil) and 5 drops of lemon essential oil (high in limonene) (https://www.amazon.com/Artizen-Lemon-Essential-100-NATURAL/dp/B06Y2BJH9K/ref=sr_1_3_sspa?s=beauty&ie=UTF8&qid=1509418612&sr=1-3-spons&keywords=lemon+essential+oil&psc=1)
- then rub into the skin near the place of inflammation for ~20 seconds
Frying the spices allows for the fat soluble parts of the spice to dissolve into the oil. After frying, you can separate the oil from the spice (starch, fiber, cellulose). The main active ingredient is the eucalyptol from the eucalypus oil. So if all you do is mix eucalypus oil with canola oil, it should still work. Eucalyptol is used extensively in the dentistry profession to numb pain, reduce inflammation, speed healing and inhibit the coughing response. Limonene functions similar to eucalyptol. In my opinion, this is more effective than topical glucocorticoid for local injuries in skin/joints. I hope something here is helpful.
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If i keep vitamin d to 400 ius a day, is that okay, any more it start to keep me from going to sleep at proper times
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Nanna, thanks for your answer. Recently I used vitamin b12 -9 mcg, b6-6 mg, thiamine-5 mg and Glycine-300 mg. My fatigue and back pain almost disappeared :)
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That's great Rinat! I'm glad you solved the issue. I'm sure your solution will help others. :)
That's fine certainlypois2 (400 iu of vitamin D3), Some people get enough vitamin D3 from sun (UV light) exposure or dairy products. I think the most important thing is to not be D3 deficient. I typically take my D3 with with the omega-3s at breakfast and lunch, but not close to bedtime. :)
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He Nanna
I asked you previously about weather taking the two stacks only one time a day even on orgasm days to save money is ok ? and if the two times a day stacks may take a month to show full potential, will that mean that taking them only once a day would take two months to show full potential ? or do I need to take them two times for full effectivness ?
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He Nanna
I asked you previously about weather taking the two stacks only one time a day even on orgasm days to save money is ok ? and if the two times a day stacks may take a month to show full potential, will that mean that taking them only once a day would take two months to show full potential ? or do I need to take them two times for full effectivness ?
Hi Nas,
I could be wrong, but I can only see that strategy working if the biological half-life (https://en.wikipedia.org/wiki/Biological_half-life) of the supplements in the blood was 2 months. For the general public, I'll just mention that the "half-life" is a math-model of exponential decay which is pretty accurate for making quick approximation for blood levels of drugs. The water-solubles usually have a half-life that is on the order of a few hours. Vitamin B12 is the exception in that its half-life in the blood is about 5 days. Fat-solubles tend to have a half-life on the order of a few days.
The main point is that you need equal blood levels of the supplements to get equal effects. For example, vitamin D3 has a half-life of 15 days (https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/). We can do a linear approximation and say a single dose of D3 at 2000IU over one week will produce similar blood levels of D3 as two doses of 1000IU (taken 7 days apart) over 2 weeks. However, after the half-life time point (15 days), this linear approximation to the "half-life model" is no longer good because in reality the D3 blood levels are decaying exponentially. This is a hypothetical example since in the actual stack, D3 is taken daily.
(https://www.uspharmacist.com/CMSImagesContent/2010/10/_USP1010-VitD-T2.gif)
So I would think that the short half-lives of supplements prevent a linear conversion of blood levels and effectiveness from 1 month to 2 months as you have proposed. However, your idea is worth trying. While I believe from my experience that both doses have to be taken daily, it could be that I am taking more of one of the supplements than what is necessary to get POIS relief, and you may find a lower effective dose. Please share anything you find out from any modifications to the POIS Cascade Stack. I may try it and lower the dosing in the original post. :)
Here is an example of how half-life is interpreted for carbon dating:
(https://www.sciencelearn.org.nz/system/images/images/000/002/093/full/Radioactive-decay20160929-23355-1ys4r4j.jpg?1475120031)
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Hi Nanna
That's very interesting but it's been a month and I still have symptoms after masturbation. Social situation is continuing to improve though slowly but surely, same for cogntive. It's probably because masturbating once a week is helping in accumilating the posative effects, but generally I think when I feel that the symptoms are completely halting and not improving is probably where I'll start doubling down. Plus I'm waiting for the lecithine to arrive because I only take 600mg of GPC due to its strong side effects that I wish to avoid.
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Nanna, I received a message from yet another POISCenter Member. He’s having good results thus far with your method!
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Hi nanna1, your solution is really impress. My main POIS symptoms are fatigue, tired/dry eyes and hard to concentrate, memory problem. May I try these supplements?. Thanks.
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hi Nanna1, your tips are very useful. Question:
If I start using DMEA 100mg every day. Do I still Alpha-GPC 600mg daily (which I am right now)?
The DMEA I hear recommended dosage is like 25 - 50mg daily, though I'll be taking 100 mg daily.
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hi Nanna1, where are you now, we miss u much :'(
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Nanna, I received a message from yet another POISCenter Member having good results thus far with your method!
Hi demografx, thanks for passing the info on! :)
Hi codeguy, feel free to try the stack. Just remember to drink plenty of water with the water soluble supplements. ;)
hi Nanna1, where are you now, we miss u much :'(
Sorry I have been very busy with work, so I don't have the time to post consistently. I currently have collaborations with 3 different research groups (3 separate/simultaneous projects). And I am trying to get my own research interest funded. Lots of work. Thanks for asking
Hi fathom, Thanks for the question. I have had bad experiences with both DMEA and Centrophenoxine (DMEA-pCPA). They consistently caused me psychological depression at 500mg-600mg daily. Other people have also reported depression from these supplements as well. I know you are taking 100mg, but I'm not sure what effect this smaller dose would have. It could be that the 25 - 50mg range is a sweet spot of POIS benefit without depression, but I'm not sure.
When taking DMEA, consider the methyl group math
There is a popular myth on the internet that DMEA (Di-Methyl EthanolAmine, 2 methyl groups) increases choline production. I could not find any research articles to back this claim up. DMEA, which only has two methyl groups, cannot increase choline (3 methyl groups) without receiving a methyl group from TMG (Tri-Methyl Glycine, 3 methyl groups).
(supplement name, #methyl groups, #phosphate groups)
- CDP-choline, 3, 2 (https://en.wikipedia.org/wiki/Citicoline)
- alphaGPC, 3, 1 (https://en.wikipedia.org/wiki/Alpha-GPC)
- phosphatidylcholine, 3, 1 (https://en.wikipedia.org/wiki/Phosphatidylcholine)
- TMG/betaine, 3, 0 (https://en.wikipedia.org/wiki/Trimethylglycine)
- Centrophenoxine, 2, 0 (https://en.wikipedia.org/wiki/Meclofenoxate)
- DMAE, 2, 0 (https://en.wikipedia.org/wiki/Dimethylethanolamine)
- creatine, 1, 0 (https://en.wikipedia.org/wiki/Creatine)
If you take large doses of DMEA the body will use your the natural reserves of TMG/betaine in the liver to donate a methyl group to DMEA. So, I do not consider DMEA a methyl donor. In fact, it could negate the effect of methyl donors like TMG. Moreover, the choline produced in the liver cannot cross the blood-brain-barrier.
The only benefit that I see from taking DMEA orally is that it is a structural part of the phospholipid bilayer (see original post). But then again, so are phosphatidylcholine and alphaGPC.
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Thanks nanna1, I'm using anti-depression which is 100mg sertraline each day. Is it OK?
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Thanks nanna1, my post might have some inaccuracies which lead you to it, but I am referring to DHEA and not DMEA which I think are quite different. So if I do try DHEA (100mg), I can keep taking AlphaGPC as normally right? or are you saying that DHEA harmful effect to choline absorption are significant that I must not use it concurrent.
nanna1, I cannot help thank you, you are wizard and have helped me on my paresis issue that no doctor has had. I wish you so best. One VERY important question if you please do address this one to your best: I am considering to use this DHEA solely for a weird reason it may seem to others. But I am very timid/fearful/sensitive in real-world (which I hate very much). It is the root-cause of all the stresses/anxieties which have played havoc with my health, POIS, gastric issues, fatigue, etc. This timidity/fear/sensitiveness to even minor events is also root-cause of my speech issues. I read a research that fearless or resilient or brave people have even higher surges of stress harmones (cortisol and noradrenaline) than normal population. What is chemically unique about them is that they have high levels of DHEA (which mutes the negative aspects of daily and situational stress, while keeping the positive aspects of stress). This resilient and brave people also have high levels of Neuropeptide Y which binds to noradrenaline, preventing the negative aspects of noradrenaline while allowing it to keep amping up their performance.
However since, Neuropeptide Y is still being researched and not available for human use I think, DHEA is a common supplement and its safe for human consumption and body builders use it, therefore it is one thing I can try to get brave :) Do you agree with this bravery hypothesis? Or do you have other suggestions? (FYI: I do take Vyvanse 70mg for my Attention Deficit (which primarily increases dopamine and somewhat noradrenaline in brain) and that helps me become a little confident, but its not enough effect).
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Hi codeguy, I do not know much about prescription medications and I am not a medical doctor. So I cannot comment on specifically on sertraline. Sorry about that
Hi fathom, I do not know of any significant interactions between DHEA and alpha GPC. Both of them are produced and stored by the body in some quantity independent of whether you supplement them. However, pregnenolone is safer and probably more effective than DHEA for POIS related symptoms. I have taken pregnenolone and can vouch for its efficacy against POIS and other forms of inflammation. I do not take it currently (why add another pill?). Pregnenolone is safer because it does not have its own receptor, It is instead converted to active steroids (DHEA and progesterone) when hormone levels become low or stored as inactive steroids (DHEAS and PREGS) if hormone levels become high. (see bolded hormones in the below figure)
(https://i.imgur.com/4tOUktk.jpg)
I personally would not supplement with hormones on a daily basis (except vitamin D3). I only tried pregnenolone briefly as a one-pill prepack.
Neuropeptide Y might not ever be available in pill form because it is a peptide (string of amino acids). Peptides longer than three amino acids usually do no get absorbed intact from the intestines to the blood stream. Peptides are usually injected.
The most effective OTC supplement to eliminate fear that I know of is methylene blue. It works primarily by directly and indirectly boosting the body's energy production efficiency.
- Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. (https://www.ncbi.nlm.nih.gov/pubmed/25018057)
- Methylene blue facilitates the extinction of fear in an animal model of susceptibility to learned helplessness. (https://www.ncbi.nlm.nih.gov/pubmed/17011803)
- Preventing the return of fear using reconsolidation updating and methylene blue is differentially dependent on extinction learning (https://www.nature.com/articles/srep46071)
- Extinction Memory Improvement by the Metabolic Enhancer Methylene Blue (http://learnmem.cshlp.org/content/11/5/633.short)
- Enhancing Extinction Learning in Posttraumatic Stress Disorder With Brief Daily Imaginal Exposure and Methylene Blue: A Randomized Controlled Trial. (https://www.ncbi.nlm.nih.gov/pubmed/28686823)
I personally drink methylene blue if I have to give a talk. Drinking it ~30min before a presentation helps to remove stage-fright and it also helps me recall the info that I am speak about. It is a weird phenomenon to experience, but I feel almost fearless on methylene blue and my capacity for handling stress is much greater. I mixed my own methylene blue solution using about 1/4 the concentration as this guy ->http://www.brainprotips.com/methylene-blue-nootropic/ (http://www.brainprotips.com/methylene-blue-nootropic/) (scroll down). My powder source is here (https://www.amazon.com/IBI-Scientific-IB74050-Methylene-Stain/dp/B0074NYI2M/ref=sr_1_cc_2?s=aps&ie=UTF8&qid=1512257682&sr=1-2-catcorr&keywords=methylene+blue+powder). But if you are not used to measuring powder, then just buy a prepared solution Methylene Blue Solution (30 mL) (https://www.bluebrainboost.com/p/methylene-blue-nootropic/).
Fear Extinction Coctail (mix inside of a clear container/water bottle):- 3 Tbs of lemon juice 100%
- 1 cup of apple juice
- 1 drop of methylene blue
- Expose to direct sunlight for 1 minute
- Optional add on: niacinamide (100mg to 500mg)
With all that said, methylene blue does not help my POIS symptoms. Also, it is a mild MAOI, so there is possible interaction with other MAOI and SSRI.
Two other options for fear reduction that I am aware of:
- h1-histamine blockers like Allegra can also help reduce fear before a performance.
- journaling, writing down your fears and other emotions (this one has a lot of research behind it)
I hope this helps.[/list]
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Hi nanna1, I decided to try your solution even if it's risk. I can't live with my current state. My eyes are dry, burning, fatigue, tears alot esspecially when working with computer. Feel like when i have flu and still trying to focus the screen (only on eyes).
I notice that it's worse after an orgam and 3-5 days after that O too. Some days it suddenly becomes better so I can work with computer very well these days.
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The most effective OTC supplement to eliminate fear that I know of is methylene blue. It works primarily by directly and indirectly boosting the body's energy production efficiency.
(...)
I personally drink methylene blue if I have to give a talk. Drinking it ~30min before a presentation helps to remove stage-fright and it also helps me recall the info that I am speak about. It is a weird phenomenon to experience, but I feel almost fearless on methylene blue and my capacity for handling stress is much greater. I mixed my own methylene blue solution using about 1/4 the concentration as this guy ->http://www.brainprotips.com/methylene-blue-nootropic/ (http://www.brainprotips.com/methylene-blue-nootropic/) (scroll down).
(...)
With all that said, methylene blue does not help my POIS symptoms. Also, it is a mild MAOI, so there is possible interaction with other MAOI and SSRI.
Considering that members here are often taking antidepressant medication, and may also use OTC herbs like St-John-Wort, I have to state that there is a CHANCE FOR SEVERE INTERACTION WITH METHYLENE BLUE
There is also a high potential for interactions between certain food and methylene blue.
So, any member must thoroughly read the following warning form FDA, and consult with a health practitioner before using methylene blue:
https://www.fda.gov/Drugs/DrugSafety/ucm276119.htm
and also, for the food to be avoided with methylene blue, which is a MAOI, see:
https://www.mayoclinic.org/diseases-conditions/depression/expert-answers/maois/FAQ-20058035
The fact that nanna1 does not take any serotonin-related drug, or never had any problem or interaction with methylene blue vs food or medication while using it from time to time, does not mean that another member will not have any problem with it either. In some cases, a member could end up with a bad reaction, and some cases of serotoninergic syndrome, a very severe reaction, have been reported when combining methylene blue with drugs acting on serotonin. Note that those severe reactions usually occur following intravenous methylene blue administration , but caution is advised. So, safety first, consult with your physician or health advisor before trying any methylene blue, even at low dose like what nanna1 is taking.
See also this thread from 2014 for more information: http://poiscenter.com/forums/index.php?topic=1551.msg14569#msg14569
It is clear that nanna1 has nothing but good intentions, and that the doses he takes are low compared to intravenous methylene blue administration, but what is suitable for one person may be dangerous for another. For example, a measuring error lin the preparation, leading to a large intake of methylene blue, could lead to a dramatic result.
[/list][/list]
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Thanks much nanna1. The diagram for DHEA is beautiful (I cancelled my order), it made me realize that it also increases DHT levels. And since I'm taking DHT-inhibitor (Finesteride for hair-loss) and keeping my hair is important to me :)
Thanks Quantum for your valuable insights. I have not ever taken an anti-depressant, though my psychiatrist had advised me to consider it. I have to so much credit nanna1 stack, after I was in a traumatic car accident, docs told me of expensive reconstructive procedures as the only cure to correct my facial nerve, and yet nanna1's stack strengthened my nerve over a month-usage.
I have a question on what your perspectives are on:
5-HTP vs SSRI's.
I read articles that SSRI's are not as effective as simple 5-Htp 200-300 mg supplements are. But then I also hear that some supplements only act for a short interval and then go dud, whereas prescription meds provide that smooth sustainable coverage.
Last question is tricky: Do you think 400 mg SAM-e (which is very imp to me than any prescribed med), which also increases neurotransmitters necessitate an:
- adjustment of Vyvanse dosage (a dopamine and norapinephrine increaser)
- and should I start on an SSRI for e.g. 50mg, is there an approximate % to adjust SSRI's dosage by.
(I do plan discussing it with doc, but I also know from past experience, they do not take a vitamins serious. Cleveland clinics even laughed at the vitamins I was taking and telling them all about. And well since my Rx meds are optional anyway and I adjust dosage myself sometimes, so its very helpful to know, if there is some approximate formula to take SAM-e into account, because from my personal experience, heck SAM-e is a brilliant healthy vitamin)
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Hey Nanna, Quantum
So I've been lately suffering from fast heartbeat issue. My heartbeat rate is ~120 bpm and yesterday I couldn't even sleep because of it. Until now nothing seems to be wrong with me but I'll be waiting on further tests. The question that I'd like to ask is if the supplements that are mentioned here could cause these issues ? I only take them about 1-2 times a day so I'm not overdosing or anything. And I also finished my GPC so maybe cutting the GPC is causing me this issue ? I'm just checking for the possibility of these stuff because I'm still not sure yet what's causing me this problem.
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Hey Nanna, Quantum
So I've been lately suffering from fast heartbeat issue. My heartbeat rate is ~120 bpm and yesterday I couldn't even sleep because of it. Until now nothing seems to be wrong with me but I'll be waiting on further tests. The question that I'd like to ask is if the supplements that are mentioned here could cause these issues ? I only take them about 1-2 times a day so I'm not overdosing or anything. And I also finished my GPC so maybe cutting the GPC is causing me this issue ? I'm just checking for the possibility of these stuff because I'm still not sure yet what's causing me this problem.
Same here. But about 10-11 years ago when i was generally checkt by an internist, my heartbeat was already to high. He said, nothing serious here but he'd recommend further tests to see why that is. But i didn't go there again.
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Hi Nas, while I am no expert (and dont follow my advice), but logically speaking: Alpha-GPC would if at all decrease your heart-rate and make you feel relaxed (GABA activity) and which is why is great at night too. If you are taking SAM-e, that could potentially stimulate you (and thats why nanna1's post has the comment to not take it at night), and stimulation could increase heart rate, however SAM-e at 400mg the increase should be minimal.
b/w: you guys should post the meds you are taking in your signature line or something. I plan to do it shortly. It will help others too. The reason I say, for e.g. if you were taking a prescription Stimulant, that will definitely increase your heart-rate, and then SAM-e could be potentiating those effects. As always discuss with doc before taking anything - common sense, but still saying.
Hey Nanna, Quantum
So I've been lately suffering from fast heartbeat issue. My heartbeat rate is ~120 bpm and yesterday I couldn't even sleep because of it. Until now nothing seems to be wrong with me but I'll be waiting on further tests. The question that I'd like to ask is if the supplements that are mentioned here could cause these issues ? I only take them about 1-2 times a day so I'm not overdosing or anything. And I also finished my GPC so maybe cutting the GPC is causing me this issue ? I'm just checking for the possibility of these stuff because I'm still not sure yet what's causing me this problem.
Same here. But about 10-11 years ago when i was generally checkt by an internist, my heartbeat was already to high. He said, nothing serious here but he'd recommend further tests to see why that is. But i didn't go there again.
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Hey Nanna, Quantum
So I've been lately suffering from fast heartbeat issue. My heartbeat rate is ~120 bpm and yesterday I couldn't even sleep because of it. Until now nothing seems to be wrong with me but I'll be waiting on further tests. The question that I'd like to ask is if the supplements that are mentioned here could cause these issues ? I only take them about 1-2 times a day so I'm not overdosing or anything. And I also finished my GPC so maybe cutting the GPC is causing me this issue ? I'm just checking for the possibility of these stuff because I'm still not sure yet what's causing me this problem.
You might be developing POTS. My POTS related symptoms exploded years ago from nowhere, I did not take any medicine at all. Observe this behaviour, you may get problems with posturing up and feeling not enough blood is flowing towards your brain. You also may get more sensitive for heat which worsens those symptoms. Buy a heart rate meter and measure the heart rate difference between supine and standing position or measure >120 BPM while standing multiple times when it gets worse and go to your doctor with the data. Send me a PM when POTS symtoms are out of control I can give you some tips.
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Hey Nanna, Quantum
So I've been lately suffering from fast heartbeat issue. My heartbeat rate is ~120 bpm and yesterday I couldn't even sleep because of it. Until now nothing seems to be wrong with me but I'll be waiting on further tests. The question that I'd like to ask is if the supplements that are mentioned here could cause these issues ? I only take them about 1-2 times a day so I'm not overdosing or anything. And I also finished my GPC so maybe cutting the GPC is causing me this issue ? I'm just checking for the possibility of these stuff because I'm still not sure yet what's causing me this problem.
Hi Nas,
Have you checked your blood pressure ? If low, it may be a reflex tachychardia - check with a health professionnal.
Is this fast heart beat constant ? Does it come with nervousness ?
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Hey, Quantum, Muon
So No my blood pressure is fine, and yes it is constant and it doesn't have to do with being nervous.
I did check my heartbeat on my phone and when I am resting and it gets usually normal but when I measure it standing it gets higher; usually above 100, but rarely >120. I think last night when my condition was dire it got there but I'm already taking bisoprolol hemifumarate which is helping a little bit. But will defnetly check on a specialist on the end of this week to see what's wrong.
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Diagnostic Criteria: http://www.dysautonomiainternational.org/page.php?ID=30
There are 2 diagnostic criteria: The increase must be at least >30 BPM or you measure a single value over 120 BPM both within the first 10 minutes of standing in the absense of orthostatic hypotension.
I also recommend getting a reliable upper arm blood pressure+heart rate monitor. This brand is being used in the medical field, the cheap ones are good enough: https://omronhealthcare.com/blood-pressure/
First lay down flat don't elevate your head 45 degrees on a pillow and be sure you are in a resting state. Stand up and measure your blood pressure and heart rate multiple times within and up to 10 minutes of standing. Make sure you don't use interval measurements of less than 2 minutes.
I don't know in which season you are right now but summer could aggrevate these symptoms big time.
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Hi Nas,
From my understanding, heart rate is controlled primarily by three neurotransmitters: epinephrine (adrenaline) (https://en.wikipedia.org/wiki/Epinephrine), norepinephrine (noradrenaline) (https://en.wikipedia.org/wiki/Norepinephrine) and histamine (https://www.britannica.com/science/histamine). These three molecules are fight-or-flight neurotransmitters that can cause short contractions of muscles, increased heart rate and twitching.
- Epinephrine and norepinephrine increase heart rate through the beta1-adrenergic receptor and histamine increases heart rate through the H2 histamine receptor.
- Epinephrine and norepinephrine cause constriction of blood vessels through the alpha1-adrenergic (a1) receptor and histamine constricts blood vessels through the H1 histamine (h1) receptor. Vasoconstriction can cause the heart to have to work harder to pump blood.
Histamine and the heart. Can J Physiol Pharmacol. (1984) (https://www.ncbi.nlm.nih.gov/pubmed/6331617)
The beta1 and H2 receptors are not directly associated with inflammation or the the arachidonic acid cascade.
Alpha1 and H1 receptors are associated with inflammation and arachidonic acid (omega-6) release which I termed POIS Cascade in the original post.
I have not personally noticed an increase in heart rate from taking the supplements in the POIS Cascade stack. That doesn't mean everyone will respond the same way as I have. However, if you are taking prescription medications that affect epinephrine (adrenaline), norepinephrine (noradrenaline) or histamine levels, I recommend making sure there are no drug interactions and/or consulting a physician. I know I over explain sometimes and you may already know most of this, but I hope something here was useful. :)
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Hi nanna1,
My name is Juan Pablo Lewin, from Chile.
I wrote you a PM asking a few things on how to get the stack. Please take a look on your inbox.
Thanks a lot,
JP
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JP, I think that you and I first chatted 10 years ago!
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Hey Nanna
So today I decided that my current method of one time a day is not showing the full potential that I hoped for, and it only seems like I'm always 50% ok. But it is still posing me a number of problems. That's why I'd like to aim higher. Yet the monetary issue is still problematic and the mailing comoany is overpricing anything that I order and I don't think that there are any other companies in my region. So given that, I want to get the full potential of the supplentation without getting myself bankrupt.
You previously mentioned that Sam-e, B6 and lecithin would give me the price's worth. But I still need D3, B1 and Omega 3 for their properties. So what do you suggest ? Something that'll do the trick but at the minimal cost of your original stack ?
Thank you.
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Oh and yes Quantum, I had very low pressure apearently.
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(https://scontent.fsgn5-1.fna.fbcdn.net/v/t1.0-9/24899888_1558431654205646_6274662322307610017_n.jpg?oh=a59dcd71ca3eb0bd20ad53b50dac2f2f&oe=5AC36B90)
I've just started Nanna's stack yesterday. I will report the result here.
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Awesome. I just ordered Nanna's stack as well.
Lately I've had very steady success with my own prepack but the problem remains NE's, and at a young age, because it is such a high risk, my sexual timetable requires really accurate planning... if I don't o after 4 days, the risk is quite high to have a NE, so there is the constant management and worry about this.
I've been taking high doses of fish oil, usually between 3 and 10 capsules a day depending on when I remember. I was wondering, for Nanna and anyone else who takes fish oil, do you eat much fish in your diet? I have basically none. Don't really eat it, except for an occassional side of salmon sushimi. Perhaps I should be taking more fish oil because of this?
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Oh and yes Quantum, I had very low pressure apearently.
Hi Nas, I used to have low pressure ( hypotension) as my main POIS symptom. The most effective way for me to help with this, when I had to work, was to take rosemary and green tea extract, and also, as needed throughout the day, water with salt added to it ( salt causes fluid retention, which makes blood pressure to raise - that's why salt must be avoided by those who have hypertension). Salted water is cheap and very effective. For tolerance, you have to see what one's is able to take. I can take 1/4 teaspoon in a glass of water with no problem. It takes about 20 to 30 mins to show results on the blood monitor. Once my diastolic ( the second, smaller figure) raises at 70 or higher, I feel ok.
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Nanna, for Lecithin my gel cap is 1.2g, is that okay? You put 1.5g. Also, possible to take B1 instead of Benfotiamine?
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Recent treatment strategies with some evidence of efficacy include: alpha-blockers, anti-inflammatory agents, hormonal manipulation, phytotherapy (quercetin, bee pollen), physiotherapy and chronic pain therapy. A stepwise, multimodal approach can be successful for the majority of patients who present with this difficult condition."
I'm testing pollen (2-3 teaspoons 1 hour before orgasm) . I had a good feeling for a first try.
I can't understand why taurine works. There is a legend about taurine in energy drinks and bull semen. Taurine is present in semen too and pollen is semen of flowers. ;D This is not science but somebody gave me pollen and royal gelee so why not try it :)
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Hi all, I'm on day 9 of Nanna's stack and I feel very good, almost no tired after an O (never had this before :o). I wake up with full of energy. My eye's still dry and burning a bit.
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I am happy you found relief to your POIS symptoms, Codeguy.
Keep us informed of how it goes with Nanna's stack.
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Awesome. I just ordered Nanna's stack as well.
Lately I've had very steady success with my own prepack but the problem remains NE's, and at a young age, because it is such a high risk, my sexual timetable requires really accurate planning... if I don't o after 4 days, the risk is quite high to have a NE, so there is the constant management and worry about this.
I've been taking high doses of fish oil, usually between 3 and 10 capsules a day depending on when I remember. I was wondering, for Nanna and anyone else who takes fish oil, do you eat much fish in your diet? I have basically none. Don't really eat it, except for an occassional side of salmon sushimi. Perhaps I should be taking more fish oil because of this?
Hi Michael,
Your comment about NE is a good point. When comparing Nanna's stack to a pre-pack method, a daily dose like Nanna's stack is better when NE are frequent and hard to manage. When NE are less frequent and rarely an issue and health is good when not in POIS, a pre-pack cost less and there is no daily supplementation to take.
In your case, with possible NE every 5 to 7 days, and cause important POIS symptoms, you are better covered with Nanna's daily stack, as long as cost is not an issue on the long run. You are then covered all the time, and not in trouble if having a NE at a totally inappropriate time.
For those on a budget, or for whom NE are less frequent or cause less symptoms than "waking state release", and when releases are quite easy to plan, pre-pack method may be more appropriate ( and pre-pack taken just after NE is still effective to around 50-80%). When I developed my pre-pack method, I had cost-effectiveness in mind, and minimal potential for side effects, and, being in my 50s, NE are not much of an issue now, as long as I have a planned release every 2 to 4 weeks.
What is great, all in all, is that there are more known options now for POIS sufferers to try and get relief for their POIS symptoms ! :) Nanna's stack is a great addition to those potential ways to get relief ( a new POIS sufferer consulting the POIS type chart and search in all forum posts can hope to find something effective for himself).
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Nanna you talked about not being able to source your methylfolate but are you aware there is 200 mcg of folic acid in your NOW branded SAMe supplement?
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Took SAMe this morn, had lower back pain all day... be careful people.
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Took SAMe this morn, had lower back pain all day... be careful people.
I din't experience that, As Nanna warned about Alpha GPC in first page post, may be you should try slowly increasing the dosage.
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Hi Nanna,
I'm planning to start a trial using your stack , but I'm facing difficulties in finding the dosage you have stated.
Can you provide list the product brands you are using ?
ThanX in advance,
Jimmy
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Hi All,
Thanks for your questions:
A list of supplement sources can be found in the The POIS Cascade stack: section of the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). Just click on the supplement name (link) and it will take you to an Amazon.com page for each one.
If you are trying this stack for the first time, I would recommend trying a bundled supplement with SAMe and vitamins B3, B6, B12 like this one Now SAMe 200mg, 60 tablets (enteric coated) (https://www.amazon.com/NOW-SAMe-200-60-Tablets/dp/B0013OW3V6/ref=sr_1_6_s_it?s=hpc&ie=UTF8&qid=1514756760&sr=1-6&keywords=same+200mg). It is easier and more cost effective to try this 4-in-1 pill for the first 30 or more days. If you see results from this, then it may be worth it to get them individually (with the superior form of B3-folate, Metafolin) as listed in the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497).
The amount of vitamin B12 that is listed (50mcg) is a lower limit. You can take up to 1000mcg daily. (see Note: About vitamin B12 (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) section)
Vitamin D3 is only for those who are D3 deficient. I had my D3 checked to know that I needed to take it. If you are not D3 deficient, then this can be eliminated from the stack.
I wish I you all well, and I hope you have a great New Years! :D
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Sorry, I am still confused do you take 1.2g or 2.4g of alpha gpc in a day thanks.
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Big thanks Nanna
Happy new year to you and to everyone !
A question: how many days you recommend I take the stack before I try to orgasm?
And also for alpha-gpc, if it is 2.4g per day, then we should take 8 bills each day? am I correct
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Hey Nanna, Quantum, everybody,
So I've been lately noticing significant hair loss when ever I comb my hair, for the last 3 months or so. Is it possible that some of the supplements within the stack are causing hair fall side effect ?
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Hi Nas,
you could take a look at https://www.mayoclinic.org/diseases-conditions/hair-loss/symptoms-causes/syc-20372926 , there are many possible causes.
Did you have a significant stressing event, 3 to 4 months before this loss had begun?
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No, not a significant one, I don't believe so. But I had about a month of my time when I had a man bun that stretched my hair quite a bit.
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- 4. You are right, in theory drugs that block a1A and h1H should stop POIS. I have not tried any a1A inhibitors, but I have tried h1H inhibitors (Benadryl, Claritin, Allegra) with a lot of success. Benadryl worked the best; no sneezing, runny nose, joint pain or watery eyes. However, Benadryl has a lot of side effects; long-term use is associated with dementia. Claritin and Allegra were okay. Allegra has almost no side effects. But none of the h1H blockers completely got rid of my POIS headaches. Moreover, when I stopped taking the h1H inhibitors there seemed to be a rebound in the receptors. Once the drug wore off, I was even more sensitive to allergens like pollen than before. This ?rebound? happened with all three (Benadryl, Claritin, Allegra). From my experience, unless it addresses a root cause of POIS, a drug (or herb) that solves one problem will inevitably create others. But when you don?t know the root cause and you need short-term relief, definitely try anything that helps.
Hey, Nanna
I personally did not have a success with anti-histamines; my symptoms are mainly cognitive with, a little bit of an inflammation in the urethra (I took anti-histamines before and after orgasm with no apparent success.
I wonder why you did not include a b1 supplement within your stack ? since it plays a major role in blocking H1 ?
Personally trying your stack for four months ( only taking the supplement once a day, but recently I have been trying to take them twice but usually I end up only taking them once because of my busy schedule ) I have notices significant social and cognitive improvement ( be it social more ), but I still suffer significantly on the first and second day of POIS, but after the third day everything almost goes away and I feel like recovery gets faster. So that made me think, why does methyl supplementation works for recovery for me but not when the POIS cascade happen ? ( It does lessen the severity about 30% though ). How long does the cascade last ? does it last for one or two days or is it the after affect inflammation that lasts for that long ?
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Hello, Nana! I'm from the forum http://www.poiscenter.net/. My brothers are for this disease. There Pois 7 people, and they passed tests for hormones. Everyone has a common, this is increased progesterone and cortisol. What do you think about it? Cortisol makes inflammation, its receptors are broken? Through the inflammation, the body gets stressed and in response to stress the body stops working correctly? Thank you! And I think that many of those who took hormonal tests from this forum, were similar. Sorry for the English.
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Hey everyone, so I love the information presented here and I have been trying the recommended supplements, but strangely cold pressed extra virgin olive oil is the only thing that has really given me noticeable relief. But unfortunately it is only temporary (like an hour before I have to drink more olive oil). Does anyone know how DAO factors into this process? I know it?s supposed to help with histamine intolerance. I?m having a hard time making sense of all this, but I feel like for me, doing everything I can to get histamine levels down would help.
Symptoms: constant mouth watering. Muscle twitches all over body. Numb feelings in cheeks and mouth area which leads to severe memory loss, fear, brain fog, social anxiety.
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Hi Nas, vitamin B1 is in the POIS Cascade. Please see the "The POIS Cascade stack: With food, twice daily (fat soluble):" section of the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) for details. I also discuss B1 in the explanation of the POIS Cascade Theory which gives the reason for vitamin B1 in the stack (right below the figure in the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)). If you are not seeing the full relief after the orgasm:
- It might be worth getting your vitamin D3 levels checked and then adjusting the dose accordingly.
- Make sure you take the second dose. You mentioned that sometimes you don't take the second dose. On an orgasm day I always make sure to get the second dose in, because if I miss the 2nd dose then I too would have some lingering symptoms.
- Reducing arachidonic acid (AA) intake is just as important as increasing omega-3 intake. Plants (fruits, vegetables, nuts) don't produce. This means that all your arachidonic acid (AA) is coming from animal fat. Eat leaner cuts of meat or reducing meat consumption are two strategies. Humans don't have a dietary requirement for AA. We can produce all the AA we need from the omega-6, linoleic acid.
Without knowing how you have modified the stack, this is the best answer I can give.
Hi Shep, cortisol and progesterone both use a similar mechanism to work in synergy with vitamin D3 (1,25(OH2)D3) to reduce inflammation [1]. In the figure below vitamin D3 (1,25(OH2)D3) binds to the vitamin D receptor (VDR) and cortisol binds to the glucocorticoid receptor (GCR). Both actions are required for cortisol to have an anti-inflammatory effect. When D3 levels are low cortisol has a pro-inflammatory effect.
(https://i.imgur.com/xXCit9H.jpg)
Figure 1 from [1]: Inhibition of the p38 MAP kinase pathway by 1α,25(OH)2D3 and a mechanism for the synergistic anti-inflammatory effects of 1α,25(OH)2D3 and glucocorticoids. Proinflammatory stimuli lead to p38 MAP kinase phosphorylation and activation which subsequently induces expression of many proinflammatory proteins such as IL-6 and TNFα. Vitamin D3 induces MKP1 expression which dephosphorylates and inactivates p38 MAP kinase. Vitamin D3 stimulates glucocorticoid-induced MKP1 expression via enhanced expression of Med14. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078458/figure/F1/)
When vitamin D levels are low, the body tries to compensate by producing more progesterone levels [2]. So if someone has high cortisol and progesterone levels, this could mean that there is a vitamin D deficiency. Also, if inflammation is high, the body may require more vitamin D3 than the usually daily recommendation. But I think both vitamin D3 and cortisol (or progesterone) are required for the anti-inflammatory effect shown in the above figure.
Vitamin D3 is a strong inhibitor of inflammatory cytokines and NF-kB with an IC50=0.1 uM (roughly 4000 IU per day) [3]. For details about why cytokines, NF-kB and COX-2 are important, see the figure in the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). For information on the IC50 value see Cost effective alternatives for omega-3 (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561)
One last word on vitamin D3. Because of the process depicted in the figure above, it is required for mast cell stabilization [4]. And when there is a vitamin D3 deficiency, mast cells will automatically destablize/degranulate without any external inflammatory stimulus[4].
Hi dwight_schrute, I don't know much about olive oil, but I know it contains COX-1 and COX-2 inhibitors. The figure in the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) explains why I would think a COX-2 inhibitor would be beneficial. You can increase the production of DAO with vitamin C, but I personally haven't found this to be useful.
- Vitamin D in inflammatory diseases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078458/)
- Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885168/)
- Vitamin D Inhibits COX-2 Expression and Inflammatory Response by Targeting Thioesterase Superfamily Member 4 (http://www.jbc.org/content/289/17/11681.long)
- Vitamin D contributes to mast cell stabilization. (https://www.ncbi.nlm.nih.gov/pubmed/27998003)
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Thank you Nana!
There is not an understandable malfunction, the intestine, the sinuses have this inflammation, edema. Perhaps something is not assimilated in the intestine. Or it is a hormonal failure, but it would have turned into a familiar disease for so much time or it is a genetic malfunction in the receptors. I do not know.
I hope that the real cause of the occurrence will be found, and it will be curable!
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I've been tested for IL-6, TNF-alpha and NF-kB multiple times all with normal outcomes.
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Hello Nanna,
Thanks for the reply,
So yeah I did eventually realize that Benfotiamine is b1 because I mainly thought B1 was thaimine, my bad. And btw, Mine has about 250 benfotiamine and only 10mg thiamine.
1- I haven't checked my D3 levels but at the start I did take about 1000IU daily, I'm brown skinned and I live at a scorching hot area so I do assume low levels.
2- I do try to take them on O days but it still does not give full effect, usually I wait the two days period to gain the full effect.
3- I don't usually eat alot of meat, my daily diet is usually heavy on non-meat; I take eggs/cheese and bread with some tea, lunch is usually rice and broth, I don't eat the meat usually and sometimes my broth is purely vegetarian, and dinner is where I either skip it or eat what ever. I'm afraid that my ability to diet is not so good; I don't live in the most economically rich areas in the world and I don't know how to cook anyways so my food supply still comes from my mom's kitchen unfortunately. Yet I do try to eat healthier ( and greasy food make me sick anyways ).
4- I can give you a good example of what I'm currently taking:
Morning: 1- Sam-e 200mg
2- Metafolin 200mg ( even though I'm trying to cut it out currently )
3- b12 50 mcg
4- B6 1/4 of a bite of a 25mg tablet
5- Lecithin 1.5 ( even though I just realized that it is fat soluble )
After meal:
1- Omega 3 ( 1060 EPA & 260 DHA )
2- Benfotiamine 250mg
3- D3 1000IU
5- I also wanted to tell you that I had cut the stack for ~3 days and on Wednesday I was the most energized and social since the entirety of 2017 and cognitively I was much much better. That was very weird for me and that actually made me think about, perhaps cutting the stack usage when I'm 100% ( on the third day ) ? Or it could be just a coincidence, I honestly don't, will be experimenting further.
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Hi Nas,
That's awesome you are seeing results. Keep listening to your body to see what works best for you. I take around 1800mg omega-3 EPA and 2000IU of D3 per day and on orgasms days I usually take 2 x 200mg of SAM-e (400mg). To save money, I have started taking alphaGPC, SAM-e and B1 only on orgasm days. Cutting the stack when you don't need it sounds like a useful strategy to guard against any tolerance that might develop to SAM-e. Thanks for sharing that part ;) . B6 should also help prevent tolerance to SAM-e.
I'm cautious about pausing and resuming omega-3 and D3 since they take days to fully build up in the body. So for me, I always take those two supplements.
In a new development on my side, I have started experimenting with tocotrienols which are rare forms of vitamin E. I did a post about it (http://poiscenter.com/forums/index.php?topic=2597.msg22716#msg22716). It just came in two days ago and subjectively today have noticed more creativity and quickness in my thoughts. And also I feel more resilient to stress. Not much worries me. I'm not entirely sure this is due to the tocotrienols since it has only been two days, but my ultimate goal is to replace/eliminate/reduce the three most expensive parts of the stack (SAM-e/alphaGPC/omega-3). This is not something I would suggest others do. I'm more curious to see if I can reduce the number of pills I take (and save some money).
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I just ordered Nana’s stack. In The Netherlands I can’t buy MuscleTech Omega 4X SX7 Black Onyx 100 softgels. So I have the vitamine D3 and the fish oil sepatertly. I only found fish oil with 504 mg EPA and 378 mg DHA. It’s expensive and a lot of vitamins to take in a day, but let’s give this a try.
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A pill organizers makes it easier.
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certainlypois2, I'm taking two per day. One at breakfast and one at dinner.
what about AGPC is it a total of 1.2g a day or 2.4 g a day.
Hi certainlypois2,
Alpha-GPC is 1.2g per day. 600mg with breakfast and 600mg with dinner. Sorry for the late reply
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certainlypois2, I'm taking two per day. One at breakfast and one at dinner.
what about AGPC is it a total of 1.2g a day or 2.4 g a day.
Hi certainlypois2,
Alpha-GPC is 1.2g per day. 600mg with breakfast and 600mg with dinner. Sorry for the late reply
no problem, this will save me some money
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Hello. In the last week I tried to test each supplement separately, and I came to the conclusion that after taking Benfotiamine (Doctor best), which contains 150 mg of benfotiamine and 12 mg of l-leucine, I feel heartache, severe anxiety and a little fatigue. Could this be because of leucine? (I read in the early post of Quantum that BCAA competes with tryptophan, and tryptophan is very necessary)
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Hello. In the last week I tried to test each supplement separately, and I came to the conclusion that after taking Benfotiamine (Doctor best), which contains 150 mg of benfotiamine and 12 mg of l-leucine, I feel heartache, severe anxiety and a little fatigue. Could this be because of leucine? (I read in the early post of Quantum that BCAA competes with tryptophan, and tryptophan is very necessary)
Hi Rinat,
Tryprophan and Leucine, as well as isoleucine and Valine, use the same transporter, LAT1, in order to cross the blood-brain barrier ( BBB) and get into the brain. If there is a surge of leucine in the blood, there will be less place left on the "ferry" for tryptophan (Trp) to make it into the brain. But, in order to be transformed in serotonin, tryptophan must cross into the brain. If Trp is prevented to make it into the brain, less serotonin is produced. This can have an effect on mood and raise anxiety ( for those who would like a more in-depth explanation, see http://poiscenter.com/forums/index.php?topic=1565.msg14730#msg14730 and http://poiscenter.com/forums/index.php?topic=1235.msg15588#msg15588 )
However, 12 mg of leucine does not sound like a high dose, as daily requirements are said to be around 34 mg per day for an adult ( https://www.webmd.com/vitamins-supplements/ingredientmono-1005-branched-chain%20amino%20acids.aspx?activeingredientid=1005&activeingredientname=branched-chain%20amino%20acids ) . To be sure that these side effects you have are linked to the leucine, you should try to find a Benfotiamine supplement that does not contain leucine, and see if it also cause this side effect for you. For someone very vulnerable to this effect, a small does could be enough to cause problems.
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1.thanks for your answer, Quantum.:) I used to take benfotiamine with thiamine, and there were no such symptoms. In addition, another symptom was pain in the upper back, around the neck. But gradually the symptoms go away. The main symptom is pain in the heart, a quick pulse, it scares me, because I think it's dangerous.
2.I feel good after Sam (good brain work and good mood) .I take it while in a day (so that there is no overdose). But I took it in the evening on the same day with benfotiaminom (Maybe it influenced).The first time I took it without vitamins b, and felt fragility in the bones. But then with vitamin b it was better.
3. Also, omega-3 is good for me. My acne almost go away with it, and better mood. But it's expensive for me, so I stopped taking it.
4.Tmg seemed first good for me. (better ability to talk) But then there was pain in the bones, dull hair and weight loss.
5. I still take Vitamin d3, it seems good :)
What can you advise from acne?) ???
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Will vitamin E help with acne?(if omega helped)?
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Hello everyone, very interested to know what works for others here am going to read through here. I try various vitamins to treat my pois, going to list below as you may can tell me what may causing me issue. Recently I notice my face puffing up, skin on cheeks hardening up, and just something inside trapped within skin and surface showing some uneven patches. Like even when I move my fingers across face I can tell there is even different sensation to skin and it feels wood like, though wife says it not too obvious. Yesterday I stop L-Citrulline to see if it may be causing it though still cannot figure out. You think my current symptom is allergy?
Benfotiamine 150mg, Alpha Lipoic Acid 300mg, Asgwaghandha Root powder 1200mg with 5mg Black Pepper, L-Citrulline 750mg, L-Lysine 500mg
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Will vitamin E help with acne?(if omega helped)?
I don’t think mature POIS-patients have acne. I think we have Pityrosporum folliculitis. Chevk this topic:
http://poiscenter.com/forums/index.php?topic=2612.msg22755#msg22755
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Hello everyone, very interested to know what works for others here am going to read through here. I try various vitamins to treat my pois, going to list below as you may can tell me what may causing me issue. Recently I notice my face puffing up, skin on cheeks hardening up, and just something inside trapped within skin and surface showing some uneven patches. Like even when I move my fingers across face I can tell there is even different sensation to skin and it feels wood like, though wife says it not too obvious. Yesterday I stop L-Citrulline to see if it may be causing it though still cannot figure out. You think my current symptom is allergy?
Benfotiamine 150mg, Alpha Lipoic Acid 300mg, Asgwaghandha Root powder 1200mg with 5mg Black Pepper, L-Citrulline 750mg, L-Lysine 500mg
Hi Swell, and welcome on the forum.
I cannot tell which one of your supplements is causing this skin reaction, but if try to eliminate them one at a time, you should be able to identify which one is the culprit.
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Hi, swell, welcome to POISCenter!
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Hi all!
Yesterday I tried to use SAM-e and vitamins b. In general, the condition was good, but there was a pain in the heart. Then I decided to use TMG, and it seems the pain is gone. Today I again used vitamin B, only without SAM-e, in the morning I still felt a pain in my heart, I again took 500 mg of TMG and it seems better :) Now I plan to take bi-daily SAM-E(200 vu), every day vitamin B (3 mg b6, 2.5 mg thiamine, 4.5 mg b12, 300 mg glycine), and TMG (500 mg).(Also vitamin D3 and omega-3, (EPA-250 mg,because it's expensive:)).
. I plan to use Quantum's pre-pack befor the O.. I also limit sugar.
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Will vitamin E help with acne?(if omega helped)?
I don’t think mature POIS-patients have acne. I think we have Pityrosporum folliculitis. Chevk this topic:
http://poiscenter.com/forums/index.php?topic=2612.msg22755#msg22755
As you mentioned in the other post, Pityrosporum folliculitis can be treated with Nizoral Shampoo.
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Thank you quantum. I stopped L-cit and Asgwagh. and think now swelling to be gone. Will soon re add Asgwagh. to see if it was L-cit for my trouble as I suspect that to be.
Hello everyone, very interested to know what works for others here am going to read through here. I try various vitamins to treat my pois, going to list below as you may can tell me what may causing me issue. Recently I notice my face puffing up, skin on cheeks hardening up, and just something inside trapped within skin and surface showing some uneven patches. Like even when I move my fingers across face I can tell there is even different sensation to skin and it feels wood like, though wife says it not too obvious. Yesterday I stop L-Citrulline to see if it may be causing it though still cannot figure out. You think my current symptom is allergy?
Benfotiamine 150mg, Alpha Lipoic Acid 300mg, Asgwaghandha Root powder 1200mg with 5mg Black Pepper, L-Citrulline 750mg, L-Lysine 500mg
Hi Swell, and welcome on the forum.
I cannot tell which one of your supplements is causing this skin reaction, but if try to eliminate them one at a time, you should be able to identify which one is the culprit.
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Thank you demografx. Lots good material here.
Hi, swell, welcome to POISCenter!
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This post is about theory. Below is a diagram showing the central role that NF-kB (NF-kappaBeta) (https://en.wikipedia.org/wiki/NF-%CE%BAB) plays in inflammation. Don't worry about trying to understand all the complicated arrows.
- Region 1 (above the top dashed-line) shows initiators of inflammation (TNF, IL-1, bacterial antigen, virus, etc...).
- Region 2 (below the top dashed-line) shows the NF-kB activator (IKK-alpha, IKK-beta, IKK-gamma) (https://i.imgur.com/aiR0gIR.jpg) (3 red rectangles).
- Region 3 shows a bunch of biochemistry with activated NF-kB.
- Region 4 (below the bottom dotted-line) shows the genetic up-regulation of Oxidative enzymes (COX, LOX, TDO, IDO, KMO, iNOS, etc...) by NF-kB.
Oxidative enzymes are responsible for inflammation (oxidative stress, allergy, depression, DNA damage, asthma, aging, and other inflammatory diseases). The oxidative enzymes are not shown in the below image.
(https://i.imgur.com/zQkZPNM.jpg)
In the above diagram (Region 1), IL-1 is just representative of the inflammatory class of cytokines (IL-6, IL-8, etc...). All of the inflammatory cytokines activate NF-kB. The anti-inflammatory cytokines (i.e. IL-10) inhibit NF-kB. This discussion fits into the POIS Cascade model in the following way:
(https://i.imgur.com/5vYbemZ.gif)
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Hi Nanna,
Oregano, Coffee, Thyme, Clove, and Walnuts seems to Inhibit NF-?B , at cellular level ( ref: http://cancerpreventionresearch.aacrjournals.org/content/3/5/653 )
However, it is not clear how using these would translate in term of POIS symptoms relief.
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Nanna's stack did not seem to help me... I upped my fish oil dosage to about 10 capsules a day for over a month. (EPA 1800 mg total). SAMe. B1 (Bennfetiomine), Vitamin b's. Lecithin. Etc.
The first week using SAMe my POIS was a bit worse... oh well. :) Nice try.
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Hi Nanna,
I asked a doctor here to translate the medicines you mentioned to a prescription and below is what I got. Do you think below will give desired result
https://www.1mg.com/otc/shelcal-500-tablet-otc137210
https://www.1mg.com/otc/tetrafol-plus-tablet-otc149386
https://www.1mg.com/otc/multivite-fm-omega-capsule-otc67645
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Hi Michael
For me, I have not committed high doses like two pills a day. But I can tell you that the pills worked as symptoms reducers rather than POIS preventers. Which is kinda disappointing given the heavy price we pay. And it also proves that no one have yet to find a universal solution.
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Nanna's stack did not seem to help me... I upped my fish oil dosage to about 10 capsules a day for over a month. (EPA 1800 mg total). SAMe. B1 (Bennfetiomine), Vitamin b's. Lecithin. Etc.
The first week using SAMe my POIS was a bit worse... oh well. :) Nice try.
So untill now Nanna is the only one who finds relief from Nanna’s stack? I bought all the medicines, but first I want to empty my taurine bottle. Because of an attack on my immune system I was too sick to have sexual activity, so I didn’t find out if taurine helps me. If not, I will try Nanna’s stack about a few weeks.
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Nope, Nanna's stack didn't seem to help at all in my case. Everyone's body and diet differ and this makes a huge difference. I believe this forum is helpful in the sense that everybody lists what helps them personally and so it leaves you in a position to try every single option and see what works for you...
There are ingredients within Nanna's stack that I am sure reduce my POIS significantly, being Vitamin B6, B1 and 12. It seems to me that most people are benefiting from high dose Vitamin B's.
Even Quantum, who does not include vitamin B's in his prepack, mentioned that Vitamin Bs helped reduce his POIS greatly from memory - correct me if wrong Q. So it seems that there are certain ingredients that are more universally helpful than others. I have no idea if fish oil is helping at all... anyway I don't eat fish so I take them happily for the omega 3. The first time I got nearly full relief from POIS I had not taken any fish oil on a daily basis, I only took it the once with prepack. So I have no idea what role if any that plays for me personally.
Quantum's prepack didn't work for me. Nanna's didn't. Yet all of us somehow benefit from Vitamin B's...
Not sure if I have any point at all or am just rambling on...
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Hi Michael218. For me taking only 200mg SAMe lead me in horible state.
That mean this is not for me.
B vit not helping me at all, but I didnt try active b vitamines because cant get them in my country. I am ordered them to test because( kurtosis teory of genetics mutations).
My main problem is evan in apstineting period NERVE OVERSENSIBILITY, that mening evan touching and masaging lover back erea (wright up prostate erea) couse me heatrt palpilation, pelvis floar muscule cramps , asopagus muscule cramps... that afect my quality of life a lot(sewere breathing probl). This all X10 after eyaculation I barly surwive.
When I eksplane this to eny doctor, nowbody bolive me.
Only thing that help me to save my life in hard atacs are small dose of benzos.
All that lead me to i myabe hawe STIFF MAN SINDROME because good reaction on bezos. Stress and wory are bigg NO to our condition, bat that for me is imposible to manage, because i must earn mony for living.
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Even Quantum, who does not include vitamin B's in his prepack, mentioned that Vitamin Bs helped reduce his POIS greatly from memory - correct me if wrong Q. So it seems that there are certain ingredients that are more universally helpful than others.
....
Quantum's prepack didn't work for me. Nanna's didn't. Yet all of us somehow benefit from Vitamin B's...
Hi Michael,
I do not use B complex very often, but they are good for my energy level, if I do not take them on a regular basis. Otherwise, the effect fades after a week or so. I cannot comment about memory problems, since POIS does not cause me memory problems, or other cognitive problem ( but a lot of emotional problems, as well as extreme fatigue, and hypotension).
For about 2 to 3 months, you had great results with you modified pre-pack version, last year. I have even included you in my POIS chart as reference member in the type responding to pre-pack ( around 2017-07, see http://poiscenter.com/forums/index.php?topic=2338.msg21433#msg21433). Does it mean that, sadly, you no longer have symptoms reduction with your personal pre-pack? Or that % of relief is not at 70 anymore? If so, anything special happened, or it just slowly has lost its effectiveness ?
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Hi there. Quantum, i recall you writing that B vitamins reduced your POIS a lot before you came up with your own prepack.
Fortunately my "prepack" is still very effective. It varies. But usually about 70% effective which is a huge leap. Crucially, my POIS used to be 2 days of hell. The second day was the worst. Absolute hell. Now, I basically have no second day of POIS. So there is a significant reduction on the first day, and I can count on second day being relatively normal and not distuptive to life. Huge leap.
HOPEONEDAY, it is important to mention, B vitamins only appear to be effective IF YOU TAKE THEM IRREGULARLY, NOT EVERY DAY. I wrote that in caps to stress this point. From what I conclude based on other users experience and my own, B vitamins become useless if you use them every day. No idea why, I guess immunity builds up.
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Nana stack is interesting. Many a vitamin are used in chronic fatigue syndrome. Sam-e is excitory med it is not good for everyone if you have nerve overactivity or sensitivity. I like Sam-e I need to begin again it takes fog away for me and make me happy. BetaBlocker is good for you it is opposite to SAM. Sam-e calms you but excite you, BetaBlocker calms you but do not energy you.
Hi Michael218. For me taking only 200mg SAMe lead me in horible state.
That mean this is not for me.
B vit not helping me at all, but I didnt try active b vitamines because cant get them in my country. I am ordered them to test because( kurtosis teory of genetics mutations).
My main problem is evan in apstineting period NERVE OVERSENSIBILITY, that mening evan touching and masaging lover back erea (wright up prostate erea) couse me heatrt palpilation, pelvis floar muscule cramps , asopagus muscule cramps... that afect my quality of life a lot(sewere breathing probl). This all X10 after eyaculation I barly surwive.
When I eksplane this to eny doctor, nowbody bolive me.
Only thing that help me to save my life in hard atacs are small dose of benzos.
All that lead me to i myabe hawe STIFF MAN SINDROME because good reaction on bezos. Stress and wory are bigg NO to our condition, bat that for me is imposible to manage, because i must earn mony for living.
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Nana1 I have inflammation visible in skin. Your stack takes on neurology or brain symptom good only?. So far what help me little is Progesterone, Niacin for inflammation in skin. Sam-e in past help me very good on mood and mental things.
The theory diagram below show the COX2, 5LOX and inflamation mediators but not inflamation sensors the Mastcell and Macrophages. Where do they fit in diagram? or is it a separate pathway.
This post is about theory. Below is a diagram showing the central role that NF-kB (NF-kappaBeta) (https://en.wikipedia.org/wiki/NF-%CE%BAB) plays in inflammation. Don't worry about trying to understand all the complicated arrows.
- Region 1 (above the top dashed-line) shows initiators of inflammation (TNF, IL-1, bacterial antigen, virus, etc...).
- Region 2 (below the top dashed-line) shows the NF-kB activator (IKK-alpha, IKK-beta, IKK-gamma) (https://i.imgur.com/aiR0gIR.jpg) (3 red rectangles).
- Region 3 shows a bunch of biochemistry with activated NF-kB.
- Region 4 (below the bottom dotted-line) shows the genetic up-regulation of Oxidative enzymes (COX, LOX, TDO, IDO, KMO, iNOS, etc...) by NF-kB.
Oxidative enzymes are responsible for inflammation (oxidative stress, allergy, depression, DNA damage, asthma, aging, and other inflammatory diseases). The oxidative enzymes are not shown in the below image.
(https://i.imgur.com/zQkZPNM.jpg)
In the above diagram (Region 1), IL-1 is just representative of the inflammatory class of cytokines (IL-6, IL-8, etc...). All of the inflammatory cytokines activate NF-kB. The anti-inflammatory cytokines (i.e. IL-10) inhibit NF-kB. This discussion fits into the POIS Cascade model in the following way:
(https://i.imgur.com/5vYbemZ.gif)
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Hi swell,
Immune cells (mast cell, white blood cell, etc...seen in the below diagram) strongly express NF-kB when activated (click the picture to expand it):
(https://upload.wikimedia.org/wikipedia/commons/thumb/f/f0/Hematopoiesis_simple.svg/1280px-Hematopoiesis_simple.svg.png)
Therefore, the diagram that I posted on Feb. 4, 2018 (NF-kB Signaling (https://i.imgur.com/zQkZPNM.jpg)) can be viewed as showing the inside of an immune cell. The outer surface of the cell with its receptors is shown in Region 1. However, almost all cell types express NF-kB to some degree. So immune cells like mast cells and macrophages may not be the only cells involved in COX-2/5-LOX up-regulation.
Hi rakeshbaasu,
I noticed that your vitamin D3 supplement contains extra calcium. I would avoid supplementing calcium since free calcium ions in the blood can increase the release of arachidonic acid. Also, I didn't see a source of methyl groups (choline or betaine, etc...) or SAM-e in your stack. If you are having trouble finding all the methylation supplements, you may consider B complex since B complex usually contains some choline. However, be careful to monitor your daily B6 dosage (see original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)).
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In the thread "Muon's Case (http://poiscenter.com/forums/index.php?topic=2545.0)", one of the POIS Center members generously shared his blood test results showing elevated levels of human herpesvirus type 3 (https://en.wikipedia.org/wiki/Varicella_zoster_virus) (HHV-3, Varicella zoster virus, chickenpox) and human herpesvirus 5 (HHV-5, cytomegalovirus). HHV-5 doesn't seem to be POIS related because it is very common and has few symptoms. However, HHV-3 has symptoms that are very similar to POIS. I also was infected with HHV-3 as a child. So, I did some reading recently on herpes viruses (herpes simplex virus, HSV) and (human herpesvirus, HHV) and just wanted to share. I assume the herpes HHV-(1,2,3,4,5,6) have similar in basic structure/function. HSV-1 and HSV-2 are also known as HHV-1 and HHV-2 respectively. So I referred to HHV and HSV interchangeably.
HHV-3 infects and is stored in cells of the nervous system (neurons, astrocytes, etc...). Once herpes is activated, it starts to replicate and migrate through the nervous system in the dendrites. In these cells, HSV upregulates COX-2 in order to replicate [A1,A2,A3]. The upregulation of COX-2 by HSV occurs through JNK gene activation [J1,J2,J3]. HSV activation requires both JNK up-regulation and de-methylation of the herpes DNA [J2,J3]. The authors of this paper were able to stop herpes outbreaks by inhibiting the JNK gene alone [J1,J3]. I tried to summarize my current understanding of the papers [A1,A2,A3,J1,J2,J3] in the below diagram:
(https://i.imgur.com/GK8pPvh.png)
Prostaglandins (https://en.wikipedia.org/wiki/Prostaglandin) activate JNK. JNK de-methylates viral DNA leading to viral symptoms. JNK also up-regulates COX-2 to produce more prostaglandins. This cycle requires a steady supply of arachidonic acid (https://en.wikipedia.org/wiki/Arachidonic_acid). (This diagram is greatly simplified. For example, PGE2 upregulates IFN-y/TDO/IDO, but that is not shown here.)
Natural JNK inhibitors:
Taurine:
During inflammation, taurine is converted into the anti-inflammatory molecule, Taurine chloramine (N-Chlorotaurine), inside of activated immune cells (neutrophil, macrophage, mast cells, etc...) (https://upload.wikimedia.org/wikipedia/commons/f/f0/Hematopoiesis_simple.svg)[D1]. Taurine chloramine then selectively inhibits inflammatory enzymes such as COX-2 [E] and 5-LOX [F]. Taurine has been shown to inhibit HSV in vitro in human cells [K4] and inhibit JNK activation in vivo[K1,K2,K3] in animals.
PQQ:
Pyrroloquinoline Quinone (PQQ) downregulates every known inflammatory pathway, including JNK, NF-kB, COX-2 and several cytokines [L1,L2]. However, PQQ is believed to have poor bioavailability. So it is not clear how much is actually absorbed in the body. Possible source (https://www.amazon.com/Jarrow-Formulas-Ubiquinol-Pyrroloquinoline-Cognitive/dp/B00CP8T8FI/ref=sr_1_1_a_it?ie=UTF8&qid=1520803584&sr=8-1&keywords=ActivePQQ&th=1)
Methylators:
The HSV virus replicates in a low methylation environment. There is already plenty of discussion of methyl donors in this thread. So I'll just refer to the below diagram. Purple arrows inserted by me:
(1)SAMe, (2)TMG (betaine) or choline, (3)B12, (4)B6, (5)B9 (metafolin)
(http://i.imgur.com/hq96vF1.jpg)
COX-2 inhibitors:
My neurologist once prescribed the COX-2 inhibitor, indomethacin, to me to treat orgasm induced headaches. I didn't take it at the time because indomethacin has longterm side effects on the stomach and liver. Recently, I tested indomethacin (~30 min prior to sex) without taking the POIS Cascade Stack for one-week. Indomethacin alone stopped 85% of my POIS symptoms. Their was some mild discomfort in my left ear and left side of forehead. This discomfort did not effect my productivity at work. I took a second dose of indomethacin the next day along with a Gen-1 H1-histamine receptor blocker, and all of my POIS symptoms were gone.
Gallic acid:
Because of the side-effects of indomethacin, I find it unexceptable as a longterm treatment. One alternative could be Gallic acid. Gallic acid is a 10 times stronger COX-2 inhibitor than indomethacin, and it is also a strong mast cell stabilizer [G1]. Gallic acid is a moderate herpes simplex virus (HSV) inhibitor [H1,H2] although the anti-viral medicine Acyclovir was 100 times more effective than Gallic acid [H1]. Gallic acid is found in tea leaves, cocao and apple cider vinegar. More info here. (https://poiscenter.com/forums/index.php?topic=2597.msg23199#msg23199)
I don't know if a herpes is a cause of POIS, but it seems interesting. Muon's blood test results also showed a possible candida infection. So there could be other infections. I hope this sparks some discussion and ideas of a cause.
References:
A1. Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion. (https://www.ncbi.nlm.nih.gov/pubmed/20169190)
A2. COX-2 Induction during Murine Gammaherpesvirus 68 Infection Leads to Enhancement of Viral Gene Expression (http://jvi.asm.org/content/77/23/12753.full)
A3. Cyclooxygenase-1 and -2 Are Required for Production of Infectious Pseudorabies Virus (http://jvi.asm.org/content/78/23/12964.full)
A4. Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human Herpesvirus 6: ROLE FOR CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN AND ACTIVATOR PROTEIN-1 (http://www.jbc.org/content/277/34/30665.full?utm_source=TrendMD&utm_medium=cpc&utm_campaign=Journal_of_Biological_Chemistry_TrendMD_0)
D1. Taurine chloramine (https://www.ncbi.nlm.nih.gov/pubmed/23933994)
E. Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. (https://www.ncbi.nlm.nih.gov/pubmed/12794822)
F. Influence of taurine and a substituted taurine on the respiratory burst pathway in the inflammatory response (https://pdfs.semanticscholar.org/d826/55ec421ea8073b85b7c4b2f4137c956ccd10.pdf)
G. Cost effective alternatives for omega-3: Gallic acid (https://poiscenter.com/forums/index.php?topic=2597.msg23199#msg23199)
H1. Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate (http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762008000500005&lng=en&nrm=iso&tlng=en)
H2. Evaluation of Anti-HSV-2 Activity of Gallic Acid and Pentyl Gallate (https://www.jstage.jst.go.jp/article/bpb/31/5/31_5_903/_article)
I1. Effects of caffeine and paracetamol alone or in combination with acetylsalicylic acid on prostaglandin E2 synthesis in rat microglial cells (https://www.sciencedirect.com/science/article/pii/S0028390800000459?via%3Dihub)
I2. Caffeine Promotes Ultraviolet B-induced Apoptosis in Human Keratinocytes without Complete DNA Repair (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123050/)
J1. Discovery shows how herpes simplex virus reactivates in neurons to trigger disease (https://www.sciencedaily.com/releases/2015/12/151209143105.htm)
J2. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease (http://www.pnas.org/content/101/2/665)
J3. Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681005/)
K1. Taurine Protects Mouse Liver Against Arsenic-Induced Apoptosis Through JNK Pathway. (https://www.ncbi.nlm.nih.gov/pubmed/28849505)
K2. Taurine reduces FK506-induced generation of ROS and activation of JNK and Bax in Madin Darby canine kidney cells. (https://www.ncbi.nlm.nih.gov/pubmed/20056734)
K3. Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK (https://www.sciencedirect.com/science/article/abs/pii/S0006295211000657)
K4. Activity of N-chlorotaurine against herpes simplex- and adenoviruses. (https://www.ncbi.nlm.nih.gov/pubmed/9614001)
L1. Pyrroloquinoline Quinone (PQQ) Inhibits Lipopolysaccharide Induced Inflammation in Part via Downregulated NF-κB and p38/JNK Activation in Microglial and Attenuates Microglia Activation in Lipopolysaccharide Treatment Mice (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196908/)
L2. Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways. (https://www.ncbi.nlm.nih.gov/pubmed/26319019)
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Nana you might be reading my posts about hhv- http://poiscenter.com/forums/index.php?topic=2584.msg23205#msg23205
In those links resarch are discovered that hhv is inwolved ewan in undermetalation if i read corect.
Guys, lets chouse 2-3 poisers who are in usa, germany ...etc, i mean from countres who hawe ability to make prc dna virus tests and most adwanced tests.
Test from blod (they say) is only maybe relevant if infection is right now.
Nana, is Moun hawe elevated hhv 3 in pois or?
Conection -The girl name AJS (I put here girl on perpos) from naked forum say that only thing she kows is that her pois started after geting shingles.
And she say, that they found hi elevated levels of antibodies 3 diferent viruses.
lets check is there eny virus in our nerves, hhv6(this virus could be in our dna, geneticly) etc...
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Hi Hopeoneday,
Your post seems very relevant to this discussion. You are already ahead of me with some of this information. I didn't know about the vagus nerve infection hypothesis (http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis), but the link that you posted in (http://poiscenter.com/forums/index.php?topic=2584.msg23205#msg23205) is very informative. I will keep reading up on this. Thanks! :D
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Hey Nanna,
To my understanding HHV-3 is basically VZV virus, which is chickenpox. Chickenpox in later stages does go dormant in the nerves. So in the case of Muon, did he experience chickenpox symptoms when he was a kid? Also aren't most of people around the developed world have chickenpox vaccinated ? I know I did personally.
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Hi Nas,
You are correct that human herpes virus-3 (HHV-3) is VZV, chickenpox, shingles. The HHV-3 vaccine is a live virus that has been weakened. But in some people, the vaccine can still infect the nervous system if the immune system does not eliminate it fast enough.
Regarding herpes zoster, the US Centers for Disease Control states: "Chickenpox vaccines contain weakened live VZV, which may cause latent (dormant) infection. The vaccine-strain VZV can reactivate later in life and cause shingles. However, the risk of getting shingles from vaccine-strain VZV after chickenpox vaccination is much lower than getting shingles after natural infection with wild-type VZV." (https://en.wikipedia.org/wiki/Varicella_vaccine#Herpes_zoster)
"Vaccines are less effective among high-risk patients, as well as being more dangerous because they contain attenuated live virus. In a study performed on children with an impaired immune system, 30% had lost the antibody after five years, and 8% had already caught wild chickenpox in that five-year period." (https://en.wikipedia.org/wiki/Varicella_vaccine#Chickenpox)
I don't know if Muon was infected with HHV-3 as a child, but his virus test shows a HHV-3 (varicella-zoster) and HHV-5 (cytomegalovirus) infection. (https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+4-3+LTT+Herpes+14-08-2015.pdf) He does not have a HHV-6 infection. So if herpes is involved with POIS, HHV-6 is not required. But it could also be the case that different types of POIS come from different HHV viruses.
Herpes viruses are not permanently latent (dormant). For HHV-1 and HHV-2, it was shown that stress (through JNK) triggers the activation of those viruses [J1,J3]. The shingles disease occurs when HHV-3 is reactivated when the immune system is compromised and can't fight it off. As long as the immune system is strong, the HHV can only dwell and spread through the nervous system in the neurons (and similar cells). It is very difficult for an immune cell to kill a neuron, because that would destroy memory. So HHV can hide in neurons. When a HHV tries to leave the nervous system it gets attacked and killed by immune cells. The immune system attack on the spreading HHV-3 is what may be causing POIS symptoms. That is the mechanism pictured below:
(https://i.imgur.com/GK8pPvh.png)
Prostaglandins activate JNK. JNK de-methylates viral DNA leading to viral symptoms. JNK also up-regulates COX-2 to produce more prostaglandins. This cycle requires a steady supply of arachidonic acid. (This diagram is greatly simplified. For example, PGE2 upregulates IFN-y/TDO/IDO, but that is not shown here.) (http://poiscenter.com/forums/index.php?topic=2502.msg23222#msg23222)
I obviously don't know anything for sure. But I thought it might be helpful to discuss the idea of an HHV infection.
Press release:
J1. Discovery shows how herpes simplex virus reactivates in neurons to trigger disease (https://www.sciencedaily.com/releases/2015/12/151209143105.htm)
Original research paper:
J3. Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681005/)
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Ok, so how does that possibly relate to POIS? How does an orgasm/ejaculation affect the HHV-3 trigger mechanics? I.e. how does stress trigger correlate with ejaculation? Also if that was the case, shouldn't we be having shingles when the Herpes start replicating?
I feel the infection theory could be a good one since I've always suffered from an inflamed urethra during POIS ( even inflamed anus but I don't know if that correlates ). The human body is a very complicated system you never know what can cause what.
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Hi Nas,
Thanks for the interesting questions/comments. The shingles outbreak only occurs when the immune system is weak and cannot fight off the spread of the virus. The virus-POIS mechanism that I discussed earlier (March 11 (https://poiscenter.com/forums/index.php?topic=2502.msg23222#msg23222), March 12 (https://poiscenter.com/forums/index.php?topic=2502.msg23228#msg23228)) assumes that the immune system is functioning properly. The virus is typically latent (dormant) within neurons and nervous system related cells. Once the stress trigger activates the virus, the virus spreads and causes the immune system to respond.
- Newly infected cells upregulate 5-LOX, IFN-gamma and other proteins to tell the immune system (T-cells, mast cells, white blood cells, etc...) where the virus is located.
- The immune cells attack the virus-infected cells with inflammation through neurotransmitters (histamine), cytokines (IL-8), and free radicals (hydrogen peroxide, nitric oxide).
- The inflammation kills the infected cells and the virus.
- The dead cells and viruses are "eaten" and cleared from the body (allergy).
In the case of HHV-3, this attack on the virus would prevent a shingles outbreak by killing off the virus whenever it tries to escape the nervous system. Unfortunately, the attack (inflammation) and clearance (allergy) by the immune system of the pathogen (virus) can also make people feel very sick.
As for the stress trigger that activates JNK and herpes (https://www.sciencedaily.com/releases/2015/12/151209143105.htm), I don't know for sure since I am still learning about JNK. But I think there are three likely candidates:
1. The breakdown of cyclic AMP by PDE4 (http://www.discoverpde4.com/).
2. A rise in cyclic GMP by NO production.
3. Increased PGE2 (prostaglandin).
cAMP and cGMP are both involved in penile erections. cGMP in the penis creates the erection, but it can also stimulate JNK and herpes replication. cAMP inhibits JNK and herpes replication.
PGE2 is produced whenever semen is produced and is usually found in high concentrations in the semen of healthy people. PGE2 activates JNK. The word prostaglandin comes from two root words, prostate gland. It comes from arachidonic acid interacting with the COX-2 enzyme.
Since COX-2 inhibitors (indomethacin) and PDE4 inhibitors (quercetin and curcumin) reduce POIS symptoms, the trigger could be a combination of 1. and 3. All of these molecules (cAMP, cGMP, PGE2) are short ranged, meaning they don't travel very far from where they are created before being broken down. There are other stress related molecules that can trigger JNK, but that's all I know about stress triggers right now. I'm still reading about the potential virus-POIS link.
Thanks again Nas. :)
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Yes I had chickenpox as a kid. Stress can trigger an attack of flares throughout my body in alternating fashion, taking turns. When one flare which takes a few seconds or less in duration fades out another one pops up somewhere else, it's like the body and something else playing a game of whack-a-mole where the body is one step behind. (mast cell attack, virus, cytokine release???)
So a virus can replicate itself without the body producing specific IgM? IgM has a relatively high half life. You may ask yourself if IFN-g is elevated in my case to suppress an infection. Also desenz treatment is able to reverse polarization from Th2 to Th1 in general. I suspect PGD2 acts on the CRTH2 of Th2 cells which decreases interferon gamma after orgasm and the body elevates IgG4 to dampen this Th2 response. My brother has POIS but doesn't have his IFN-g elevated, maybe this is potential latent infection which acts parallel next to POIS.
Maybe worth mentioning, I have used liquid H2O2 in the past (motivation was candida albicans). This improved a lot of symptoms in general but had not any influence on POIS. It only worked with water (250-300 ml water). IL-8 was tested positive 10 out of 10 times if you sum up the IL-8 tests of me and my brother. Perhaps this is a potential target for POIS research. If a majority of patients are postive for this parameter you can associate it with POIS, then we have something coupled to POIS, now we have nothing.
I'm in a proces getting these done: https://www.mastcellaction.org/assets/file?filePath=__/mast-cell-activation-markers-final-flyer.pdf
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Very interesting Nanna. So is it possible to treat HHV-3 when it's dormant I wonder?
I would also like to note since HHV-3 is a herpes virus, unsanitary masturbation ( since I'm a virgin ) could be possibly the place of infection for many of us. And I'm not sure about my urethra inflammation but its correlation with ejaculation makes me even a bigger believer of the viral theory. Will like to see further tests from Muon and other POISers in the future.
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Hi Muon,
Thank you for sharing your personal experience and test results. I plan to get some detailed test results soon, but as you probably know these virus test are expensive. I agree with you that prostaglandins could be involved in how the immune system responds after orgasm since many POIS stacks seem to affect the arachidonic acid cascade. Your idea about PGD2 and IFN-gamma is interesting especially considering your brother doesn't have elevated IFN-gamma. This information will help narrow down which test I need (or don't need to get).
I express caution about using IgM test to determine herpes virus reactivation/replication. The herpes virus can replicate without the body producing IgM. In people with active shingles outbreak, it may be more common to have a negative IgM test than a positive one:
"IgM testing is considerably less sensitive than PCR testing of skin lesions. Commercial IgM assay may not be reliable and false negative IgM results are not uncommon." Center for Disease Control: Chickenpox (Varicella): Interpretation of Laboratory Tests for VZV: Laboratory Confirmation of Suspected Varicella (https://www.cdc.gov/chickenpox/hcp/lab-tests.html)
"Serum specimens drawn early during acute phase of infection or soon after vaccination may be negative for IgM- or IgG-class antibodies to this virus, respectively." Mayo Clinic: Varicella-Zoster Antibody, IgM and IgG (Separate Determinations), Serum: Caution (https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/61856)
"A total of 62 patients were included in this study, and VZV IgM antibody was positive only in 23 patients (37%). The estimated antibody-positive period after HZ (herpes zoster, shingles) onset was 3.5 weeks (95% confidence interval 2.8–4.6 weeks)...The positive rate of VZV IgM antibody in HZ patients has been reported to range from 10% to 70% according to the test method, test period, and clinical symptoms of the patients." The positive duration of varicella zoster immunoglobulin M antibody test in herpes zoster (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370824/)
"The absence of an IgM antibody does not mean you do not have a active infection. Chronic infections in various tissues can persist with no evidence of IgM." HHV-6 Foundation: HHV-6A/B Testing: IgM test (https://hhv-6foundation.org/patients/hhv-6-testing-for-patients)
"The HSV-1 IgM test result was negative despite the presence of a life-threatening acute infection, whereas the HSV-2 IgM test result was positive. False-positive results have been reported for both HSV and VZV (28, 29). Of note, IgM may not develop during active reactivation." Immunoglobulin M for Acute Infection: True or False?: (vii) Case 7: Comments. (http://cvi.asm.org/content/23/7/540.full)
I agree, we need more POIS people tested for viral pathogens before clear conclusions can be drawn. But I'm curious, what would a mast cell activation test reveal? Many different things (virus, bacteria, poisons, food allergies, autoimmune disease) lead to mast cell activation. But maybe there is some new information in it? Thanks again Muon for sharing your test, experiences and knowledge on the immune system. It has sparked some discussion.
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Hi Nas
So far, I'm researching zinc (http://jcm.asm.org/content/38/5/1758.full), essential oils (https://www.ncbi.nlm.nih.gov/pubmed/13678235) and Oleuropein (olive oil extract) (http://www.academicjournals.org/journal/AJMR/article-full-text/E09C2B158944) as molecules that can kill dormant herpes viruses by disabling the outer coat.
PDE4 (http://www.discoverpde4.com/) inhibitors (Theobromine (https://en.wikipedia.org/wiki/Theobromine#Pharmacology), Theophylline, curcumin) can inhibit JNK and herpes virus replication.
Unfortunately, I don't think anything on the market has been shown to completely rid the body of the virus. That doesn't mean we can't see big benefits!
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NI nanna, Nas, Muon and HOD,
Very interesting discussion.
It makes me wonder what specificity would lead HSV/viral infections to finally cause POIS, because those infections are so frequent ( chickenpox was endemic when I was a child, no vaccine back then), and there are so few POIS cases. I would be interest to see what specific genetic trait or specific metabolic default in immune system or else would finally lead from a frequent type of infection to a rare syndrome like POIS.
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Hey Nanna,
I'm trying currently some typical anti-inflammation medications ( Cetrizin and Diphenhydramine ) You think they would be sufficient to stop the inflammation? I'm planning on a 2 months trial.
Hey Qunatum,
Yeah, very interesting indeed. There is a weird trigger mechanic at play here; we experience inflammation when we orgasm/ejaculate - I even felt POIS when I smoked cigarettes.
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Hi Nas,
I don't take H1-histamine receptor blockers because long term use is associated with several brain diseases. See http://poiscenter.com/forums/index.php?topic=2502.msg21708;topicseen#msg21708 (http://poiscenter.com/forums/index.php?topic=2502.msg21708;topicseen#msg21708)
Any H1 blocker that makes you sleepy, does so by blocking acetylcholine receptors and temporarily shutting down portions of the brain.
Allegra (fexofenadine) is the only H1-histamine blocker that does not cause long term cognitive impairment. Allegra does not cross the blood-brain barrier or inhibit acetylcholine receptor. When doing a experiment recently to test if COX-2 was involved with POIS, I took the COX-2 inhibitor, indomethacin, and a H1 receptor blocker. But this was a one-time experiment focused on testing an idea about COX-2 and POIS. H1 blockers do stop histamine induced arachidonic acid (AA) cascades. But I am highly cautious against H1-histamine blockers for mental health reasons (except Allegra).
I believe that part of reason I can get full relief from all POIS symptoms is that I have removed arachidonic acid (AA) from my diet. Plants don't make AA but animals do. So by not eating meat and dairy, I don't need to take H1 and a1 blockers with my stack in order to stop AA release. I realize that a AA free diet is hard to maintain. I have even tried to cheat on my AA intake (it doesn't work). So if the POIS Cascade Stack + low AA diet is not for you, COX/LOX inhibitors could be the next best option.
In my opinion, COX-2 inhibitors and 5-LOX inhibitors are the only guaranteed ways to stop inflammation. The oxidative enzymes (COX-2, LOX, iNOS, TDO, IDO) are the last step before inflammation occurs. A list of natural COX/LOX inhibitors can be found here Cost effective alternatives for omega-3 (https://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561)
Curcumin is a good 5-LOX inhibitor if you are not trying to have a baby (start a family). Otherwise, it may be better to take tumeric which has many health benefits beyond 5-LOX inhibition. I haven't seen many good natural options for blocking COX-2, but vitamin D3, the PDE4 inhibitor theobromine and a good mix of antioxidants can help.
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Well I'm using Cetirizin which is far less likely to cross the blood brain barrier. But I'll also look into supplementation medication for safer use. And about eliminating AA by reducing meat is economically unsustainable for me because I live in Iraq and meat is a large factor in our every day cuisine. Not mentioning that meat here is far more efficient when it comes to energy per serving/cost compared to vegetarian options here.
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I can confirm, that Alpha-GPC of this stack does work very well before and after O, so even if you did not take something before, Alpha-GPC does make it better.
I used it with N-Acetyl-Tyrosine together.
After O, our dopamine-system is blocked (prolaktine) and we can fix it faster with Alpha-GPC and N-Acetyl-Tyrosine
I think this stack will fix our brainfog a lot faster:
Alpha-GPC 500mg - 1g a Day
Omega 3 [High Quality] (500mg EPA, 350 DHA)
Uridine Monophosphate 150mg
N-Acetyl Tyrosine 350mg (alternative: mucuna pruriens)
Vitamin B-Komplex (low dose)
This stack does fix the dopamine problem
https://corpina.com/uridine-supplement-stacks-help-repair-dopamine-receptors/ (https://corpina.com/uridine-supplement-stacks-help-repair-dopamine-receptors/)
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I have a feeling that Pois basically weakens our immune system or make it to malfunction. Many of the dormant infections(whether bacterial,fungal or viral) become active once the immune defence is interrupted by pois.
1.The healthy diet and supplements which work for many of us, some how prevents this immune system malfunction.
2.Good refreshing sleep also works for many in reducing pois, because it boosts the immune function.
3.Broad spectrum antibiotics like azithromycin also have helped a few of us in reducing pois.
4. Many of us have chickenpox and shingles more than the normal population. The chickenpox virus or other neural dormant infection may be the reason for some of us not tolerating hot or cold showers in the head or neck region.This I think may make them active again.
I am now going to try some natural antibiotics{Neem leaves,virgin coconut oil,Garlic,nacetylcysteine} for next one month. Turmeric is not included as it is said to be bad for sperm health and we are planning for a child.
Will post if I find any improvement.
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Acording to Muons case and his labs- https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+3-6+Th1Th2+part2-4%2BIL4gen+14-08-2015.pdf
I find this- about th1 dominence- https://www.selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/
This realy make sense , if things this guy saying are true.
He sad that he is geneticly predisosed to all this conditions, and he cured him self by lectin avoidence.
He claim to be solved all his problems (genetics colerated) by his diet and suplemetation acording wich dominance th1 th2 lso th17 involwed...
He mention brain fog , autoimune conditions, inflamation ,infections, ebv virus , hpv, fatigue, ibs, low t3, hi cortisol (because HPA acsic must copesate vith hi cortisol), low pregnelone, and most of our symptoms an this linked to diet (LECTIN fod avoidence),damaged gut flora microbiota ,lectins couse also leaky gut=autoimune conditions etc...
My modher have reumatoid artrytis, and now autoimune hashimoto(" i am geneticly same like her") people here claim that they are lowered antibodies with diet avoidence food etc..
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I agree, we need more POIS people tested for viral pathogens before clear conclusions can be drawn. But I'm curious, what would a mast cell activation test reveal? Many different things (virus, bacteria, poisons, food allergies, autoimmune disease) lead to mast cell activation. But maybe there is some new information in it? Thanks again Muon for sharing your test, experiences and knowledge on the immune system. It has sparked some discussion.
I haven't posted here in a long time, but I have been reading the amazing discussions. Thanks so much! I have tried the full supplement stack for some months and have experienced some improvement, but far from complete. Recently, I have had a blood test done for mast cell activation, specifically for serum tryptase levels (after reading up a bit on mast cell activation syndrome) The test came back negative. When I did the test, I was not in a POIS phase. The doctor suggested to repeat the test at a time when I would be experiencing symptoms. I'd like to hear your thoughts on how long after orgasm would be the best time to have the test done.
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I haven't posted here in a long time, but I have been reading the amazing discussions. Thanks so much! I have tried the full supplement stack for some months and have experienced some improvement, but far from complete. Recently, I have had a blood test done for mast cell activation, specifically for serum tryptase levels (after reading up a bit on mast cell activation syndrome) The test came back negative. When I did the test, I was not in a POIS phase. The doctor suggested to repeat the test at a time when I would be experiencing symptoms. I'd like to hear your thoughts on how long after orgasm would be the best time to have the test done.
I'd suggest from an hour before orgasm to two days later. But doing it at the same day almost guarantees it.
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Hey, Nanna et al,
So I was wondering how can the desensitization treatment work for the infection theory? According to this article: https://www.sciencedirect.com/science/article/pii/S2050116118300199 Improvements were noticed after about two years of intralymphatic immunotherapy.
This theory basically proposes that there is an Immune reaction to the semen it self as if it had an antigen that the body reacts against. So how would this make seance in a the infection context ?
Maybe the dormant viruses are triggered by a component in the seminal fluid ? Perhaps while the body is busy getting rid of the semen from our blood stream, the immune system weaken and that triggers the virus ? Very curious.
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Hi BluesBrother,
I have been checked for tryptase before and 1-2 hours after orgasm, all negative, same thing for my brother. There are a few other poiscenter members who also have negative results.
Maybe this can be helpful:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC303860/
You will often detect no elevated tryptase in MCAS/POTS patients:
http://n.neurology.org/content/84/14_Supplement/P1.277
Perhaps this lack of tryptase could be explained by a subtype of mast cell, the MCC, which does not store tryptase or selective release plays a role:
''Subtypes of human MC are distinguished by the presence or absence of different serine proteases in their granules (i.e., tryptase+/chymase−: MCT, tryptase+/chymase+: MCTC, and tryptase−/chymase+: MCC)''
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231949/
MCAS and immune system:
https://www.drlam.com/blog/mast-cell-activation-syndrome-the-immune-system-gone-wrong/32795/
''MCAS is a condition that affects multiple systems, generally in an inflammatory manner. Symptoms typically wax and wane over time, varying in severity and duration. Many signs and symptoms are the same as those for mastocytosis''
https://en.wikipedia.org/wiki/Mast_cell_activation_syndrome
If I were you I would try something else like N-methylhistamine (24h urine), PGF2 (24h urine) or ECP, testosterone, IL-8, Th1/Th2/Th17, tryptophan, serotonin, IgG subclasses etc.
Interesting papers:
''Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions''
https://www.ncbi.nlm.nih.gov/pubmed/26813805
Perhaps in POIS there are mast cell being activated in the genitourinary tract and the intensity of the reaction is related to the high density of mast cells. Just throwing some ideas out here (MCC receptor mutation?). Also most MCC's (subtype) are located in mucosal surfaces instead of bulk tissue.
Neuroendocrinology of mast cells:
https://www.ncbi.nlm.nih.gov/pubmed/28094875
Link between mast cells and bacteria:
https://www.ncbi.nlm.nih.gov/pubmed/28818263
Dysbiose---->LPS---->Toll like receptors of Mast cells?? (TLR inhibitors for pois? Naltrexone is a TLR-4 inhibitor I believe)
Mast cell phenotypes release different cytokine profiles:
https://www.scopus.com/record/display.uri?eid=2-s2.0-0029044126&origin=inward&txGid=20008153e1a7803e00db05f537622925
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Hey, Nanna et al,
So I was wondering how can the desensitization treatment work for the infection theory? According to this article: https://www.sciencedirect.com/science/article/pii/S2050116118300199 Improvements were noticed after about two years of intralymphatic immunotherapy.
This theory basically proposes that there is an Immune reaction to the semen it self as if it had an antigen that the body reacts against. So how would this make seance in a the infection context ?
Maybe the dormant viruses are triggered by a component in the seminal fluid ? Perhaps while the body is busy getting rid of the semen from our blood stream, the immune system weaken and that triggers the virus ? Very curious.
The desensitisation works because it corrects the immune system. Allergy occurs when a person's immune system reacts to substances in the environment that are harmless for most people. So once the allergy(semen allergy) is overcome by desensitisation, immune defence is in healthy state. Therefore no dormant infections(viral,bacterial or fungal) can become active. This basically cures our POIS, if it is caused by dormant infections becoming active.
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Hey, Nanna et al,
So I was wondering how can the desensitization treatment work for the infection theory? According to this article: https://www.sciencedirect.com/science/article/pii/S2050116118300199 Improvements were noticed after about two years of intralymphatic immunotherapy.
This theory basically proposes that there is an Immune reaction to the semen it self as if it had an antigen that the body reacts against. So how would this make seance in a the infection context ?
Maybe the dormant viruses are triggered by a component in the seminal fluid ? Perhaps while the body is busy getting rid of the semen from our blood stream, the immune system weaken and that triggers the virus ? Very curious.
The desensitisation works because it corrects the immune system. Allergy occurs when a person's immune system reacts to substances in the environment that are harmless for most people. So once the allergy(semen allergy) is overcome by desensitisation, immune defence is in healthy state. Therefore no dormant infections(viral,bacterial or fungal) can become active. This basically cures our POIS, if it is caused by dormant infections becoming active.
Right, that's exactly what I was thinking about. Yet it's kind of odd that it's a case of both: Semen allergy and then a dormant infection happening at the same time. I mean; I have dust allergy, why wouldn't that activate the dormant infections ?
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Hi Nas
Dust allergy can also weaken the immune system if it is very severe. Many of the patients with severe respiratory allergies usually are much more prone to both upper and lower respiratory tract infections, than the common people. I myself have severe nasal allergies and get frequent sinus infections.
It seems Pois was very common in ancient India as per Ayurvedha (a Indian medical system). They knew very much about the disease but could not find the cure. So instead they made a warning that
"semen is very precious and it takes enormous amount of blood,energy and vital body resources to produce a drop of it. Hence it should never be wasted and if it is wasted it makes one to lose all his energy and vitality"
But now we know that Pois is spread worldwide. But only a very few have a luck to get treatment for it medically. Like Asthma and other allergies a complete cure may not be possible but medicines to manage it may be discovered in the future. Till then it seems we have to continue our experiments with supplements and diet !!
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In the (herpes) virus model, a stress-trigger activates a gene called JNK (https://en.wikipedia.org/wiki/C-Jun_N-terminal_kinases), and JNK activates the dormant herpes virus causing it to replicate and spread.
(https://i.imgur.com/GK8pPvh.png)
According to this paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681005/) (and press release (https://www.sciencedaily.com/releases/2015/12/151209143105.htm)), the herpes viruses are kept dormant by methyl groups attached to the virus DNA. Methyl groups act as the off-switch for the virus. When a gene called JNK is activated, the methyl groups that were attached to the herpes DNA are eventually removed (demethylation). This DNA demethylation results in the virus replicating and spreading.
In this herpes model of POIS, as the virus spreads, the immune system attacks the herpes virus and herpes infected cells. The attack by the immune system on the virus causes inflammation and allergy, and you become sick. Therefore, in this virus model, POIS is an attack by a strong/healthy immune system on an invading/spreading pathogen (virus). The immune system is doing exactly what it is supposed to do, which is kill the herpes virus and any infected cells.
An HHV-3 infected person with a weak immune system would not get POIS. They would get shingles. Shingles occur when the immune system is weak and cannot fight the virus. And shingles can be triggered by stress.
The virus itself is not the main thing that makes you feel sick, even though it is doing some damage to your body. What makes you feel sick (POIS) is the immune system releasing different molecules (histamine, cytokines, reactive oxygen species, antigens, etc...) to kill the virus.
Hi Quantum,
Since JNK activation leads to the demethylation of herpes DNA, The spread of the virus can be stopped by methyl donors as long as you have a properly functioning homocysteine cycle (https://i.imgur.com/hq96vF1.jpg). Stopping the virus after it has already spread does not stop the immune system from attacking the newly deactivated virus. So genetic problems with methylation could be a confounding factor in POIS. Also there are different strands of HHV-3 and they have differing capacities to infect and spread. The chickenpox vaccine is a live virus strand of HHV-3, but it is the weakest know strand. So another possibility could be that those who are infected with stronger strands of the virus may experience more symptoms. Even if under-methylation or differences in HHV-3 strands are not unique factors for POIS, there could be other factors that are unique. Also, I thought you might be interested in this article "COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells (https://www.sciencedirect.com/science/article/pii/S1567576910001207)"
Methyl groups attached to the viral DNA turn off the viral replication. However, when the methyl groups are removed (demethylation), the virus can activate/replicate. So methyl donors (choline and betaine) and B vitamins (B12, B9, etc...) play an important role in causing the herpes virus to go dormant.
Hi Nas, My best guess now is that the stress-trigger for POIS (in the herpes virus model) is a combination of high prostaglandin E2 (PGE2) and low cyclic AMP. PGE2 is found in high concentrations in semen and can cross the blood-brain barrier. I assume the dust from your dust allergy does not cross the blood-brain barrier. So I wouldn't expect dust to cause and herpes dependent POIS. Thank you for sharing that your POIS is induced by smoking. That helps narrow down the list of stress triggers. Nicotine increases COX-2 and PGE2 (https://www.ncbi.nlm.nih.gov/pubmed/16317086).
Desensitization treatments may work by exposing the body to chronically elevated levels of PGE2 leading to gradual PGE2 resistance (Ref 1 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940832/), Ref 1 (http://www.jbc.org/content/249/11/3615.full.pdf), Ref 3 (http://www.fasebj.org/doi/abs/10.1096/fasebj.30.1_supplement.710.9?sid=165d6284-d0ae-491a-90e1-47795bbb0fdb&)). This is analogous to how high insulin levels lead to insulin resistance (diabetes).
cyclic AMP is involved with erections.
JNK has many stress-triggers:
- prostaglandins (i.e. PGE2 (http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(13)00081-3))
- PDE4 (https://www.nature.com/articles/ncomms2674) (breaks down cyclic AMP)
- cyclic GMP (http://www.jbc.org/content/274/48/34301.full)
- UV light (https://www.ncbi.nlm.nih.gov/pubmed/8895468)
- inflammatory cytokines (http://www.jbc.org/content/285/26/19910/F6.expansion)
- possibly insulin
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Thank you for sharing that your POIS is induced by smoking. That helps narrow down the list of stress triggers.
Hah! See, I knew that was important!
I assume the dust from your dust allergy does not cross the blood-brain barrier.
Yes Nanna but neither does my semen (I mean I hope not), so I still don't understand this aspect of this theory.
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Hi Nanna
An head shower(both hot and cold shower) or head bath(that is what we call it in India) brings to me all the symptoms of Pois some times even greater than pois. Add this to smoking trigger mentioned by Nas!
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Kurtosis wrote about herpes too
« Sent to: Shinjiro on: August 25, 2014, 04:59:55 PM » « You have forwarded or responded to this message. »ReplyQuoteDeleteI'm not sure we're in the same boat. I have no POIS symptoms anymore. I'm happy with that. If POIS has a genetic basis then I don't expect it can just be switched off overnight. If that's the cure you imagine, with no ongoing medication, then you may be disappointed. Perhaps, I'd be fine without a multi-vitamin and resveratrol. I haven't tried to find out.If POIS comes from a viral infection e.g. HHV-6 then it won't be curable as such. The patient would have to take anti-virals when there are flare ups of the virus. Interestingly, vitamin D is used as a treatment for Herpes and some people with Epstein-Barr report improvement with vitamin D. Low vitamin D also effects testosterone and dopamine levels. Complimentary supplements in treating viruses are lysine and resveratrol as lysine inhibits the virus while reseveratrol and vitamin D increase the immune response. Some people may have a problem with low BH4. If they do, good, they should treat it. If they don't, they have problems other than what I had and I can't help. If you have SIBO it will create nutrition problems, fatigue etc.. Get it treated. My guess is that there are different illnesses on this forum. Some people are mentally ill perhaps and their POIS is anxiety related. I can't fix all these problems so I went away. It is easier for me to be happy with my own good health rather than spend hours every day trying to convince other people I'm OK. Why would I, they'd just resent me for being better but not being able to help them. Drinking red-bull and taking vitamin D is taking vitamins and caffeine to treat POIS. If that makes you happy, keep going. But if vitamin D is really making you better then it's advisable to get tested by your doctor for viral infections, EBV, Herpes etc.. Explain to your doctor your fatigue symptoms and see if they can help. Just try to make yourself better and don't try to fix POIS for everyone. One thing I learned, doctors have some ability to treat fatigue related illnesses and to test for viruses, bacterial overgrowth, vitamin deficiencies etc. They have no idea how to treat POIS and telling a doctor you have it will just make them think you're a hypochondriac Regards, KReport To Admin
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Well he sounded feisty didn't he ?
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aswinpras06,
An article on heat-induced herpes virus activation in vivo. Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. (https://www.ncbi.nlm.nih.gov/pubmed/1312625)
COX-2 inhibitors suppress heat-induced herpes activation. Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation (https://www.ncbi.nlm.nih.gov/pubmed/15857277)
So when arachidonic acid is oxidized by COX-2, it produces prostaglandin E2 (PGE2). This seems to be important in heat-stress induced virus activation.
Rinat and All,
Kurtosis exited before I joined POIScenter. Did he also have a low arachidonic acid diet and methyl stack?
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An excellent article on chicken pox virus,its effect on enteric nervous system and importance of cellular methylation ability to prevent its reactivation.
https://www.wellnessresources.com/news/chicken-pox-and-shingles-virus-prevent-reactivation
Many of us have both chickenpox and shingles,gut problems and sinus issues. All this can be caused by varicella herpes zoster. Thats why acyclovir may have helped. But complete remission of this virus at present is not possible.
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Thanks Nanna!
Why hot showers or cold showers(especially in the head and neck region) worsen pois can now have some explanation.
If similar findings for all the other symptoms of pois point to a latent infection becoming active, then proper medical treatment for pois is very much possible.
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Acording to Muons case and his labs- https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+3-6+Th1Th2+part2-4%2BIL4gen+14-08-2015.pdf
I find this- about th1 dominence- https://www.selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/
This realy make sense , if things this guy saying are true.
He sad that he is geneticly predisosed to all this conditions, and he cured him self by lectin avoidence.
He claim to be solved all his problems (genetics colerated) by his diet and suplemetation acording wich dominance th1 th2 lso th17 involwed...
He mention brain fog , autoimune conditions, inflamation ,infections, ebv virus , hpv, fatigue, ibs, low t3, hi cortisol (because HPA acsic must copesate vith hi cortisol), low pregnelone, and most of our symptoms an this linked to diet (LECTIN fod avoidence),damaged gut flora microbiota ,lectins couse also leaky gut=autoimune conditions etc...
My modher have reumatoid artrytis, and now autoimune hashimoto(" i am geneticly same like her") people here claim that they are lowered antibodies with diet avoidence food etc..
Very possible, check your PM.
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Thanks aswinpra06 for sharing the link Chicken Pox and Shingles Virus: Prevent Reactivation (https://www.wellnessresources.com/news/chicken-pox-and-shingles-virus-prevent-reactivation). This is a very informative link. It discusses most of what we have be discussing. It also talks about the methylation/herpes connection and the gut-health/herpes connection which I wasn't aware of.
kingfisher recently shared with me a paper that positively identifies prostaglandin E2 (PGE2) as the required molecule for herpes reactivation (article (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614784/)). Previous papers had only showed that COX-2 inhibition could completely block herpes reactivation. But this paper shows that adding PGE2 to neurons after inhibiting COX-2 can still cause the virus to replicate. So the arachidonic acid (AA) cascade (AA/COX-2/PGE2) is the trigger for herpes virus replication. COX-2 inhibitors are already prescribed to treat sex induced headaches.
Nightingale (http://poiscenter.com/forums/index.php?topic=2305.msg19052#msg19052), Hopeoneday (http://poiscenter.com/forums/index.php?topic=2659.msg23385#msg23385) and others have post about the vagus nerve infection hypothesis (http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis) by Michael VanElzakker. The most useful idea that I find from Dr. VanElzakker's hypothesis is that the location of the infection matters more than the specific type of herpes virus. The location of the infected nerves will decide what inflammatory disease and what symptoms people experience as the immune system attacks.
I've been reading about how zinc sulphate and certain essential oils have virucidal (virus killing) activity against herpes.
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Hello,
I'm following this thread with great attention. I have been using acyclovir (antiviral) and posted about it in another thread.Then i read a comment there that the whole virus thing is being discussed here.
This is so promising for me and makes me think that my improvement on acyclovir is not a fake psychological placebo effect. may be time has arrived to pay the viral infection thing a big share of concern. I had chicken pox and mumps when i was a kid and they were so bad.
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Infection may be the most likely cause because our symptoms recede on their own after a few days. This is the case for most of the other common viral and bacterial infections which get cured mostly on their own without any antibiotics or treatment on our part. Garlic,Acyclovir working for some, points out to most likely a viral cause.
Normal people are not stressed by orgasm but we are, may be due a genetic defect. We do not get complete relief because the causative factor(viral,bacterial or fungal) still is not cleared and resides dormant only to be activated again in a physiological stress for our body, which for us is orgasm. Also what ever causes this infection, is smart enough to make us crave for orgasm so that it can infect us again. This is not the case for most other common infections which once get cleared will not attack us again and again as the one which causes pois.
Allergy medicines like anti-histamines,desensitization,niacin flush are working because, may be they prevent the dormant infection becoming active by removing the stress(orgasm) on our immune system. Without the stress our immune function is normal and hence the latent infection cannot replicate.
At present I am trying some natural antibiotics like neem,virgin coconut oil,oregano oil,apple cider vinegar and garlic.
Unlike prescription antivirals this can be safely taken for a very long time. If infection is the cause then this may provide some useful relief.
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Thanks POISrival for sharing your experience with antivirals on the thread "Acyclovir. A probable treatment that suggests POIS is a viral infection (http://poiscenter.com/forums/index.php?topic=2659.msg23372#msg23372)". I'll be following your updates and the experiences of others who are testing antivirals.
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Thanks Nanna1 for your replies and excellent scientific explanation.
I am not a science student and a finance guy from my school finishing years and in my post graduation. I did not take medicine though I had a chance to join (because of my good grades), due to the effects of pois from my teen years,which I am very much repenting now. Any way internet now helps to a great extent.
Most of your valuable explanations are helping me to understand a few points, based on which I am posting. Keep up your good work!
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My Bell's Palsy (and/or POIS) could be caused by things other than viral infections. For example M. Pneumoniae is able to infect the CNS and causes neurological manifestions (chronic or acute) without airway related symtoms which is not often discussed in medical literature: http://www.pedneur.com/article/S0887-8994(09)00210-0/abstract
Frequent detection of Mycoplasma pneumoniae in Bell's palsy (26% M.Pneumoniae vs 16% VZV reactivation):
https://www.ncbi.nlm.nih.gov/pubmed/14576947
''According to our results, M. pneumoniae is frequently associated with Bell's palsy. Thus, a routine screening for this pathogen, even in the absence of respiratory symptoms, is necessary.''
Cytokine production in M. Pneumoniae infections:
Th1 cytokines, IFN-g, IL-12, IL-18:
http://journal.chestnet.org/article/S0012-3692(15)34861-3/abstract
IL-8:
http://www.pedneur.com/article/S0887-8994(05)00165-7/abstract
Btw IL-12, 15 and 18 are all IFN-g inducing parameters. I expect at least one of these being elevated aside from the discussion whatever the cause may be.
Increased IFN-g/Th1 dominance and decreased CD57+ NK cells could indicate the body is battling an infection. An orgasm decreases IFN-g which gives the pathogen (whatever it may be) time to replicate/reactivate and create symptoms like joint pain which is typical for M. pneumoniae but again rarely discussed in literature (so much focus on Pneumoniae). Also symptoms may endure for days or weeks just like POIS. I've seen a case report where a patient who had a chronic infection of this species and also had elevated EA-p138 but I can't seem to find it anymore.
And is someone familiar with Viral DNA testing by PCR?
http://www.imd-berlin.de/leistungsverzeichnis/parameter.html?tx_ajdiagnostics_analyse%5Banalyse%5D=31241&tx_ajdiagnostics_analyse%5Btitle%5D=Cytomegalievirus-DNA&tx_ajdiagnostics_analyse%5Bsynonym%5D=CMV&tx_ajdiagnostics_analyse%5Baction%5D=showmod&tx_ajdiagnostics_analyse%5Bcontroller%5D=Analyse&cHash=aa00dfe0034eafdf06412c4b765f0aeb
http://www.imd-berlin.de/leistungsverzeichnis/parameter.html?tx_ajdiagnostics_analyse%5Banalyse%5D=30786&tx_ajdiagnostics_analyse%5Btitle%5D=Varizella%20Zoster%20Virus%20%28VZV%29&tx_ajdiagnostics_analyse%5Bsynonym%5D=&tx_ajdiagnostics_analyse%5Baction%5D=showmod&tx_ajdiagnostics_analyse%5Bcontroller%5D=Analyse&cHash=5730c181adfd1a848072ea4f9a4e6d17
Is it reliable? And does a positive result mean anything?
I just stumbled accidentally upon an interesting article relating PE, IFN-g and serotonin.
''From these results it can be concluded that PE occurs because decreased levels of serotonin. Decreased levels of serotonin are associated with increased levels of IFN-y.'' https://ijbs-udayana.org/index.php/ijbs/article/view/104
''it is estimated that 90 percent of the body's serotonin is made in the digestive tract'':
http://www.caltech.edu/news/microbes-help-produce-serotonin-gut-46495
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Hello,
I'm following this thread with great attention. I have been using acyclovir (antiviral) and posted about it in another thread.Then i read a comment there that the whole virus thing is being discussed here.
This is so promising for me and makes me think that my improvement on acyclovir is not a fake psychological placebo effect. may be time has arrived to pay the viral infection thing a big share of concern. I had chicken pox and mumps when i was a kid and they were so bad.
Hi POISrival,
How do you take acyclovir? is it one 200mg a day or more ?
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Acording to Muons case and his labs- https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+3-6+Th1Th2+part2-4%2BIL4gen+14-08-2015.pdf
I find this- about th1 dominence- https://www.selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/
This realy make sense , if things this guy saying are true.
He sad that he is geneticly predisosed to all this conditions, and he cured him self by lectin avoidence.
He claim to be solved all his problems (genetics colerated) by his diet and suplemetation acording wich dominance th1 th2 lso th17 involwed...
He mention brain fog , autoimune conditions, inflamation ,infections, ebv virus , hpv, fatigue, ibs, low t3, hi cortisol (because HPA acsic must copesate vith hi cortisol), low pregnelone, and most of our symptoms an this linked to diet (LECTIN fod avoidence),damaged gut flora microbiota ,lectins couse also leaky gut=autoimune conditions etc...
My modher have reumatoid artrytis, and now autoimune hashimoto(" i am geneticly same like her") people here claim that they are lowered antibodies with diet avoidence food etc..
''Intestinal mycoplasma infection causes destruction of villi and compromise of the intestinal barrier. This allows accelerated damage by lectins in grains (especially wheat), beans, soy, nightshade vegetables, and dairy)''
https://rawlsmd.com/health-articles/mycoplasma-the-most-common-lyme-coinfection
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Yess Muon I like this( resarch and conections to the root couse).
This is wery wery intresting. All this make hudge sense.
I will write post on this tumorow(all conections of me and this).
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Lyme disease can also cause many of the symptoms of Pois like brain fog,insomnia,slurring of speech
as per this article. Infection as a cause for pois is now gaining ground, but the exact infection is not clear.
Boosting the immune system with good diet(lectin avoidance diet works for a few of us),supplements and good sleep will work for most of us, which further confirms infection by some virus or bacteria(dormant ones getting activated) is what most likely causing all our miseries.
http://drjaydavidson.com/lyme-disease-affect-brain/
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Hi Nas
I take acyclovir 400 mg twice per day for now.
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Acording to this our imune sistem is always stayed active and newer become normal in balance like in normal people-
https://www.selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/
Inflammation after the following: Strep, mono (EBV), HPV, herpes, pneumonia, H. pylori or Cytomegalovirus. These are common infections that also invoke the Th1 system; in some people with a genetic predisposition like myself, the immune system remains active after these infections. In some environments, this may have been a survival advantage since you?d be more likely to survive into adulthood and bear offspring [R, R, R, R, R, R].
And becuse of that we maybe hawe trigered symptomes with eyaculation.
And this.
I hawe tick bayted in testicle at age 12, after that sewere pneumonia on both wings(hudge amount of antibiotics, after that severe acne(again some antibiotics for acne), in that period always sick because low imunity.
I think that i get pois in that periodand because genetics predisposition, guts destroyed because of all this antibiotics infections and bad diet at that period, autoimune stayed alert because all of that.
https://rawlsmd.com/health-articles/mycoplasma-the-most-common-lyme-coinfection
This is olso wery intresting(worning some troyan virus on site haw a aantivirus on comp).
https://fixyourgut.com/quinolone-antibiotics-and-their-effects-on-the-mitochondria-and-health/
lets resarch , i think that we are alone with this ilnes.
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Hey Nanna,
So I reflected on Quantum's opinion about your theory and he makes a solid point about the problem with this theory. http://poiscenter.com/forums/index.php?topic=2659.msg23413#msg23413
One of the problem I noticed is here :
The immune cells attack the virus-infected cells with inflammation through neurotransmitters (histamine), cytokines (IL-8), and free radicals (hydrogen peroxide, nitric oxide).
Many people suffer from a dormant virus yet they do not suffer from POIS like symptoms. And the immune system is supposed to keep the virus from activating yet in our case it activates.
You also mention that there are stress trigger elements in the activation yet many people have these elements in their day to day lives, yet no one complains from POIS like symptoms.
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Hi Nas and Quantum,
I have been thinking about the rarity issue with POIS, since the different herpes virus types are more common. I have an idea, but first I need to share some background.
I believe this below figure from "Virus Infections in the Nervous System (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647473/figure/F1/)" explains the immune response and may answer questions about T cells and possible immune dysfunction arising from a herpes infection.
(https://i.imgur.com/6BLbaSw.jpg)
A more detailed explaination can be found here (https://academic.oup.com/jid/article/186/Supplement_2/S171/2191269#89857105) in the first 3 paragraphs of the section titled "State of the Art".
Here is an update on the virus model. Herpes infection chronically elevates COX-2 in the infected cells (even while "dormant") (http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000777). Arousal/stimulation/intercourse causes the release of neurotransmitters glutamate and norepinephrine.
(https://i.imgur.com/x11wKsO.jpg)
This model incorporates the immune response mechanism described here (https://academic.oup.com/jid/article/186/Supplement_2/S171/2191269#89857105). In this case, chemotaxis (http://www.gluegrant.org/chemotaxis.htm) means T cell movement to the site of infection, and chemokines (i.e. IL-8) are types of cytokines that tell the T cells where to go.
A conjecture about the rarity of POIS:
Michael VanElzakker, the guy who proposed the vagus nerve infection hypothesis (http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis), believes that the causes of neurologic diseases are location specific. Meaning that the location of the infection will be the most important factor in creating symptoms of the disease. This seems to make sense. Alzheimers is largely a disease of the hippocampus (https://en.wikipedia.org/wiki/Hippocampus) and many different toxins, viruses, etc... in the hippocampus are independently associated with Alzheimers. Parkinson disease can be induced by various toxins and infections of the substantia nigra (https://en.wikipedia.org/wiki/Substantia_nigra) section of the brain. Muon recently pointed to the fact that Bell's palsy is independently associated with HSV-1, VZV and Mycoplasma pneumoniae infections. The main idea is that as the location of the infection changes, the type of disease changes.
I think there could be a POIS area of the CNS that when infected causes POIS. If a person's herpes infection does not cover the "POIS area", they would not experience POIS even if they experience other illnesses. Moreover, if a person has a herpes infection that covers the POIS area and many other parts of the nervous system, they may have POIS and many other transient and chronic diseases associated with the total infection coverage of the virus. If this is true, then this "POIS area" should be located in a part of the CNS that is only active during orgasm and have a high density of glutamate receptors. This is not a theory or hypothesis for the rarity of POIS among herpes infected individuals since I don't have studies or data (brain autopsies) to back it up. So this is technically a guess based on the fact that other neurological diseases are location specific. Below is a philosophical diagram of this POIS area - herpes infection idea.
(https://i.imgur.com/LiFMsdQ.jpg)
With that said, I think an infection cause of POIS should have at least these two properties:
1. able to be lay dormant (latent and not living).
2. able to be triggered by erection/orgasm neurotransmitters (glutamate, norepinephrine and histamine).
All of the herpes viruses have these properties and are triggered through the arachidonic acid cascade (AA/COX-2/PGE2/JNK).
As far as solutions go, a methylation stack (https://i.imgur.com/hq96vF1.jpg), vitamin D3 and a strong COX-2 inhibitor (https://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627) (taken with a prepack) may be the easiest and cheapest option for most people. Not all NSAID fit the medical definition of a COX-2 inhibitor. Over-the-counter NSAIDs like iboprofen and paracetamol do not function as COX-2 inhibitors and will not be effective (https://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627). Indomethacin is effective as a prepack supplement. Celecoxib (https://poiscenter.com/forums/index.php?topic=2358.msg19841#msg19841) is the most often prescribed (non-OTC) COX-2 inhibitor and may be the best choice (taken with a prepack). I have not tried Celecoxib.
I follow a low arachidonic acid (vegan) diet, so I don't need to take these meds to reduce PGE2. But I do need to take B vitamins, methyl donors and omega-3s. As long as I keep the diet and stack, I have no POIS symptoms. I keep a mostly vegan diet also for general health reasons unrelated to POIS.
I know I rushed through that, but I am no longer on vacation and I need to finish some of my work before I go out of town. But I hope to give a more detailed post soon.
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Thanks Nanna, for taking the time to share your ideas on POIS pathophysiology, even if you have much work to do for your personal career.
Methylation support, vitamin D3, Cox-2, and other anti-inflammatory substances, including natural anti-oxidants, low-inflammation-induding diet, non-pharmacological stress-managing methods, all have been shown to help at least some members . Even if we do not know yet if a chronic viral infection is implicated or not in POIS pathophysiology, it seems clear that blocking inflammation pathways in one or more of its paths, is beneficial.
Making hypothesis, and refining them, like you do, and adjusitng your hypothesis according to new data and questions, can only help in solving the POIS puzzle. You have a great scientific mind, and your positive involvement here is very good for all of the POIS community :)
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Natural compounds and inflammatory pathway modulation
Inflammation triggers
Stress Infection
Radiation Allergic immune response
Trauma/injury Arachidonic acid
Inflammatory diet
Inflammatory pathways
NF-Kβ Leukotrienes
IL-1,6 NO
CRP Lipoxygenase
COX-1 and -2 TNF-α
Prostaglandins Adhesion molecules
Thromboxanes Reactive oxygen species (ROS)
Collagenase/MVP Cytokines
Conditions modulated
Pain Atherosclerosis
Inflammation Thrombosis
Insulin resistance Autoimmune response
Cancer Neurodegeneration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011108/
A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX enzymes, COX-1 and COX-2. Both the enzymes act similarly, but selective inhibition (as accomplished by selective COX-2 inhibiting NSAIDs) can make a difference in terms of side effects.
Injury and celular trauma-AA acid relase.
Acordin to this science, AA is relesed only if there celular trauma(injury).
Whot can else be involved here besades virus and posible odher infections?
Acute cronic stres(our glands in brain prmanent stucked in flight-fight mode?)
I think think is big posibility of delayed food senzibility like lectins for exepmle in some poisers(and this triger autoimunity, pois, anxiety, stres,brain fog, hi cortisol?)
People with a Th1 system out of control tend to release more cortisol than the average person because cortisol decreases Th1-related inflammation, so the body activates your HPA system every time you get a Th1 spike to keep things in balance.
-
Hi Nas and Quantum,
I have been thinking about the rarity issue with POIS, since the different herpes virus types are more common. I have an idea, but first I need to share some background.
I believe this below figure from "Virus Infections in the Nervous System (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647473/figure/F1/)" explains the immune response and may answer questions about T cells and possible immune dysfunction arising from a herpes infection.
(https://i.imgur.com/6BLbaSw.jpg)
A more detailed explaination can be found here (https://academic.oup.com/jid/article/186/Supplement_2/S171/2191269#89857105) in the first 3 paragraphs of the section titled "State of the Art".
Here is an update on the virus model. Herpes infection chronically elevates COX-2 in the infected cells (even while "dormant") (http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000777). Arousal/stimulation/intercourse causes the release of neurotransmitters glutamate and norepinephrine.
(https://i.imgur.com/x11wKsO.jpg)
This model incorporates the immune response mechanism described here (https://academic.oup.com/jid/article/186/Supplement_2/S171/2191269#89857105). In this case, chemotaxis (http://www.gluegrant.org/chemotaxis.htm) means T cell movement to the site of infection, and chemokines (i.e. IL-8) are types of cytokines that tell the T cells where to go.
A conjecture about the rarity of POIS:
Michael VanElzakker, the guy who proposed the vagus nerve infection hypothesis (http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis), believes that the causes of neurologic diseases are location specific. Meaning that the location of the infection will be the most important factor in creating symptoms of the disease. This seems to make sense. Alzheimers is largely a disease of the hippocampus (https://en.wikipedia.org/wiki/Hippocampus) and many different toxins, viruses, etc... in the hippocampus are independently associated with Alzheimers. Parkinson disease can be induced by various toxins and infections of the substantia nigra (https://en.wikipedia.org/wiki/Substantia_nigra) section of the brain. Muon recently pointed to the fact that Bell's palsy is independently associated with HSV-1, VZV and Mycoplasma pneumoniae infections. The main idea is that as the location of the infection changes, the type of disease changes.
I think there could be a POIS area of the CNS that when infected causes POIS. If a person's herpes infection does not cover the "POIS area", they would not experience POIS even if they experience other illnesses. Moreover, if a person has a herpes infection that covers the POIS area and many other parts of the nervous system, they may have POIS and many other transient and chronic diseases associated with the total infection coverage of the virus. If this is true, then this "POIS area" should be located in a part of the CNS that is only active during orgasm and have a high density of glutamate receptors. This is not a theory or hypothesis for the rarity of POIS among herpes infected individuals since I don't have studies or data (brain autopsies) to back it up. So this is technically a guess based on the fact that other neurological diseases are location specific. Below is a philosophical diagram of this POIS area - herpes infection idea.
(https://i.imgur.com/LiFMsdQ.jpg)
With that said, I think an infection cause of POIS should have at least these two properties:
1. able to be lay dormant (latent and not living).
2. able to be triggered by erection/orgasm neurotransmitters (glutamate, norepinephrine and histamine).
All of the herpes viruses have these properties and are triggered through the arachidonic acid cascade (AA/COX-2/PGE2/JNK).
As far as solutions go, a methylation stack (https://i.imgur.com/hq96vF1.jpg), vitamin D3 and a strong COX-2 inhibitor (https://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627) (taken with a prepack) may be the easiest and cheapest option for most people. Not all NSAID fit the medical definition of a COX-2 inhibitor. Over-the-counter NSAIDs like iboprofen and paracetamol do not function as COX-2 inhibitors and will not be effective (https://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627). Indomethacin is effective as a prepack supplement. Celecoxib (https://poiscenter.com/forums/index.php?topic=2358.msg19841#msg19841) is the most often prescribed (non-OTC) COX-2 inhibitor and may be the best choice (taken with a prepack). I have not tried Celecoxib.
I follow a low arachidonic acid (vegan) diet, so I don't need to take these meds to reduce PGE2. But I do need to take B vitamins, methyl donors and omega-3s. As long as I keep the diet and stack, I have no POIS symptoms. I keep a mostly vegan diet also for general health reasons unrelated to POIS.
I know I rushed through that, but I am no longer on vacation and I need to finish some of my work before I go out of town. But I hope to give a more detailed post soon.
Thanks for the amazing graphics.
Demo
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Great job!
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I have question, if virus is the cause what might be some natural and safe methods to fight agianst it, or againat viruses in general?
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Hi Spartak,
I think a virus-targeted stack should have vitamins D3, B6, B9, B12, C. There are ready-made stacks for this (Emergen-C (https://www.emergenc.com/) and Airborne (https://www.schiffvitamins.com/brand/airborne)). I also think methyl-donors and methyl-cyclers are important (alphaGPC, TMG, SAMe, etc...). Methyl-groups on the virus DNA keep it dormant.
The next step I would take in building an anti-virus stack is to find a way of dealing with the omega-6 arachidonic acid (AA). My strategy is to remove all arachidonic acid from my diet by doing a vegan diet. Vegan does not necessarily mean healthy. It just means there is no animal fat. In addition to the vegan diet (no AA), I also supplement omega-3 DHA and EPA. From reading post from others on the forum, I realized that the (vegan diet + omega-3) aspect of stack was prohibitive for most people for various reasons (cost, food preparation, lack of vegan protein sources, etc...). So I started this thread (Cost effective alternatives for omega-3 (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561)) to look for an alternative way of cancelling out AA. The short answer is, there is no easy answer. There are many natural COX-2 and LOX-5 inhibitors, but they seem to have poor bioavailability.
"A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia (Feb. 22 2017) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/)":
I want to point people to this study where they treat fibromyalgia in humans with an anti-viral (famciclovir (https://en.wikipedia.org/wiki/Famciclovir#Herpes)) and a selective COX-2 inhibitor (celecoxib). In this study, they test the hypothesis that a dormant herpes virus is activated by stress and produces an immune response leading to disease (fibromyalgia). This could be viewed as the virus model (http://poiscenter.com/forums/index.php?topic=2502.msg23434#msg23434) for fibromyalgia.
Notice the date on the publication. This is new science!
"Migraine Headache Treated with Famciclovir and Celecoxib: A Case Report (Nov. 29 2017) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737915/)":
This study (in a human) test the idea of virus-induced migraine headaches. They treat migraines with the same medication combo anti-viral (famciclovir (https://en.wikipedia.org/wiki/Famciclovir#Herpes)) and selective COX-2 inhibitor (celecoxib). The migraines were correlated with a specific location of the brain (please see Figure 1 brain MRI and caption (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737915/figure/f1-17-020napier/)). It took 5 days of treatment before the patient saw a general relief of symptoms.
Why do they need both famciclovir and celecoxib? I'm not sure right now. If anyone can explain the synergy between famciclovir and celecoxib, please do.
From the Discussion section of "A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/)":
"...The clinical evidence supporting the drug combination (Famciclovir and Celecoxib) utilized in this study was first derived through care of the lead author's patients with irritable bowel syndrome (IBS). A number of chronic GI disorders, including IBS and reflux, are frequently comorbid with fibromyalgia (FM). IBS patients were initially treated with famciclovir, yet those also placed on celecoxib for arthritis were the patients who demonstrated a dramatic improvement. A number of these patients expressed gratitude that their fibromyalgia symptoms were also reduced with this combination therapy. This clinical experience led to the hypothesis that recurrent reactivation of a tissue-resident herpesvirus in genetically susceptible individuals could contribute to the symptoms of fibromyalgia..."
In that last line, the term "tissue-resident" means that the type of disease (fibromyalgia) is dependent on the location (a specific tissue) of the herpes infection.
In an FDA Phase IIa Randomized, Double-Blind, Placebo-Controlled Study, Famciclovir + Celecoxib was both effective and safer than placebo:
"The safety profile was especially encouraging. Despite the celecoxib component, gastrointestinal and nervous system treatment emergent adverse events were reported significantly more often in the placebo treatment group (GI: 29.0% vs 42.5%; nervous system: 17.4% vs 23.3%; active to placebo), and study completion rates favored active treatment over placebo (82.6% vs. 60.8%) (largely driven by higher placebo discontinuation rates due to adverse events and lack of efficacy). A Combination of Celecoxib and Famciclovir Is Efficacious in the Treatment of Fibromyalgia: Results of a Phase IIa Randomized, Double-Blind, Placebo-Controlled Study (http://acrabstracts.org/abstract/a-combination-of-celecoxib-and-famciclovir-is-efficacious-in-the-treatment-of-fibromyalgia-results-of-a-phase-iia-randomized-double-blind-placebo-controlled-study/)"
For now, it seems that (COX-2 inhibitor) celecoxib is a real therapeutic for herpes-dependent diseases. I know celecoxib is not natural, but in terms of relief, I haven't seen a better supplemental alternative yet for dealing with AA. I haven't tried celecoxib, so I have no personal knowledge about how to take it other than some general advice about COX-2 inhibitors. Not all COX inhibitors have equal potency and effects. (http://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627) Anyone considering celecoxib should discuss this option with a physician or your primary care doctor about any health complications, drug interactions and dosing instructions.
On the thread "[UPDATED] Antivirals. (https://poiscenter.com/forums/index.php?topic=2659.0)", some POIScenter members are experimenting with an antiviral-only solution using Acyclovir (Zovirax).
Thanks Spartak for your comments and questions! :) If you or anyone else can find a better way of dealing with arachidonic acid, please post your idea!
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Thank you nanna1, very useful.
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I believe this below figure from "Virus Infections in the Nervous System (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647473/figure/F1/)" explains the immune response and may answer questions about T cells and possible immune dysfunction arising from a herpes infection.
As far as solutions go, a methylation stack (https://i.imgur.com/hq96vF1.jpg), vitamin D3 and a strong COX-2 inhibitor (https://poiscenter.com/forums/index.php?topic=2597.msg22627#msg22627) (taken with a prepack) may be the easiest and cheapest option for most people. Not all NSAID fit the medical definition of a COX-2 inhibitor.
First, thanks for introducing that very good Cell review paper.
Secondly, I can vouch for the effectiveness of Celebrex (COX-2 inhibit) as one of my three pillars in the prepack that I take to cope with POIS (the other two being Quercetin and Cucumin+BioPeperin).
Celebrex is the only COX-2 that is still FDA-approved for human use in the US at this point.
Celebrex has a long half-life: 7.8 hrs
Celebrex penetrates brain-blood barrier very well.
Celebrex has the one of the lowest cardiovascular side-effect among common NSAIDs
risks:
Naproxen < Celecoxib < Piroxicam < Ibuprofen < Meloxicam < Indomethacin < Diclofenac < Rofecoxib (at doses more than 25 mg)
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001388 (http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001388)
http://www.emedexpert.com/compare/nsaids.shtml (http://www.emedexpert.com/compare/nsaids.shtml)
The effectiveness of Celebrex has been discussed many times before, including http://poiscenter.com/forums/index.php?topic=211.msg4801#msg4801 (http://poiscenter.com/forums/index.php?topic=211.msg4801#msg4801). My personal experience is that Celebrex is best used as part of the prepack. (no need for the morning after dose). Celebrex is also somewhat effective as an anti-dote to wet-dream for me, provided that I take it immediately after the ejaculation.
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Over-the-counter NSAIDs like iboprofen and paracetamol do not function as COX-2 inhibitors and will not be effective[/url]. Indomethacin is effective as a prepack supplement. Celecoxib (https://poiscenter.com/forums/index.php?topic=2358.msg19841#msg19841) is the most often prescribed (non-OTC) COX-2 inhibitor and may be the best choice (taken with a prepack). I have not tried Celecoxib.
My take on why ibuprofen is not effective:
Ibuprofen and Indomethacin do inhibit COX-2, but ibuprofen has really poor BBB permeability. Ibuprofen is not effective, if we assume COX-2 inhibition must occur inside CNS (I lean towards this hypothesis). And Ibuprofen's half life is too short, which suggests COX-2 might be suppressed for over 4-5 hrs post orgasm for a prepack to be completely effective.
Paracetamol:
it is not a NSAID, and does not have any of the goodies that COX-2 inhibitors can offer.
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Here is an update on the virus model. Herpes infection chronically elevates COX-2 in the infected cells (even while "dormant") (http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000777). Arousal/stimulation/intercourse causes the release of neurotransmitters glutamate and norepinephrine.
(https://i.imgur.com/x11wKsO.jpg)
This model incorporates the immune response mechanism described here (https://academic.oup.com/jid/article/186/Supplement_2/S171/2191269#89857105). In this case, chemotaxis (http://www.gluegrant.org/chemotaxis.htm) means T cell movement to the site of infection, and chemokines (i.e. IL-8) are types of cytokines that tell the T cells where to go.
I am skeptical about the role of glutamate and norepinephrine here.
I have personal experiences with high CNS levels of glutamate (e.g. by eating chinese food loaded with MSG) and norepinephrine (e.g. I was prescribed with Bupropion a while ago, which is a norepinephrine reuptake inhibitor). Neither one, or the combination of the two would trigger POIS-like symptoms.
The glutamate and norepinephrine levels I experienced in those cases were much higher and prolong than a typical orgasm, e.g. hours of insomnia. But I did not suffer from POIS the day after.
So there probably are one or more additional ingredients, such as mast cell activation, and IDO-TDO activation.
1. Mast cell activation syndrome has many similarities to POIS. some details can be found here
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282993/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930370/
And Celebrex has a strong mast-cell stabilizer effect.
The main question is how does an orgasm triggers mast cells? most likely not through NorE or Glu. I don't have an answer, but I am very happy to discuss any hypothesis anyone could provide.
2. Quantum has a long post on IDO-TDO activation: http://poiscenter.com/forums/index.php?topic=2090 (http://poiscenter.com/forums/index.php?topic=2090) I found it very helpful, because 5-HTP was very energizing during my POIS state. Celebrex is a IDO inhibitor. Curcumin/Quercetin are all IDO-TDO inhibitor.
I know probably everyone's POIS is slightly different. But maybe you want to give a try with Celebrex and 5-HTP, individually to see if you respond to them. Then try curcumin and Quercetin as well. (My total annual cost of these supplements/med is around USD $120)
I told my doctor that I have GERD/Heartburn (which is true), and she is happy to prescribe me Celebrex, which has the least gastric side effects among all NSAID. My insurance does not cover it, but it cost about $35 for 60 doses here in the US if you get the generic version.
These were my personal experience. Feel free to point out flaws in my logic above.
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No, because COX-2 is easily blocked by anti-inflammatory drugs and these drugs are not effective against Pois.
Are we 100% sure histamines and No levels are increased during Pois ? I don't thinks so. It seems, but it's not sure.
Anyway, you made a very good job.
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Nothing is certain until people start coming back with test results. More overlapping test results means narrowing down to the cause of POIS (there should be a common denominator). Bottom line is we need more people going to labs individually and report back to this forum sharing their results (including negative ones) plus we need a doctor setting up research with the NORD grant.
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No, because COX-2 is easily blocked by anti-inflammatory drugs and these drugs are not effective against Pois.
The COX-2 inside your brain is not easily reached by most anti-inflammatory drugs, due to the blood-brain barrier. Celebrex is one exception
Are we 100% sure histamines and No levels are increased during Pois ? I don't thinks so. It seems, but it's not sure.
I completely agree that we need to further develop these hypotheses into something testable, by blood works and other tests.
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Nothing is certain until people start coming back with test results. More overlapping test results means narrowing down to the cause of POIS (there should be a common denominator). Bottom line is we need more people going to labs individually and report back to this forum sharing their results (including negative ones) plus we need a doctor setting up research with the NORD grant.
Non-invasive lab testing involving central neural system is very hard. The brain-blood barrier makes most biochemical markers in the blood meaningless. That's why there is no blood test for depression etc, and scientists still do not have direct evidence on how exactly SSRI works.
I am afraid at this stage, most tests will be indirect and involving changing regiments, a lot of time and efforts involved.
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Article from Forbes Magazine: "Surprise! Arthritis Drug Celebrex Shown As Safe As Ibuprofen And Naproxen (https://www.forbes.com/sites/johnlamattina/2016/11/14/surprise-arthritis-drug-celebrex-shown-as-safe-as-ibuprofen-and-naproxen/#1c7401c87a0c)"
The title of this article is very modest. Celecoxib (Celebrex) was shown to be significantly safer than Ibuprofen and Naproxen in every tested category of risk.
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Article from Forbes Magazine: "Surprise! Arthritis Drug Celebrex Shown As Safe As Ibuprofen And Naproxen (https://www.forbes.com/sites/johnlamattina/2016/11/14/surprise-arthritis-drug-celebrex-shown-as-safe-as-ibuprofen-and-naproxen/#1c7401c87a0c)"
The title of this article is very modest. Celecoxib (Celebrex) was shown to be significantly safer than Ibuprofen and Naproxen in every tested category of risk.
Very interesting study indeed. Thanks for sharing it. I read the original study at: http://www.nejm.org/doi/full/10.1056/NEJMoa1611593
It compares an averaged daily dosage of 209mg Celecoxib (I usually need only 1x 200mg Celecoxib capsule per O) to a daily dosage of 852mg Naproxen or 2045mg Ibuprofen. The dosages of the latter two are fairly large but not uncommon for people with arthritis.
This study should make people feeling quite a bit easier for occasionally taking an capsule of Celecoxib for an O.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011108/
A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX enzymes, COX-1 and COX-2. Both the enzymes act similarly, but selective inhibition (as accomplished by selective COX-2 inhibiting NSAIDs) can make a difference in terms of side effects.
Thanks Hopeoneday for sharing this article ("Natural anti-inflammatory agents for pain relief" above). It has a lot of practical information! :)
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Hi Nanna, and everyone,
I stumbled upon an interesting wikipedia article about fatty acids and inflammation, that can help deepen, for interested members, the understanding of Nanna's POIS cascade hypothesis, in particular the part about AA and phospholipase, and also why EPA/omega-3 are useful in preventing inflammation:
https://en.wikipedia.org/wiki/Essential_fatty_acid_interactions
There is a section detailing the 3 mechanisms by which omega-3 are blocking AA inflammatory response: https://en.wikipedia.org/wiki/Essential_fatty_acid_interactions#Mechanisms_of_%CF%89-3_eicosanoid_action
There is also a special section for the AA cascade in the brain: https://en.wikipedia.org/wiki/Essential_fatty_acid_interactions#The_arachidonic_acid_cascade_in_the_central_nervous_system_(CNS)
I hope this will be useful for a better understanding of the role of AA in inflammation, and the usefullness of omega-3 fatty acids. We may still wonder exactly what chain of event triggers POIS, but however, we can work on blocking the AA cascade once triggered ( and it really seems to be at play in many POIS cases), even if we do not exactly know how it comes to be triggered. At least, this brings relief, at least in part of the POIS cases.
BTW, Nanna, I am currently working on a complementary hypothesis ( another neurotransmitter-related branch) about how ejaculation could come to trigger an inflammatory response in the brain.... more on that later, I have to test a bit on myself before.
And, I would like to know what software you use to create your nice diagrams, they are very clear and clean, with nice colors :)
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Good link on AA, Quantum! I like that they explain the different prostaglandin receptors (EP1, EP2,..., EP5) separately in the Complexity of Pathways (https://en.wikipedia.org/wiki/Essential_fatty_acid_interactions#Complexity_of_pathways) section.
I use Microsoft PowerPoint for the diagrams. They are mostly textboxes and shapes (and arrows). You can set the properties of the shapes (example tutorial (https://www.lifewire.com/place-picture-inside-a-powerpoint-shape-2767021)). :)
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Hi Nanna,
this particular section you are referring to, shows how complex the immune system is ! :)
Thanks for the info about the diagrams ! When I was in university, there was no Power Point, and minimal computer usage.... this was a while ago...hehe.... our diagrams were drawn freehand, or I remember using a really old version of MacDraw, on my now antique Macintosh Plus, but everything had to be actually drawn, there was no pre-formed arrows, or else.... and no colors, of course, it was in black and white !
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Nanna, great looking diagrams!
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Nothing is certain until people start coming back with test results. More overlapping test results means narrowing down to the cause of POIS (there should be a common denominator). Bottom line is we need more people going to labs individually and report back to this forum sharing their results (including negative ones) plus we need a doctor setting up research with the NORD grant.
Hey Moun, so I reflected on what you said, and I realized that I once actually did an EGG scan on my brain:
https://drive.google.com/open?id=0B1uR2kQKGjb5cmhZYnpZaDZtaE0.
I told the Doctor that I had inflammation in my brain after orgasm and he tested me based on that. When the scan was finished he didn't confirm that I had inflammation and he dismissed what I have as depression.
I wish if someone can read the scan properly and see if there is a sign of inflammation, because that would help a lot if I can use this as evidence that what I suffer if physiological rather than psychological.
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I agree totally with Romies.
The first step this forum should establish in my view, is listing 1 or several very specific tests that each POIS sufferer can get done. They would then upload these test results to this forum.
There are seemingly enough experts here that would be able to conclude further based on our test results.
Secondly, people should upload whether they have other conditions, and they should also be sent a table to fill out which shows exactly what they eat each day. This will enable the more technical experts on this forum with PHDs and relevant degrees to apply their knowledge to these statistics...
People should also include their type of POIS, what helps or triggers symptoms etc.
The research doesn't seem to be going anywhere, perhaps we can use the funds available to create a dynamic form which we can all use to upload and contribute relevant data, which we can later use to submit to doctors for analysis...
I would certainly be a participant in this.
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Thanks, Michael!
Regarding your question of diverting some or all of our funding to create a dynamic form: unfortunately NORD has no refund mechanism in place for our $31,000 POIS Research Grant.
NORD also decides - not us - who will finally be chosen to conduct this forum’s POIS research.
NORD is a very solid, reputable organization.
www.rarediseases.org
Michael, maybe we can all work together with the chosen research team and your very good ideas about member identification and data capture.
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Nothing is certain until people start coming back with test results. More overlapping test results means narrowing down to the cause of POIS (there should be a common denominator). Bottom line is we need more people going to labs individually and report back to this forum sharing their results (including negative ones) plus we need a doctor setting up research with the NORD grant.
Hey Moun, so I reflected on what you said, and I realized that I once actually did an EGG scan on my brain:
https://drive.google.com/open?id=0B1uR2kQKGjb5cmhZYnpZaDZtaE0.
I told the Doctor that I had inflammation in my brain after orgasm and he tested me based on that. When the scan was finished he didn't confirm that I had inflammation and he dismissed what I have as depression.
I wish if someone can read the scan properly and see if there is a sign of inflammation, because that would help a lot if I can use this as evidence that what I suffer if physiological rather than psychological.
The above data from Nas and this thread---> http://poiscenter.com/forums/index.php?topic=2680.msg23744
should both be placed in a new category (data only category) separated by their own thread.
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Well i tought obout this lately to open treed "post here all yours test results that we can compare" , that could help us a lot. But i didnt because asking people to post there private lab results seem to me not etic.
But we have no choice- isnt we?
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Nothing is certain until people start coming back with test results. More overlapping test results means narrowing down to the cause of POIS (there should be a common denominator). Bottom line is we need more people going to labs individually and report back to this forum sharing their results (including negative ones) plus we need a doctor setting up research with the NORD grant.
Hey Moun, so I reflected on what you said, and I realized that I once actually did an EGG scan on my brain:
https://drive.google.com/open?id=0B1uR2kQKGjb5cmhZYnpZaDZtaE0.
I told the Doctor that I had inflammation in my brain after orgasm and he tested me based on that. When the scan was finished he didn't confirm that I had inflammation and he dismissed what I have as depression.
I wish if someone can read the scan properly and see if there is a sign of inflammation, because that would help a lot if I can use this as evidence that what I suffer if physiological rather than psychological.
The above data from Nas and this thread---> http://poiscenter.com/forums/index.php?topic=2680.msg23744
should both be placed in a new category (data only category) separated by their own thread.
Yes and I really wish if someone can analyse it for signs of inflammation. It would do me great help if it confirmed that I have inflammation.
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Wow Nanna1, very interesting and detailed research there. I?ve only quickly skimmed but I will take a good look once I have time.
I am pharmacist and dentist. I don?t work as a pharmacist anymore though.
I?ve had POIS since 2012, I?m not sure how it all started but my theory is that it could have been a combination of roaccutane treatment for acne, excessive orgasms (twice a day), and coffee.
These are just my theories and I haven?t taken the time to delve further into it but your research has got me excited. Please feel free to pick apart and/ or prove these theories.
1. Roaccutane is a modified Vitamin A analogue, so it basically replaced my natural vitamin A for this synthetic version which may have changed the way my body responds to stress and orgasms.
2. Excessive orgasms sensitises the body to a ?threat? and makes it respond defensively to fight off this threat and started the change towards POIS
3. Daily coffee consumption, coffee is a diuretic which would cause your body to flush out vital nutrients which when not replaced would place the body under significant stress, the body?s response to stress would be pro inflammatory catabolic in nature
Like everyone here, I didn?t know what was happening with my body, eventually I saw a sexual health doctor who diagnosed me with POIS, I had some investigations done and all the blood work was normal. I saw an immunologist who said my symptoms were not consistent with a type 1 allergic response meaning I wasn?t having anaphylaxis/ ALLERGY to my semen.
He thought that my symptoms were a manifestation of neurologic inflammation.
So the inflammation is triggered along nerve pathways.
Ejaculation and orgasm is controlled by the sympathetic nervous system (SNS)
The SNS practically connects to the entire body which explains why the POIS symptoms are far reaching and affects every single part of the body from your head to your toes.
So how to stop the inflammation?
1. Remove the cause ? stop ejaculating, which is practically impossible
2. Use anti-inflammatory methods ? which is what I do but I haven?t been able to cure POIS yet.
My anti-inflammatory methods.
My POIS symptoms have become milder and I can recover up to 90% within 1 day if I complete all the steps.
1. Chiropractic adjustment of back and neck
2. Deep tissue massage full body
3. Gym session whole body rehab with machines
4. Epsom salt bath
5. Lumosity brain training
6. Take supplements and medicine
7. Sinus rinse
8. Peppermint tea, Pu Er Tea , Oolong Tea
9. Pelvic floor strengthening
10. Vocal workout
Chiropractic adjustment
- The neck is the information highway that connects your brain to the rest of your body
- POIS results in inflammation in the muscles around the neck
- A stiff neck results in poor information transmission between the head and the body
- Headaches, sore shoulders, brain fog, muscle pain and weakness, irritability and mood disturbances are related to the stiff neck
- All muscles connect to bone and allow movement of the particular limb
- Various neck muscles connect to the spine. Inflammation in the muscle results in tightness of the muscle and swelling which pulls the spine towards the contracted muscle and out of its proper alignment.
- Releasing the muscle through soft tissue work (targeted massage) and spinal adjustments removes the tension in the neck and relieves the associated symptoms.
- You should book a chiropractic adjustment for the same day you plan to ejaculate
- Absolutely vital for recovery
Deep tissue full body massage
- POIS is generalised inflammation of the muscles and other tissues
- The muscles become swollen and painful
- Swollen, painful muscles don?t operate properly as non-inflammed muscles
- Thus the muscles don?t support the joints adequately and you get joint pain
- You need to remove the inflammatory fluid from the muscles by massaging it out
- A deep tissue massages targets the sore spots on the muscles and relieves the tension and pain.
- It is a painful massage but you need to do it
Gym session
- Since the muscles are out of whack, you need to rehab the muscles with a good gym session
- Don?t push too hard since the muscles don?t function to their full capacity and you risk getting injured
- I use the machines at the gym since they?re easy and safe to use and isolate various muscle groups
- Start with the biggest muscle group, the legs, then work your way to the core, arms, back
- Jump on the bike, do cardio, get a good sweat out of the workout to also cleanse the muscles of inflammatory fluid
- Do push ups, squats, make sure to sweat a lot
- Go for a swim ? water provides a great environment for muscle rehab
- Aim is to get each and every muscle moving in its normal range of motion so that it can support everyday tasks and movement
- Do sets of 10 starting at a light weight and increase progressively
- Wear compression gear to improve circulation and remove inflammatory fluid from the muscles faster
- I wear Skins calf compression on both sides
- I wear elastic knee supports on both sides and also elbow supports now that I have tennis elbow
Epsom salt bath/ swim in the ocean
- Via the process of osmosis, inflammatory fluid can be drawn out of the muscles towards the outside of the body as you sit in a salt bath
- I use about 1kg of Epsom salt in a 150 L bath tub using warm water and submerging myself for about 30mins
- It can make you quite dehydrated so make sure to drink plenty of water and replace electrolytes
- Drink hydralyte or Gatorade/powerade ? make sure to rinse out with water since these drinks are acidic and will cause acid erosion of the teeth over time. Can also use a fluoride mouth wash after drinking your electrolytes
- You need to drink electrolytes because the electrolytes in your blood have moved into your muscles so it is low in the blood and needs to be replaced
- If you don?t replace electrolytes, then you don?t get maximal extraction of the inflammatory fluid in the muscles
- The body self regulates and will try to retain fluid when the body is dehydrated so you need to treat the dehydration with electrolytes
- Go soak in the ocean achieves a similar result and is probably better since you can move freely whilst floating in the water
Lumosity brain training
- Brain fog is inflammation in the brain
- Principle is to use exercise once again to clear the inflammatory fluid
- Push ups in plank position is great for pushing fresh blood into the head and clearing away toxins and metabolites to speed up recovery
- Lumosity brain training is fantastic in that it provides categorised games that target a different attribute. The games focus on speed, memory, attention, flexibility, problem solving
- This game is worth subscribing for the lifetime which ends up being cheaper in the long run
- Once you?ve mastered the games, it can get a bit boring so you can find other brain training games to give your brain a workout and clear the brain fog
- The games are quick and easy to play taking about a minute per game
- Reading gets the brain ticking as well
- Information processing, problem solving, anything that gets the brain thinking will help
Supplements
These supplements are mostly anti-oxidants and may be in higher demand when the body is stressed during POIS. I prefer to take the maximal dose according to the packaging. If unsure check with your health care professional.
- Vitamin C 1000mg daily
o Vitamin C is a cofactor in collagen synthesis, collagen is found in connective tissue and essentially all over the body
o Inflammation of the muscles causes damage to the muscles and hence you need to repair it. Vitamin c helps with the repair process
- Magnesium 150mg daily
o Magnesium is required for muscle contraction, low magnesium leads to muscle spasms
- Mega B complex daily
o B vitamins help regulate stress and improve energy production in the body, so it helps to counter the stress of POIS on the body
- coQ10 600mg once or twice daily
o CoQ10 is a cofactor in ATP synthesis which is an energy molecule. It helps with energy production in the body and is supposedly depleted with age
- N-acetyl cysteine (NAC) 600mg daily
o NAC is an antioxidant which supports liver function, the liver metabolises toxins and removes it from the body
- Probiotics30 billion CFU
o Required for gut health. Gut inflammation arises from POIS and hence the intestinal barrier to infection is weakened and you find yourself getting sick easily. Good and bad bugs reside in the gut. The gut acts as a barrier keeping these bugs out but when it is weakened with inflammation, some bad bugs get in and make you sick.
o Probiotics increase the number of good bacteria
- Curcumin 500mg
o Anti-inflammatory take before1 hr ejactulation
- Vitamin D3 5000iu 1 capsule weekly
o A lot of people are low in Vitamin D from lack of sun exposure
Medicine
Pseudoephedrine 30mg ? helps clear the sinus and brain fog
Phenergan 25mg ? antihistamine counters the inflammation and reduces the swelling in the muscles ? take 1 at night
Sertraline 100mg ? SSRI ? great for clearing the brain fog, great for premature ejaculation, take 50mg in the morning and 50mg half an hr before sex. Get a prescription from your doctor
Bisolvon 100mg - for phlegm in the chest which is basically inflammation in the chest lining like in asthma
Ventolin 100ug ? to open the lungs and improve clearance of the phlegm and make it easier to breathe ? take 2-3 puffs as needed
Telfast 180mg ? antihistamine for swelling and sinuses, take 1 in the morning
Nurofen 200mg ? anti-inflammatory NSAID ? take 1-2 30mins before sex and afterwards as needed
Sinus rinse
- Get a flo sinus rinse, fill with water, add 1-2 sachets of the salt into warm water and use after POIS to counter the sinus inflammation
- This is a must. It is a bit daunting to do initially, stand over a sink, breath in and squeeze it into your nostril as you breath out and cough at the same time
- Takes some coordination but the water should go in from your nose and out the back of your mouth
- Blow your nose,
- Bend over tilt your head to the side so one eye is on top of the other and blow your nose then turn to the other side and blow your nose
Peppermint tea
- Is effective in irritable bowel syndrome which is inflamed bowels!
- Great for settling the bowels and reducing inflammation in the bowels and hence prevent break down of the gut lining and reducing the risk of infection and getting sick with the flu
- Make the tea 2 tea bags in a small volume of water and take it like a shot
Pu er tea
- Great for digestion problems, it seems to get the bowels moving
Oolong tea
- Anti-stress tea ? very calming
Pelvic floor strengthening
- I believe that weak pelvic floor is a driver for premature ejaculation and I suspect that spasms in the pelvic floor are a trigger for POIS
- Strengthening the pelvic floor will reduce premature ejaculation and it seems to lessen the POIS response
- Squeeze the muscle that hold in the piss, count to 100 and squeeze for each number, or count to 100 and squeeze from 1-100, repeat 5 times
Vocal workout
- I find I get a bit of a stutter once POIS hits
- This would be inflammation of the tongue and facial muscles
- Exercising the voice will get these muscles moving
- Count out loud 1-100 and squeeze the pelvic floor at the same time
- Count the alphabet
- Count the alphabet but call out the sounds ba ca da fa ga etc
o Then be ce de fe
o Then bi ci di fi
o Then bo co do fo
o Then bu cu du fu
- Repeat 5 times
- I usually do this in the car while driving to work so I don?t look ridiculous
Try it! It definitely works and is based on sound scientific principles.
If you do all this on the day of POIS you can recover quite quickly but I still find there is like a residual 10% of POIS that takes more time to shift
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Auuufffffffffffff melt whot did you yust wrote here ;D
Enything else to take? ;D
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I am pharmacist and dentist. I don?t work as a pharmacist anymore though.
I?ve had POIS since 2012, I?m not sure how it all started but my theory is that it could have been a combination of roaccutane treatment for acne, excessive orgasms (twice a day), and coffee.
Hi melt, and welcome to the forum!
Thanks for having taken the time to share your theory about POIS, and your POIS control method.
You have developed a very extensive method, fighting POIS on many different fronts, and it pays off for you, as you get a 90% of relief form your POIS symptoms.
I deduct from your method that your main symptoms are muscles pain and stiffness, sinus congestion, and some brain fog. I say "some" brain fog, because since you have managed to get two university diploma, your cognitive abilities are not that affected by POIS ( you may be aware that there are POIS sufferers who are drop out of College because of POIS, being unable to pass their exams, even if they were brilliant students in elementary school). You do not seem to have much emotional symptoms, like irritability, social withdrawal, impulsivity, mood swings, and the like... Am I wrong in thinking that?
Many parts of your method/program have been used and discuss here, some less ( like chiropractic adjustment ).
Take the time to read the wealth of information that is available on the forum, and I hope you will take an active part in our ongoing collective effort to solve the POIS puzzle.
Last but not least, you mention that a sex doctor has diagnosed your POIS. That is a rarity, since their is only a handful of doctors in the world who have heard of POIS, let alone knowing the criteria for diagnostic. I have currently put up a list of "POIS Doctors", meaning that they know about POIS and are seeing POIS patients ( and won't refer the patient to the psychiatric department...), and for now, there are only 3 doctors on the list. They do not have a cure to offer, but at least, you can skip the part where you have to educate the physician about POIS and convince him that it really exist... So, If you agree too, I would like to know the name of this doctor, so it can be added to this list ( see at http://poiscenter.com/forums/index.php?topic=2575.msg22338#msg22338 ).
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Recently, I have been experimenting with ways to cheat on my diet. For those just tuning in, I generally eat vegan foods to exclude the omega-6 arachidonic acid (AA) from my diet and supplement with omega-3. I did a test of indomethacin (cPLA2, COX-1, COX-2 inhibitor) and found that I can eat meat and cheese while taking indomethacin as a prepack ~30min prior to orgasm (see post (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773)). Indomethacin can replace my diet restrictions, but not my stack. I do not think indomethacin can be taken long-term because of its negative side effects.
Recently, I have been experimenting with conjugated linoleic acid (CLA). CLA is a naturally altered version of the omega-6 linoleic acid (LA), but CLA does not convert to AA. I found that I can eat meat once a day if I replace omega-3 with CLA in my stack. I still get full relief from POIS symptoms with CLA. I think, for some reason, CLA is more effective than EPA and DHA. So my stack is now updated here (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). I still think the omega-3s are good for general health.
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@nanna1:
Why did you quit eating meat in the first place? Did you have bad reactions to it or was it because of the theoretical argumentation relating to AA.
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Hi Muon,
I go on religious fast from time to time (not often). Sometimes they are short fast with no food just water (1 or 2 days). Other times they are longer fast with different food restrictions. I noticed that every time I fasted, my sicknesses when away. For example, during one of my 3 day fast (no food), the arthritis in hands and inflammation/pain in my knees when away completely. It initially got worse the first two days, but after the third day I no longer had knee pain or pain in my wrist. Also, my runny nose, sneezing, headaches and stiffness in my neck would disappear. This happen years ago and the knee pain and wrist pain never returned (healed). However, the runny nose, stiff neck and headaches returned once I was no longer on the fast.
On other occasions I have done what some people call a Daniel Fast named after the biblical character Daniel. The Daniel fast is one (vegan) meal a day for 3 weeks (no meat, egg, cheese, or any other animal product). Normally, my POIS symptoms would last a week. But I noticed that if I was on a Daniel Fast and was suffering from POIS, my symptoms would disappear after two days or less and they were less severe over all. I think that caloric restriction and the reduced stress from meditation and prayer played a big part in reducing symptoms and healing my arthritis.
However, I noticed that I get similar results (reduced allergy/sickness symptoms) from eating three vegan meals a day (no fasting required)! I did some test on myself eating isolated diets like only carbohydrates (bread and water) for a few days or only fiber or only vegetables or only fruits or only meat. I don't recommend anyone try this since it can lead to malnutrition. I found that eating animal fat by itself will give me mild POIS symptoms without orgasm. Also, animal fat makes my exercise sickness worse and I stay sore (DOMS) much longer.
Later I found out that drugs that reduced my DOMS also reduced my POIS. This all happened before I learned about methylation and B vitamins. The ones that reduced DOMS were COX inhibitors and H1-receptor anti-histamines. Experimental supplementation with AA omega-6, omega-3, and CLA led me to believe that AA was the cause of my DOMS and POIS since AA was the only thing that gave me headaches without having an orgasm and made DOMS worse. So, I started taking omega-3.
I have been eating out a lot lately with friends and there are no vegan options at these restaurants. I read some articles that CLA can control AA inflammation better than omega-3s, so I decided to give it another try. After about a week of taking CLA, I could eat meat (~5 times over a week) and have an orgasm without any back or neck pain. And now I can have orgasms without headaches while eating meat, but this is while taking the rest of my stack the same way. I think there is a significant difference between CLA and DHA and EPA. That is my experience. :)
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Hi Nanna,
for the benefit of members here, could you tell what CLA isomers are in the preparation you take ? There are many different CLA supplements on the market.
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Just to chime in about CLA - it?s apparently high in grass fed meats and butter. So going for only grass fed meat may be another option to get it in your diet. I certainly feel better personally when I just buy grass fed meat even though it costs more.
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Thanks Quantum for pointing out the CLA isomer issue, because not all CLA is anti-inflammatory. The brand that I use does not specify which isomers are present. So I can not fully answer your question. Not many of the manufacturers list this. MuscleTech is an exception (MT CLA (https://www.amazon.com/MuscleTech-Platinum-Ultra-800mg-Serving/dp/B00IUHNRCS/ref=sr_1_3_a_it?ie=UTF8&qid=1526350157&sr=8-3&keywords=muscletech+cla)). From what I understand, the active isomers are cis9,trans11 and trans10,cis12 CLA (Ref (http://www.jlr.org/content/46/10/2134.full.pdf)). Tonalin (R) and Clarinol (R) are proprietary 50:50 mixtures of these two isomers (cis9,trans11 and trans10,cis12). And several supplement manufacturers sell Tonalin (Amazon link (https://www.amazon.com/s/ref=nb_sb_noss_1?url=search-alias%3Dhpc&field-keywords=tonalin)). CLA is fat soluble, so I take it immediately before or during my meals.
In general, CLA changes body fat composition (changing the types of fat in the body). I think the effect of CLA on AA is caused by the same isomers that reduce body fat. So I would read the reviews and see which CLA supplements are effective at reducing body fat. I hope that helps. If you find/found any brands that specify the isomer ratios, I will be very interested!
Thanks caveeater for the tip on grass fed meat! I still don't eat meat everyday, just sporadically. But I'll have to look for some grass fed beef. :)
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Regarding CLA, I noticed that Examine.com writes [1]:
CLA does not go well with Resveratrol (Both possess anti-obesity actions, and inhibit each other in exerting them)
Would that warning apply here as well, or only when one wants to lose fat?
[1] https://examine.com/supplements/conjugated-linoleic-acid/
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Intresting to notice that some people hawe benefits by eating only meats and some specific food like goinglescrazy and they cured from pois when stick to that diet, on the odher side nana1 mentiened that meats cousing him pois and artritis etc.
Dos eny one of you done fodd senzibilitiy test from blod semple?
Delayed food sensibility, lgG test from blod.
Medicine dont admit and acept those testes but as reading on net people claim that hawe big benefits from those specific foodds restrictions.
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Hey I just joined the forum after reading through this thread. I think I might try taking the supplements suggested on the original post. I just had three questions:
1) Is that completely up to date with suggested supplements?
2) I've got severe gluten intolerance and have similar symptoms with POIS. I wonder if there might not be some connection there. I know it comes up from time to time around the forum so perhaps I'm not the only one. That being the case, it sounds like the supplement stack is more of a palliative approach to the problem, rather than stanching this issue at the source.
3) Many members seem to be extremely knowledgeable / medically savvy. I'm looking for organizations/research institutions dedicated to the research of our affliction. Is anyone aware of professional efforts to devise treatments? I'm on the board of a charitable foundation and am selfishly investigating ways to help.
Thanks!
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Hey I just joined the forum after reading through this thread. I think I might try taking the supplements suggested on the original post. I just had three questions:
1) Is that completely up to date with suggested supplements?
2) I've got severe gluten intolerance and have similar symptoms with POIS. I wonder if there might not be some connection there. I know it comes up from time to time around the forum so perhaps I'm not the only one. That being the case, it sounds like the supplement stack is more of a palliative approach to the problem, rather than stanching this issue at the source.
3) Many members seem to be extremely knowledgeable / medically savvy. I'm looking for organizations/research institutions dedicated to the research of our affliction. Is anyone aware of professional efforts to devise treatments? I'm on the board of a charitable foundation and am selfishly investigating ways to help.
Thanks!
Hi BuckarooBanzai, and welcome to the forum !
1. Nanna keeps his stack description updated ( original post). He is experimenting with other things, but those are mentioned in other, separated threads.
2. There are other members who seems to have a type of POIS responding to a diet change. You may like to read this thread : http://poiscenter.com/forums/index.php?topic=2275.msg18450#msg18450 . Member Going Less Crazy has 100% relief from POIS with his diet.
There are other links to other members' successful diets found in the POIS Types Chart, at type No7: http://poiscenter.com/forums/index.php?topic=2338.msg19448#msg19448
3. This forum have been working continuously, for years, to stimulate research on POIS. We have gathered a $31000 grant for a study on POIS, and it is currently available through NORD ( National Organization for Rare Diseases). We actively contact any researcher that knows about POIS, but to date, there is no answer to our Request For Proposal. You can find more information at http://poiscenter.com/forums/index.php?topic=2462.msg20970#msg20970 . We actively ask members to let their physician know about our RFP ( see http://poiscenter.com/forums/index.php?topic=426.msg24011#msg24011 )
However, studies on POIS are few and far between ( you can find an updated list here: http://poiscenter.com/forums/index.php?topic=2392.msg20182#msg20182 ). Research on POIS is quite slow, so we have to be patient and have reasonable expectations ( For my views as to why we have a hard time finding a research team that would go ahead with a study on POIS, see http://poiscenter.com/forums/index.php?topic=426.msg23844#msg23844 ). So , having some money to invest is not enough, medical research is a business, too. I hear you may have some funding available for POIS research, that is a great thing ! But we still have to find teams that are willing and interested to work on POIS.
Let us know of your results with any method you try for your POIS. Have you been suffering from POIS for a long time? What are your main symptoms?
Take a look at the wealth of information contained on the forum, and do not hesitate to ask questions and submit ideas and personal observations.
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Hey I just joined the forum after reading through this thread. I think I might try taking the supplements suggested on the original post. I just had three questions:
1) Is that completely up to date with suggested supplements?
2) I've got severe gluten intolerance and have similar symptoms with POIS. I wonder if there might not be some connection there. I know it comes up from time to time around the forum so perhaps I'm not the only one. That being the case, it sounds like the supplement stack is more of a palliative approach to the problem, rather than stanching this issue at the source.
3) Many members seem to be extremely knowledgeable / medically savvy. I'm looking for organizations/research institutions dedicated to the research of our affliction. Is anyone aware of professional efforts to devise treatments? I'm on the board of a charitable foundation and am selfishly investigating ways to help.
Thanks!
Hello BuckarooBanzai88. As Quantum said, welcome to the forum!
I was wondering how much have you been following your celiac diet. Are you noticing any overall improvement?
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Hi Quantum/Observer,
Thank you so much for all this information! I saw my doctor today to discuss this for the first time and it was very helpful.
It's also very, very helpful to see that compiled list of remedies folks have had luck with! I'm reading through them now to see which one to try first. I'll most certainly share everything I learn with my various investigations. I'm also probably going to go to the Mayo Clinic to make sure I don't have any underlying condition. I may try Crowdmed from there just to exhaust all of my resources.
That's interesting to hear about the politics and economy of research. This is all relatively new to me so I know next to nothing about, well, everything. Maybe as I learn more, I'll be able to contribute in some meaningful way to the goal of inspiring research. There too, I'll post anything I find out.
You asked how long I've been dealing with POIS. I've had underlying depression/anxiety/brain fog from gluten intolerance since I reached puberty (though I didn't know the cause). Only in 2012 did I really start to investigate why I was having such a hard time. Long story short, I figured out it was gluten (after a ridiculous procession of doctors) around 2016. Over 2016 I figured out just how sensitive I am and am now able to avoid it consistently. When I DO eat gluten, I become suicidal for about three days (extremely depressed, anxious, foggy head, exhausted, irritable), then over the next ~7 days, I slowly regain my equilibrium. I have nightmares about eating gluten.
But even after I stopped eating gluten (I'm on the extremely sensitive end of the gluten intolerance spectrum so I don't eat out ever, and I only eat what I cook), I realized there were inexplicable bouts of symptoms that were somewhat less severe, but very similar and usually only lasting for something like five days. More emphasis was on the physical fatigue in these instances. My normal 2 mile run is nearly impossible on the first day of these sorts of bouts. I only recently realized these instances coincided, in every single case, with having ejaculated. The intensity of my symptoms vary, but I haven't established the deciding factor there. Maybe quantity. At this point I'm celibate and only eat in alone. It's like living in a monastery or temple :). Of course I can't very well control what my body does while I'm unconscious.
At any rate, I've rambled here, but that's sort of my story since you and Observer asked. I'll let you all know (not on this thread since I think it's probably not the right place) if I learn anything new.
Thanks again for the warm welcome.
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Hi Quantum/Observer,
Thank you so much for all this information! I saw my doctor today to discuss this for the first time and it was very helpful.
It's also very, very helpful to see that compiled list of remedies folks have had luck with! I'm reading through them now to see which one to try first. I'll most certainly share everything I learn with my various investigations. I'm also probably going to go to the Mayo Clinic to make sure I don't have any underlying condition. I may try Crowdmed from there just to exhaust all of my resources.
That's interesting to hear about the politics and economy of research. This is all relatively new to me so I know next to nothing about, well, everything. Maybe as I learn more, I'll be able to contribute in some meaningful way to the goal of inspiring research. There too, I'll post anything I find out.
You asked how long I've been dealing with POIS. I've had underlying depression/anxiety/brain fog from gluten intolerance since I reached puberty (though I didn't know the cause). Only in 2012 did I really start to investigate why I was having such a hard time. Long story short, I figured out it was gluten (after a ridiculous procession of doctors) around 2016. Over 2016 I figured out just how sensitive I am and am now able to avoid it consistently. When I DO eat gluten, I become suicidal for about three days (extremely depressed, anxious, foggy head, exhausted, irritable), then over the next ~7 days, I slowly regain my equilibrium. I have nightmares about eating gluten.
But even after I stopped eating gluten (I'm on the extremely sensitive end of the gluten intolerance spectrum so I don't eat out ever, and I only eat what I cook), I realized there were inexplicable bouts of symptoms that were somewhat less severe, but very similar and usually only lasting for something like five days. More emphasis was on the physical fatigue in these instances. My normal 2 mile run is nearly impossible on the first day of these sorts of bouts. I only recently realized these instances coincided, in every single case, with having ejaculated. The intensity of my symptoms vary, but I haven't established the deciding factor there. Maybe quantity. At this point I'm celibate and only eat in alone. It's like living in a monastery or temple :). Of course I can't very well control what my body does while I'm unconscious.
At any rate, I've rambled here, but that's sort of my story since you and Observer asked. I'll let you all know (not on this thread since I think it's probably not the right place) if I learn anything new.
Thanks again for the warm welcome.
Do you have celiac disease? You might benefit going dairy free as well (gluten very similar to casein) and/or starting a food diary... especially if your gut isn't healed you could react to anything, especially grains and dairy.
Source: I have the same problem. Never truly figured out if it was celiac disease though.
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Regarding CLA, I noticed that Examine.com writes [1]:
CLA does not go well with Resveratrol (Both possess anti-obesity actions, and inhibit each other in exerting them)
Would that warning apply here as well, or only when one wants to lose fat?
[1] https://examine.com/supplements/conjugated-linoleic-acid/
Hi dizzy,
Thanks for your question. I do not know how CLA will affect results from Resveratrol. The bioavailability of CLA is much greater than Resveratrol. So I would imagine that the effects of CLA will dominate if they are taken together. But I do not take resveratrol, so I do not know the answer to your question. But thanks for asking. Hopefully someone else with experience with resveratrol can give better insight. :)
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Do you have celiac disease? You might benefit going dairy free as well (gluten very similar to casein) and/or starting a food diary... especially if your gut isn't healed you could react to anything, especially grains and dairy.
Source: I have the same problem. Never truly figured out if it was celiac disease though.
I don't technically have celiac disease. I have the genes for it, and the sensitivity, but it hasn't ever developed into full blown celiacs. I've been told by several doctors that I _must_ not eat gluten given my genes.
I don't eat dairy or eggs. I have a very restricted diet and I only eat home cooked from trusted sources. I definitely have some sort of leaky gut going that re-surfaces whenever i accidentally eat gluten.
Feel free to PM me if you have more questions about my specific condition. I feel guilty lingering on this particular thread since it's about nanna's stack.
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I have the genes for it, and the sensitivity, but it hasn't ever developed into full blown celiacs. I've been told by several doctors that I _must_ not eat gluten given my genes.
What genes?
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Hi, I suppose it is about DQ2 and DQ8 genes.
It also seems in my case, that some antibodies linked to celiac desease are increasing since I began with POIS.
My immunologist told me that once you are suffering an autoinmune desease you become more prone to suffer other.
I have recently got sores on my tongue. I went to the maxillofacial to see them. He told me that they are typical sores of an autoimmune disease.
although all this does not prove anything. all this makes me suspect that POIS is also an autoimmune disease.
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Definitly could be autoimune, an who knows what else involved. The prove for me on autoimune for some people is diet, check on GLC tread.
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Sorry, what do you mean by GLC?
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So I been quiet and thought to give good news to all. I thought to have finally found my POIS solution, after many many temporary victories over last decade. For last 2 months, a powerful drug cocktail containing active Glutathione 1000 mg (combined with strong pre-cursor to Glutathione pack of Cystein, Glutamine, Glycine, Alpha Lipoic) it worked as magic potion. First month POIS 100% gone despite getting 4-5 o's in a single day. In one month, I had about 16 pois free episodes of o's. However, since then its effectiveness has slowly waned. Last week it was not effective at all. Experience has taught me that POIS is very very tricky and it will trick you with your somatic processes, like your brain can control POIS if you have strength and strong belief. But this tahiti does not last long and your brain gives up eventually and back you are to your sick state where POIS manifests for 7 days. So I am back to drawing board.
Questions:
1. Has anyone tried for pois, 'Viagra' or similar vasodilator with success or failure?
2. Has anyone tried "SOD" - Superoxide dismutases?
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Sorry, what do you mean by GLC?
Going Less Crazy, a POISCenter Member.
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Sorry, what do you mean by GLC?
Going Less Crazy, a POISCenter Member.
Thank you Demo!
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So I been quiet and thought to give good news to all. I thought to have finally found my POIS solution, after many many temporary victories over last decade. For last 2 months, a powerful drug cocktail containing active Glutathione 1000 mg (combined with strong pre-cursor to Glutathione pack of Cystein, Glutamine, Glycine, Alpha Lipoic) it worked as magic potion. First month POIS 100% gone despite getting 4-5 o's in a single day. In one month, I had about 16 pois free episodes of o's. However, since then its effectiveness has slowly waned. Last week it was not effective at all. Experience has taught me that POIS is very very tricky and it will trick you with your somatic processes, like your brain can control POIS if you have strength and strong belief. But this tahiti does not last long and your brain gives up eventually and back you are to your sick state where POIS manifests for 7 days. So I am back to drawing board.
Questions:
1. Has anyone tried for pois, 'Viagra' or similar vasodilator with success or failure?
2. Has anyone tried "SOD" - Superoxide dismutases?
Hi Swell,
Sorry to hear that you treatment stopped working. That happens, so before concluding to long term effectiveness, it takes 2 to 3 months of reliable success.
About Viagra, there have been some mention of it, but no definite case of long term success. If you have ED or psychological inhibition, or you have less POIS when alone ( masturbation), sildenafil may ease the process in the context of a relation with another person, and lower POIS ( just an hypothesis, here). However, it has many possible side effects, and that is why it is on prescription only, so consult a health professional before using it.
I don't think there is any member that reported on using SOD on the forum, and a search from home page does not bring up anything substantial for superoxyde and/or dismutase.
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Hi Swell,
From my understanding, Superoxide dimutase (SOD) (https://en.m.wikipedia.org/wiki/Superoxide_dismutase) is a really large protein that gets digested in the stomach into smaller peptides and amino acids. I don't think any of the SOD gets absorbed through the intestines due to its large size and protein digestion.
SOD is made by the body from zinc, copper and manganese. So a mineral supplement containing zinc and copper and maybe some manganese should increase your SOD levels.
Also, most of the glutathione enzymes (https://en.wikipedia.org/wiki/Selenium_in_biology#Se-containing_biomolecules) require selenium. If there is a selenium deficiency, glutathione will have little effect. So maybe sodium selenite (http://www.lifeextension.com/Vitamins-Supplements/item01778/Super-Selenium-Complex) is a good mineral to add to the glutathione stack.
I notice that you take glycine and cysteine. These are both metal chelators meaning that they decrease/deplete minerals in your body. It could be that restoring minerals (copper, zinc, manganese, selenium, etc...) could restore your previous results. These are just some possible reasons. I wish you well!
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Just found this post on cure zone about Adrenal Fatigue, histamine and adrenaline(pois causes) and why niacin works for some people
"This is because the enzyme that degrades adrenaline, the enzyme COMT, requires niacin as a cofactor. It actually requires two things: SAMe and niacin, and giving niacin helps with both of those things.
I think that some people here might be interested in knowing why, so I will explain, because I think it also explains one of the underlying contributors to adrenal fatigue and how people with adrenal fatigue can improve their condition even more by just taking niacin more than once a day. By the way, I think you should be able to get the same effect using niacinamide without getting the flush. I stumbled on to all this while I was leaning how to help my son with fatigue and depression.
You (this is a general you, not directed any specific person) have to ask yourself ?Why do I have so much adrenalin?? Well, I think the reason is that you have histamine problems. Probably gut dysbiosis is the underlying cause and either gut bacteria are releasing histamine, especially when you eat, or leaky gut is causing food sensitivities causing a release of histamine, which may or may not give you obvious symptoms.
High histamine in the body requires high adrenaline to balance it, or your blood pressure would drop too low.
So why can't you get rid of the histamine so you don't need to make so much adrenaline?
There are two biological pathways to get rid of histamine. (And vitamin C gets rid of it for a little while if you take a ton of it.) The pathway that is designed only to get rid of histamine is the enzyme DAO, which is made in the gut and in other parts of the body. This pathway responds quickly to changes in histamine levels. The other pathway ? methylation ? does many things and responds quite slowly to changes in histamine. It takes a methyl group from SAMe and degrades the histamine with it. So if your DAO pathway is blocked, and you have to use the methylation pathway to get rid of histamine ? your body can't adjust the levels of SAMe to the constantly changing amounts of histamine, and part of the time you don't have enough and part of the time you have too much SAMe. At night the SAMe levels rise as your histamine levels drop and the production of SAMe stays the same, leading to an excess of adrenaline which you can't get rid of because although you have enough SAMe, your niacin has been used up by the DAO pathway in trying to get rid of the histamine.
So you will probably be saying ?What!?, niacin isn't a cofactor for DAO! DAO cofactors are Vitamin C, B6 and copper!? Well, that is true, but DAO is inhibited by its own product: imidazole acetaldehyde. Since the enzyme that degrades imidazole acetaldehyde, aldehyde dehydrogenase, requires NAD(P)+ (from niacin) to function, a shortage of niacin will lead to a feedback inhibition of DAO when the levels of imidazole acetaldehyde become too high. Magnesium may also be used as a cofactor in addition to niacin.
The niacin is needed for a step below the DAO step in the same pathway to get rid of histamine.
References below:
http://ajcn.nutrition.org/content/85/5/1185.full
See Figure 2.
?Histamine can be metabolized by extracellular oxidative deamination of the primary amino group by diamine oxidase (DAO) (2) or intracellular methylation of the imidazole ring by histamine-N-methyltransferase (HNMT) (3). Therefore, insufficient enzyme activity caused by enzyme deficiency or inhibition may lead to accumulation of histamine. Both enzymes can be inhibited by their respective reaction products in a negative feedbackloop ?
http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase
?The active site binds to one molecule of an aldehyde and an NAD(P)+ that functions as a cofactor. ?
So a lack of niacin is not only preventing you from getting rid of adrenaline, it's preventing you from getting rid of all your excess histamine, which is probably why you have excess adrenaline in the first place. And your need to get rid of the histamine is draining your niacin levels. So if you take niacinamide 3 times a day instead of just at night, you might just keep your histamine levels down to where you don't have to produce so much adrenaline! And your SAMe levels will be much more stable through the day if your histamine levels are kept low and you won't need as many supplements for the methylation cycle, because your SAMe won't be getting used up getting rid of tons of histamine. And your adrenal glands would probably enjoy not having to make so much adrenaline to balance out the histamine, and after they get a good rest, they might not be so fatigued!
P.S. You might need some extra P5P (B6) and also a couple grams of vitamin C a few time a day because I can tell you from experience that it does not work without the vitamin C. (I mean he DAO pathway won't work without vitamin C, you will still get rid of adrenaline during the night without Vitamin C, because by then the histamine will be gone already by the time you feel the adrenaline. I guess that as long as the adrenaline is balancing the histamine, you don't really feel it because it isn't in excess until the histamine is gone.)"
I also remember one user Haidcat writing that niacin works because it blocks noradrenaline convertion to adrenaline
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Hi thaniss, and welcome to poiscenter !
As you have seen in this post about Nanna's stack, methylation suport have been proven beneficial for some members.
Niacin role in POIS is still not well defined, because there are many possible mechanism for its effectiveness against POIS, but as you know, there are many members who have benefit by using it in prevention.
HAve you tried any of these?
About histamine metabolism, it is through that vitamin C helps getting rid of histamine excess, through DAO support ( I use this if I have some signs of allergy, and it does help). Vitamin B2, is also a cofactor for DAO, so it will support its activity as well. Methyl support will help eliminate histamine too, as it supports the main histamine elimination pathway, which is using HNMT.
For someone, like me, having a very slow Acetaldehyde Dehydrogenase enzyme, ALDH,( this shows, in particular, when you have a very low tolerance to alcohol, like I do), boosting DAO activity will produce more acetaldehyde, so more work for ALDH. So, when I need ALDH to be very active ( when taking some alcohol or suporting DAO for histamine elimination), I take some B1 ( about 25 to 50 mg) to help support ALDH activity. As a bonus, Vitamine C, taken for DAO support, is also a cofactor of Acetyl Dehydrogenase, ALDH2. I can add some cysteine or NAC ( n-acetyl-cysteine) because they also help getting rid of acetaldehyde by neutralizing it directly (acetaldehyde is a toxic by-product).
As often stated, there is not only one type of POIS but if one's symptoms are at least in part caused by excess histamine and excess acetaldhyde by-product, supporting HNMT, DAO and ALDH will be beneficial.
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So I been quiet and thought to give good news to all. I thought to have finally found my POIS solution, after many many temporary victories over last decade. For last 2 months, a powerful drug cocktail containing active Glutathione 1000 mg (combined with strong pre-cursor to Glutathione pack of Cystein, Glutamine, Glycine, Alpha Lipoic) it worked as magic potion. First month POIS 100% gone despite getting 4-5 o's in a single day. In one month, I had about 16 pois free episodes of o's. However, since then its effectiveness has slowly waned. Last week it was not effective at all. Experience has taught me that POIS is very very tricky and it will trick you with your somatic processes, like your brain can control POIS if you have strength and strong belief. But this tahiti does not last long and your brain gives up eventually and back you are to your sick state where POIS manifests for 7 days. So I am back to drawing board.
Questions:
1. Has anyone tried for pois, 'Viagra' or similar vasodilator with success or failure?
2. Has anyone tried "SOD" - Superoxide dismutases?
https://www.drdavidwilliams.com/why-you-need-glutathione
It?s also possible in many instances that the drop in glutathione levels may be related to exposure to heavy metals like mercury, lead, and cadmium. These metals steal sulfur groups from enzymes, protein compounds and/or peptides such as glutathione S-transferase (GST), an enzyme dependent on glutathione that studies have shown provides protection against the spread of cancer cells.
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Has anyone tried for pois, 'Viagra' or similar vasodilator with success or failure?
About 10 years ago, I thought I was having great
POIS-free success with Levitra (identical to Viagra), but then...it just stopped working.
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Has anyone tried for pois, 'Viagra' or similar vasodilator with success or failure?
About 10 years ago, I thought I was having great
POIS-free success with Levitra (identical to Viagra), but then...it just stopped working.
Niacin also works as a vasodilator. Beets, garlic or ginger work as well as vasodilator (thus lowering the blood pressure, as vessels open, there is less resistance for the blood to pass through them).
All of them seem to have worked at least to some extent, according to some members.
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Thankyou nanna1, Quantum, hopeoneday, demografx for your tips. nanna1 I do am taking a general mineral supplement which contain all minerals you wrote, I checked label it only has 100% daily values. Do I need to take mega-quantities? because the liposomal glutathione stack I am taking is a mega-quantity?
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I have tried Niacin (nicotonic acid 500 mg - which cause flush) with minor success. People with skin POIS like me can benefit. I only take it on POIS day. But I do take Nicotinomide Riboside 100mg daily. It helps develop NAD+ in your body. Does anyone know if that is equally good for POIS?
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... all this makes me suspect that POIS is also an autoimmune disease.
I think you have a lot of company here :)
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Nice to read the theories in this thread.
What I was wondering about: is there any way these theories can be tested, like by having blood-work done?
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Does anyone have experience taking Pregnenolone. I searched internet and there were some links to this very pois forum. Why do some people advice against taking it? I read about risk of Heart/Kidney disease, but then I also read it is Anti-aging?
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Not expert here. But blood work would reveal significant biomarkers to your health but not everything. Mitochondrial, cellular level health issues might not be detectable in a blood test. After all blood work only detect what is in blood only at a given time, just like urine test detect what is in urine only at a given time. A cellular biopsy would be more complete.
Nice to read the theories in this thread.
What I was wondering about: is there any way these theories can be tested, like by having blood-work done?
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Nice to read the theories in this thread.
What I was wondering about: is there any way these theories can be tested, like by having blood-work done?
Hi dizzy,
The answer to your question is YES! It is possible to rule out potential causes of POIS with blood test, MRI/CAT scans and other test. However, it is not so easy to prove a cause of POIS. So a process of elimination approach may be an effective way to test the theory.
A link to my blood test results can be found here (Gather and Post Here Your Medical Tests Results (http://poiscenter.com/forums/index.php?topic=2684.msg24052#msg24052)) along with test results of others. So you can use these test results as a guide to eliminate things/ideas/theories that probably are not related to the cause of POIS.
Also, other ideas for future test can be found here (Parameter input from members (http://poiscenter.com/forums/index.php?topic=2660.0)). Thanks for your question. I hope this was helpful.
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nanna1, Is fish like tilapia and salmon okay to substitute for meats.
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nanna1, Is fish like tilapia and salmon okay to substitute for meats.
Hi certainlypois2,
Good question. It may depend on the source of fish. Wild-caught fish tend to be high in omega-3, while farm-raised fish tends to be high in omega-6. The reason for this is that small fish (in the wild, oceans and lakes) get their fat from eating algae and aquatic plants which are high in omega-3. Larger (wild) fish get their omega-3 from eating smaller wild fish.
Fish that are farm raised are often fed animal stock or some other non-green protein source. So their food source is high in omega-6. I would stay away from any fish products that do not explicitly say "wild caught". Most of the fish where I live comes from a fish farm, so I tend to avoid it. But your case may be different. I hope this helps.
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Herpes Virus targeted stack:
Hi All, I recently wrote a summary/hypothesis of what I believe could be causing my personal POIS symptoms in a post on Ideas on Herpes Induced POIS (http://poiscenter.com/forums/index.php?topic=2683.msg24500#msg24500). In the POIS Cascade Stack (http://poiscenter.com/forums/index.php?topic=2502.0) thread, I compiled a stack that reflects my personal health philosophy and life goals. But, below is a stack that is solely based on what my test results say would be the best combination of supplements and drugs. It targets specific triggering mechanism of cytomegalovirus (CMV, HHV-5) and HHV-6 herpes viruses which are reactivated by neurotransmitters that cause PGE2 induced vascular stretching (RefSE (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). After looking at my test results and angiogram-MRI (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039), carefully going over test results of others, I tried the following stack:
Taken 45 minutes prior to sexual activity (prepack):
Vasoconstrictors:
---Excedrin (acetaminophen 250mg, aspirin 250mg, caffeine 65mg)
Methylators:
---S-Adenosyl methionine/SAM-e (200mg)
---Folate (200mcg)
---pyridoxine HCl/B6 (2mg)
---Cyanocobalamin/B12 (>100mcg)
NF-kB/cytokine regulator:
---vitamin D3 (2000IU)
Single trial notes:
1. After the O, there was some small drainage in my right nostral. I sniffed once and it went away. No symptoms for 15min.
2. Approximately, 20min after O, my skin started to tingle as if POIS was coming on. There was new drainage in my nose and I sneezed once. Then I took a second dose of Excedrin. Within 20min of the second Excedrin dose (this is after the O), all the of the symptoms went away. No drainage, no headache, no sneezing, 100% symptom free. I did feel tired, so went to sleep for 2 hours (long nap). But after waking up I did not feel any of the linguring fatigue associated with POIS.
3. Now it is the second day, and I am still completely free of POIS symptoms without taking any supplements (not even vitamin D3).
Most people are cautious about posting results of a single trial, but I have been testing and using vasoconstrictors (indomethacin, caffeine) for over a year now. So I know that they work. According to the reasearch, it is not the inhibition of blood vessel permeabilty that stops the virus activation and inflammation. So not all vasoconstrictors will work. But rather, the vasoconstrictors have to have specific properties that block NF-kB and COX signaling (RefSE (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). I discuss this in more detail here (http://poiscenter.com/forums/index.php?topic=2683.msg24500#msg24500). Also it seems that the fact that so many of the stacks on this forum stop working after a while is indicative of drug-resistance, which is a known property of pathogens.
The below supplements were not taken in the above trial, but can be stacked. However, consult your doctor before stacking multiple vasoconstricting agents as they can increase the risk of heart attack or stroke.
Enhancements:
---Trimethylglycine/TMG (methyl-donor) (2g)
---Indomethacin (COX inhibitor/antioxidant) (50mg)
---propranolol (beta2-blocker, blocks PGE2 induced vasodilation) (see personal doctor for details)
I and others on this forum have use indomethacin. It is so far the single most effective drug/supplement that I have tried (my indomethacin trial (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773)). But I am concerned about its long-term safety. That is the only reason why I don't used indomethacin. Excedrin is safer and as a compound drug, I find that taking two Excedrin doses 1 hour apart (before/after O) is more effective than single dose indomethacin. Indomethacin was shown to prevent CMV reactivation due to vascular stretching (RefSE (https://www.ncbi.nlm.nih.gov/pubmed/9686761)) and in one study it was the second most effective drug at preventing HSV-1 reactivation (Ref (http://www.microbiologyresearch.org/docserver/fulltext/jgv/41/1/JV0410010087.pdf?expires=1531322089&id=id&accname=guest&checksum=6F8696EC48E9EECDA0D07A74294B09A7)).
Methyl-donors and specifically S-Adenosyl methionine (SAM-e) reduce blood levels of histamine. In this way, SAM-e helps to constrict blood vessels (Ref (https://www.ncbi.nlm.nih.gov/pubmed/3961029)). Moreover SAM-e and folate are associated with improved endothelial function
(Ref (http://atvb.ahajournals.org/content/atvbaha/25/4/778.full.pdf)).
Final note, vasoconstrictors can increase your risk of heart attack or stroke. CMV and HHV-6 infections of the arteries do increase the risk of atherosclerosis. So consult a doctor before stacking multiple vasoconstrictors.
Update: I made a mistake in the amounts of methyl-donors that I originally posted. I have corrected the amounts.
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Thank you for your valuable suggestions Nanna!
I will personally be trying a vasoconstrictor stack: Indomethacin, Propanolol, Paracetol and Aspirin before orgasm, if the Endothelial theory holds true, then perhaps increasing vascular walls' integrity can decrease the level of permiability in the Endothelium and the Epithelium.
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Ok so I did try the Vasoconstrictor stack and here is the result:
I took 10mg Propanolol, 25mg Indomethacin, 100mg Aspirin and 250mg Paracetamol.
I waited ~45min and then I orgasmed, during this 45min I felt a little bit of flush effect where my skin was tingling and got a little bit high body temperature, added to that slight dizziness.
After Orgasm many of the symptoms I experience usually after Orgasm were reduced, I didn't feel as much fatigue, brain fog, dissconnection, etc. I am writing this currently after about an hour from O and I do feel slight cognitive symptoms like brain fog, speech problems and social anxiety but they are noticably reduced. To be honest I was a bit skeptic on the effectiveness of this stack given that I tried many NSAID's like Aspirin but they didn't do much.
But now I think there is a definitely a positive effect from this stack, and I'm probably going to increase the dose slightly next in hope of increasing its effectiveness.
Thank you again for your valuable suggestion Nanna! And I hope other members try this very simple stack to prove its effect.
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Hi Nas,
I'm glad you found some relief.
Ok so I did try the Vasoconstrictor stack and here is the result:
I took 10mg Propanolol, 25mg Indomethacin, 100mg Aspirin and 250mg Paracetamol.
I waited ~45min and then I orgasmed, during this 45min I felt a little bit of flush effect where my skin was tingling and got a little bit high body temperature, added to that slight dizziness.
I should say that I have never tried Propanolol (beta-blocker), so I don't know what it's effects are on the body. I did not experience these side-effects with the Excedrin-methylation-D3 test. So my first guess would be that Propanolol has something to do with that, but you would know before I would. The dizziness comes from reduced blood supply to the brain. I would think the dizziness is definitely a Propanolol side-effect. Both indomethacin and aspirin reduce platelets, which would increase blood circulation. So they would not cause dizziness.
After Orgasm many of the symptoms I experience usually after Orgasm were reduced, I didn't feel as much fatigue, brain fog, dissconnection, etc. I am writing this currently after about an hour from O and I do feel slight cognitive symptoms like brain fog, speech problems and social anxiety but they are noticably reduced.
That's good! I'm glad for your progress. From my experience, the cognitive symptoms from POIS come from neurotransmitters being depleted. Dopamine depletion causes irritability. Serotonin depletion causes depression. Acetyl-choline and NAD+ depletion causes brain fog and speech problems. There is some overlap in the neurotransmitter neurons, so I always just try to make sure all my neurotransmitters are at sufficient levels to function.
For cognitive issues, some people take neurotransmitter precursors (L-Phenylalanine for dopamine), (5-HTP for serotonin), (AlphaGPC for acetyl-choline) and (niacinamide for NAD+). This works, but for me a good methylation stack (SAM-e, TMG, B-Vit) takes care of the neurotranmitter/cognitive issues. From my experience, B vitamins alone are not good enough. I either need methyl-donors (alphaGPC, TMG, choline) with the B vitamins or I have to supplement neurotransmitter precursors.
To be honest I was a bit skeptic on the effectiveness of this stack given that I tried many NSAID's like Aspirin but they didn't do much.
I understand why many people who have tried aspirin or caffeine and had no results might be skeptical. Excedrin is a synergistic combination. Each of the three drugs in Excedrin (aspirin 250mg, Paracetamol 250mg, caffeine 65mg) have a much greater effect together than their individual components. Caffeine (adenosine blocker) enhances aspirin (COX inhibitor) and Paracetamol/acetaminophen (pro-cannabinoid) enhances caffeine and COX inhibitors. If you separate them, the results will not be the same. However, you can substitute indomethacin 50mg for aspirin 250mg. Indomethacin was shown to be a stronger anti-inflammatory (smaller RF numbers are better) (RefSE (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). Click below image to see full size.
(https://i.imgur.com/uB4XWx1.png)
Prostaglandin E2 (PGE2) is one of the main vasodilators on the body (Ref (https://en.wikipedia.org/wiki/Prostaglandin_E2)). Norepinephrine and histamine cause vasodilation by increasing PGE2 production. Indomethacin causes vasoconstriction by blocking COX and the production of PGE2. Below are some articles that discuss properties of indomethacin.
Increase in reflex vasoconstriction with indomethacin in patients with orthostatic hypotension and central nervous system involvement. (https://heart.bmj.com/content/52/5/581)
Coronary Vasoconstriction Caused by Indomethacin (https://www.nejm.org/doi/full/10.1056/NEJM198204223061614)
Cerebral vasoconstriction by indomethacin in intracranial hypertension. An experimental investigation in pigs. (https://www.ncbi.nlm.nih.gov/pubmed/8533921)
By the way, Paracetamol (acetaminophen) is a pro-cannabinoid (https://en.wikipedia.org/wiki/Cannabinoid). So Paracetamol may be able to replace CBD oil for people who use it in their stacks. I'm back taking my regular stack and vegan diet. The Excedrin was just a test.
But now I think there is a definitely a positive effect from this stack, and I'm probably going to increase the dose slightly next in hope of increasing its effectiveness.
Thank you again for your valuable suggestion Nanna! And I hope other members try this very simple stack to prove its effect.
Thanks Nas, I wish you well on your success.
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Hi Nanna,
Thank you for all the detailed responses. I started your POIS stack 3 weeks back. I notice the fatigue part is completely gone. However, my skin gets so hot (particularly on my back when I lay down) like I have fever. When I feel very hot, that makes my muscles tired (gets worse every summer). I dont know if anyone else have the same issue with body heat regulation
Questions:
1. In your original POIS stack post, you mentioned taking B6 and 200mg of folate along with Sam-E and alpha gpc twice a day. I saw in another post about cancer risk of using folate regularly. So, what is a safe daily dosage for folate?
2. Do you take Sam-E/b6/folate 3 times - 2 regular daily dose plus one when you use Betaherpesvirinae prepack?
2. In your recent update, you took EPA/DHA off, even though you recommend taking it for general health reasons. Do you see any problems taking CLA & EPA/DHA together? Or Should it be either/or ?
Thank you
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Hi SN,
Thanks for the questions,
1. The dosage posted on the original post (200 microgram) is a safe daily dose. For folate-cancer data, please see Table 1: cancer endpoints (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790187/table/T1/) under the Outcomes heading.
2. I only take The POIS Cascade stack (so Sam-E/b6/folate/etc.. twice daily) and maintain a (high-vegetable low-arachidonic acid) vegan diet. The type of diet is as important as the stack. I do not take Betaherpesvirinae prepack. I have tested the Betaherpesvirinae prepack. Most people choose not to do the diet because of cost, food taste, time of food prep, etc... So the Betaherpesvirinae prepack is for anyone who does not feel that the vegan diet is for them. However, the vegan diet has many health benefits beyond POIS reduction, and I believe my test results (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039) show this.
3. I don't see any problems with taking omega-3. Omega-3 is an essential nutrient for human health and mental health. DHA, EPA and CLA are all naturally occuring in the body, and I do not see an issue with taking them together. I crossed out omega-3 only for people who want to save money. For reducing POIS symptoms, I only need CLA (POIS Cascade stack + diet). I can stop taking DHA/EPA and still get full relief. So my reason for taking DHA/EPA is that it has many health benefits, too many to name here.
I'm not sure what's going on with the burning on your back. A doctor would have to run test to find out. But whenever I would have skin issues (burning, tingling, rash), I would put d-limonene essential oils like lemon oil or orange oil on the skin. d-limonene is bactericidal and virucidal, so it kills pathogens in the skin. Also it exfoliates dead and damaged skin cells. This should reduce future immune response in the skin. Vitamin C serums also work (bactericidal/virucidal/exfoliation). Just a thought. But I don't know why your back is burning. I hope something here was helpful.
One final note: If you find the Betaherpesvirinae prepack effective, it may be worth talking to your doctor about getting virus tested. This could help you customize your treatment more effectively.
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Hi All,
After recent post from Swell (http://poiscenter.com/forums/index.php?topic=2683.msg24625#msg24625) and POISse (http://poiscenter.com/forums/index.php?topic=2683.msg24648#msg24648), I decided to do another trial of indomethacin Friday night. I went to two parties (Wednesday and Friday) where meat was served. So I was not on my diet Friday during the trial (this was a coincidence). From my usual daily stack (POIS Cascade stack (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)) I only took vitamin D3 and CLA on Thursday and Friday morning. I took one dose of selenomethionine (100micrograms) Friday morning on an empty stomach (not part of prepack trial).
Here is my 2nd Indomethacin trial (Friday night):
Taken 2.5 hours prior to sexual activity
---indomethacin 50mg
---vitamin D3 (2000IU sublingual) (https://www.amazon.com/NOW-Vitamin-Liposomal-Spray-2-Ounce/dp/B0045MJNCU/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1531365035&sr=1-4&keywords=vitamin+d3+k2+spray&dpID=41iFg2gwtWL&preST=_SY300_QL70_&dpSrc=srch)
---Betaine-TMG (2g)
---N-acetylcysteine (1.2g)
---selenomethionine (60 micrograms)
---vitamin E (mixed gamma-E (https://poiscenter.com/forums/index.php?topic=2597.msg22716#msg22716), 700mg)
Experience:
Waiting two and a half hours is a long time to wait to start an orgasm. With that said, I did not experience any POIS symptoms the night of the orgasm. This is an improvement over my Excedrin trial (https://poiscenter.com/forums/index.php?topic=2502.msg24507#msg24507) where I had to take a 2nd dose of Excedrin after the orgasm to prevent POIS. Note: the optimum timing for indomethacin is 2 hours pre-orgasm even though I took it at 2.5 hours pre-sexual activity. It has a half-life of 4.5 hours.
Symptoms:
- The next day (Saturday) I woke up and did not feel any symptoms of POIS for the first 3 waking hours. I had energy and mental clarity. Then after about the 3rd waking hour, I had some drainage in my nose. So, I took a dose of N-acetylcysteine (600mg) and selenomethione (30mg) and blew my nose once. The drainage went away.
- During the middle of the day Saturday for a period of about 30min I felt some burning in my forehead as if I had a fever and some drainage in my left ear. I was at work at the time staring at a computer screen. I took a break from work and these symptoms went away within 30 minutes. I attribute this to work-stress, but it could also be POIS related. But I did not experience this on the Excedrin trial.
I went to work all day Saturday and ate lunch with a coworker. I was fully social and engaged as I usually am on my other stack+diet. I did not have any of the typical POIS symptoms (no neurological issues, fatigue, sneezing, etc...). Today (Sunday) I spent the entire day with friends playing games, and eating out. We had a lot of fun! Over all, the two (Saturday) symptoms listed above did not interfere with my productivity, moody or social life.
In my opinion, adding N-acetylcysteine and selenomethionine to this trial helped reduce some of the side-effects of indomethacin that I experienced before in my first trial. But this is hard to say for sure. POISse mentioned that he takes a second dose of indomethacin the next day after an orgasm (post (http://poiscenter.com/forums/index.php?topic=2683.msg24648#msg24648)). I think this advice would probably help reduce symptoms (1) and (2) since that was also what I tried in my first trial (see COX-2 inhibitors (http://poiscenter.com/forums/index.php?topic=2502.msg23222#msg23222) section). Also, thanks to POISse for figuring out the right dose timing for indomethacin (2 hours pre-orgasm (http://poiscenter.com/forums/index.php?topic=2683.msg24664#msg24664)). Egordon has shared his experience with indomethacin here (Post1 (http://poiscenter.com/forums/index.php?topic=524.msg5752#msg5752), Post2 (http://poiscenter.com/forums/index.php?topic=508.msg5773#msg5773)).
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Wery good work, but for people with all redy broken guts I dont know how will it be on long run with indomethacin etc.
NAC is capable of moving mercury to the brain from body tisues. (for thouse who hawe amalgams etc...)
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Hey Guys,
First off I want to thank Nanna for the original well thought out posts. I haven't fully dissected all the information but I've found something that worked for me. I've been studying biology/physiology and psychology for over 10 years and now I'm currently in nursing school pursuing NP. I've tried everything to cure this but I found something in your post that worked for me, the missing link.
My supplemental stack post orgasm is:
Calcium 600mg/Vit D 800IU
Vitamin C 500mg
Magnesium 500mg
Vitamin B1 250 mg
Aside from that I also take or do:
Master amino acid pattern
Vegan nutritional shake
Fish Oil
Probiotics
Intermittent fasting
I believe it is the high dose of thiamine that seem to eliminate most of my cognitive/mental/energy problems. I feel like I could write a novel on this but I'm going to keep it short and write some tips. I wanted to share this because it has taken a huge toll on my daily life and to find something that works is blowing my mind. I just want to share a few tips or pieces of information.
*Don't overdo it with masturbation and sex
*Don't abuse the supplements, for B1 you need rest periods and it is possible to gain tolerance. I would not take it everyday. High dose fast acting niacin was messing with my liver enzymes. It may seem harmless, just a vitamin but the effects on the body are far reaching and very complicated.
*Make sure you exercise everyday (Either many hours before sex or the next day after sex, unless walking) I prefer powerwalking mixed in with a handful of 5-10second sprints and a couple of 1minute jogging for 1 hour on the track in the morning. Nature walks are also good. Light calethstenics/weight workouts to maintain strength and muscle tone. Cardio for the longest time has been my go to to alleviate my symptoms faster, possibly something with adrenaline and increased blood flow to the brain. This is my second week trying my new stack but this time i didn't exercise and I don't feel as good as I did the first week. I also binged on a lot of food these past days. The first week was euphoric. Also in the past when my face went beat red from flushing it relieved some of the pressure in my head.
*Try to keep your blood glucose, insulin, and blood pressure in check but keeping a clean diet. Try to eliminate refined carbohydrates and reduce sugar intake. It is a lot of experimentation and documentation.
*Personally for me I did not respond well to Sam-e with orgasms. Similar to when I tried ssri with orgasms. SSRI+orgasm made things very bad for me. That is a whole new topic recently i did genetic testing and it might have to do with a mutation in my dopamine receptor and a gene encoding MAO.
*I have yet to try the other suggestions, I have to fully review the pro and cons and the remainder on the list to assess the effects it has on the rest of the body.
*Everyone is different so you may or may not need certain supplements or may have to adjust the dosage.
*I also believe there is a hormonal issue but which one I don't know, because they are all in someway intertwined.
*I'm also sensitive to cortisone, I develop pseudo-cushings syndrome from a few days of cortisone based products.
*This was a messy post, my apologies. Hopefully you can find 1 thing useful.
Thanks again Nanna, you are a wealth of knowledge!
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Welcome to poiscenter, Nurse 86 !
Thanks for sharing what works for you.
Am I mistaken to think that you are a girl? We do not have a lot posting here.
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Hi Nurse,
You mention that “I believe it is the high dose of thiamine that seem to eliminate most of my cognitive/mental/energy problems.” but do not have that specific amino acid in your stack - only an amino acid ‘complex’. Could you elaborate as well as provide the high dosage amount please?
Thank you
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Unfortunately, so far everything I've tried only has a good result if taken along with antihistamine or prostaglandin inhibitor (anti-inflammatory or analgesic). The way is to find something that works pre orgasm to avoid the exacerbated reaction of the immune system.
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My bad thiamine sounded like an amino acid but is vit b1.
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I'm a guy :D. What exactly do you take Fernando? I've taken various antihistamines and nsaids but they were ok. I've tried blood pressure medication. People kept on saying niacin but it was sometimes a hit or miss and it was starting to mess with my body. I've tried various herbal supplements like ginger root, fenugreek, tumeric, ect but really nothing substantial. My test from the doctor came back all fine. I literally was contemplating just getting chemically castrated because of the impact it has had on my life. I found something that works for me; it lets me function at a good level and I'm more than ok with that.
Anyway, I've tried thiamine through a complex of 25mg but that wasn't enough. The therapeutic value for me was 100mg-250mg. My original stack was just for relieving anxiety and social anxiety, which was made a lot worse with POIS. Right now, if I take my new stack I feel goooooodddddd. But that is also supplemented with a good diet, exercise, and proper sleep cycle. Can't feel good if you don't put in the work to give your body a fighting chance. Some people are genetically gifted so this doesn't apply to them.
Aside from that, finding a solution through a magic pill isn't going to cure everything because i believe it isn't just the immune system. Everything is connected in someway and right now I've been more heavily invested in hormones because of my subset of symptoms still present. I also do agree with you that an unnecessary immune response is occurring but that is just part of it. I also believe in some sort of neurotransmission imbalance (possibly enzymatic), brain-gut axis disregulation, wonky endocrine system due to maybe an over release of a hormone and neuroplasticity in the brain play a apart in this too. Some postsynaptic cells might have more receptors then others causing an increased response or the effect is prolonged because certain channels aren't resetting at appropriate times. Honestly I do not know. I also don't like taking medication because it seems to me it is a double edge sword.
Some bodies are different from others, like some can't have gluten or some have a sun allergy. There is no way around some of these things. Everything though we've made a lot of progress in the health care industry we still really don't know what the heck is going on. People with diabetes, high cholesterol, and blood pressure looking toward a pill to be healthier but instead it promotes the same poor lifestyle and they get unpleasant side effects. Our lifestyles have changed dramatically from our parents, and so has our diet. Our brain is overloaded with synthetic stimuli, poor nutrition, sedentary lifestyles, decreased social interactions and so forth.
I just read some of nannas posts he concluded that after taking Sam-e and B1 he was functional again. We also have very similar problem, including the generic diagnosis of ibs. For me I didn't take Sam-e because of a mutation in a gene regulating my catecholamines so i think it is the B1 vitamin responsible then. I suggest you read his posts because he knows his stuff lol. He is a very smart guy. You changed my life :D
Isn't NE=norepinephrine?
Also who is the dutch doctor?
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Hi Nurse,
I've also taken B1 a lot, in different forms, and I found it highly useful. But ... indeed, you can build a tolerance. And I have found that after a while of taking 300 mg a day, I got problems breathing. As in: I had to think about breathing, otherwise it felt like my body/brain just didn't do it automatically. Quite scary. At one point I was afraid to go to sleep. Fortunately, all turned out well, but I'm more careful with B1 now.
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I'm glad you shared that with us dizzy and I agree with you that the side effects can be quite scary. Especially the synthetic forms, you can gain tolerance and have withdrawal symptoms. All the most common prescriptions coming out of pharmacies will mess you up one way or another down the line and then they will prescribe more to treat your symptoms lol. You have to keep in mind that certain treatments put your health on the line just so you can get instant gratification. Also if you supplement too heavily the body might think oh I don't have to produce as much anymore of xyz. Try to keep things as natural as possible because honestly until we have some real powerful diagnostic tools in the medical industry, we really do know what is going on. Going to the doctors they all run the same generic tests hoping for a hit but, yea that is another topic.. Is it really worth it for an fleeting orgasm?
I'm just happy because now I can have a happy and responsible sex life and also function in society without having to heavily plan around it. I'm not using my stack so i can blow my load constantly. I'm grateful for it and I'm not going to take advantage of it. 1-2 a week max. For the supplements i do take regularly I make sure they are within range of obtaining them through dietary means. So low dose for daily life and then high dose, day of O. Pills can only do so much for us and the rest is based on our lifestyle. Do you have good friends, have good/healthy coping mechanism, exercise, eat well, and ect. For the past couple years I really zoned in on nutrition because that exacerbated my pois. Frozen foods, fast food, deceptive serving sizes (who eats 5 chips, I kill the whole bag lol), sodium, high fructose corn syrup, and ect. All this stuff causes inflammation through various reasons and mechanisms. Anyway, i'm rambling. Oh and dizzy I have 90percent of your symptoms.
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Nurse
I try to take only antihistamines. I avoid the anti inflammatory and analgesic and only take these in last case.
After orgasm I take Allegra D in the morning and Fenergan near bedtime because it is sedative.
When I need taking anti-inflammatory or analgesic take Tandrilax (Acetaminophen, Caffeine, Carisoprodol, Diclofenac Sodium) 1 tablet every 8 h, but this is the case I am in pain and tension in the spine.
I also drink coffee in the morning and afternoon and it helps keep my brain working well.
I took Arcalion 3 times daily (Sulbutiamine 200 mg) the last few times but it seems that the effect was not very significant. Maybe I have to increase the dose. Sulbutiamine is a potent form of vitamin B1 used to increase mental and physical energy.
I take 200 mg of taurine every time I have symptoms (3 x daily).
As I mentioned, the times I tried to take all this without the anti histamines, the effect seemed too small, which leads me to believe that the target is the release of histamine. What needs to be done is to lower this starting point. For me what works as prevention is the health of my spine and health of the vagus nerve. Postural exercises, Aerobic exercises and no stressed events near the time of the orgasm.
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I'm glad you shared that with us dizzy and I agree with you that the side effects can be quite scary. Especially the synthetic forms, you can gain tolerance and have withdrawal symptoms. All the most common prescriptions coming out of pharmacies will mess you up one way or another down the line and then they will prescribe more to treat your symptoms lol. You have to keep in mind that certain treatments put your health on the line just so you can get instant gratification. Also if you supplement too heavily the body might think oh I don't have to produce as much anymore of xyz. Try to keep things as natural as possible because honestly until we have some real powerful diagnostic tools in the medical industry, we really do know what is going on. Going to the doctors they all run the same generic tests hoping for a hit but, yea that is another topic.. Is it really worth it for an fleeting orgasm?
I'm just happy because now I can have a happy and responsible sex life and also function in society without having to heavily plan around it. I'm not using my stack so i can blow my load constantly. I'm grateful for it and I'm not going to take advantage of it. 1-2 a week max. For the supplements i do take regularly I make sure they are within range of obtaining them through dietary means. So low dose for daily life and then high dose, day of O. Pills can only do so much for us and the rest is based on our lifestyle. Do you have good friends, have good/healthy coping mechanism, exercise, eat well, and ect. For the past couple years I really zoned in on nutrition because that exacerbated my pois. Frozen foods, fast food, deceptive serving sizes (who eats 5 chips, I kill the whole bag lol), sodium, high fructose corn syrup, and ect. All this stuff causes inflammation through various reasons and mechanisms. Anyway, i'm rambling. Oh and dizzy I have 90percent of your symptoms.
Hi Nurse,
I totally agree that a healthy diet is important to lower POIS symptoms, and I also agree that once or twice a week is probably the most often we can have releases, even if we have a good stack/pre-pack to control our symptoms. More than that, the cumulative effect of POIS seems too much to handle.
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How come allegra-d? Have you tried antihistamines without pseudoephendrine? Personally I prefer benadryl for allergic reactions but it makes you drowsy. I would definitely not increase that dosage for sulbutiamine; 600mg is ALOT. If you take it more than you don't then you will gain tolerance and have withdrawal symptoms. The first week i tried my stack i did 2 os for 4 days straight and was good, along with my lifestyle regimen. The 5th day however was a different story. 2nd week I'm doing good again. 1st week was just a test and I literally sat on the floor saying to myself holyshoot, this is actually working for me.
Personally I think you are gaining benefits from the stimulants in your stack by activating your adrenergic receptors, pseudoephedrine is a strong stimulant from Allegra-D, Caffeine from your Tandrilax, Caffeine from your coffee and sulbutiamine but then you also have depressants. This is not a good long term solution though. You also say you don't get symptoms during sex which also leads me to believe your adrenergic system plays a role in it. I have to do more research if i'm not lazy lol. When someone has a severe allergic reaction, epinephrine is administered first hand and then possibly antihistamine 2nd. Masturbation is very low physical activity vs sex. Brain activation is also different such as talking to people through texting vs talking in person.
I've tried psuedoephedrine also in the past. It made me ejaculate when not having sex. In social situation i would be excited and stimulated (not sexually and then when i pee, i ejaculated.)
I'm interested in your vagus nerve suggestion as I do have pain but nothing substantial. My bowel movement have been weird and POIS has effected it. Personally for me I think it is because the muscles become overactivated either smooth and skeletal. These hormones have short half-lives but these effected cells seem to have more receptors or prolong its effects well after it is gone. It has been a longggg time since i studied neurotransmission. If we had better diagnostic tools, this would be easier to pinpoint. I think the muscle relaxer is providing you that relief. Instead of all these stimulants, i suggest replacing it with exercise. Walking/jogging/sprints and light weight training but the whole body.
Yeah quantum, everything in moderation.
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Dizzy,i had the same simptoms after taking b1.
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What strength did you take of b1? High dose and low B1 gets processed differently in the body.
How long were you taking 150mg before going to 300mg? Do you take it once a day? Do you take any other supplements or medication?
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At the begining 150 mg ,then 300
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I got problems breathing. As in: I had to think about breathing, otherwise it felt like my body/brain just didn't do it automatically. Quite scary. At one point I was afraid to go to sleep. Fortunately, all turned out well, but I'm more careful with B1 now.
I've got this symptom as well and don't take B1. It only happens during hot weather conditions. Are you sure the B1 is responsible for this?
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@Muon
Yes, I'm pretty sure it was the B1. The reason I know is that B1 was having such good effect on me, that I really tried a number of times to start using it again, and every time I got the same effect on breathing (although I tried lower doses later, so the effect was milder).
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Really fantastic work here. Thanks so much for all your contributions, nanna1!
I'm interested in trying this out. I have Thorne's Stress B-Complex sitting in my cupboard, which seems to include many of the ingredients in nanna1's POIS Cascade stack:
* 25mg Pyridoxine HCI
* 200mcg folate (L-5-Methyltetrahydrofolate)
* 100mcg B12 (in the form of methylcobalamin)
And it includes some additional ingredients:
* Thiamin HCI (50mg)
* Riboflavin (28.6mg)
* Niacin (80mg)
* Biotin (70mcg)
* Pantothenic acid (250mg)
* Choline (14mg)
Would this be an acceptable substitute for the B vitamins in the POIS cascade stack?
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Hi CuriousCharacter,
Thanks for the question! The B vitamins in your Stress B seem fine. I take low dose B vitamins daily, but I know there are many who take high dose B vitamins as a prepack. My B6 dose is low (2mg), which helps prevent tolerance. However, my original stack contained higher thiamine (vitamin B1) and higher choline than what is in your Stress B. I assume you will be using other sources of choline to increase your methyl-donors. If you choose to take this Stress-B as a prepack (taken before orgasm), then you may have to increase B1. But everybody's body is different, so I'm sure with a little experimentation you can find the right balance for you. Nurse86 wrote about a modified stack using vitamin B1 (https://poiscenter.com/forums/index.php?topic=2502.msg24761#msg24761).
I don't know what effect Riboflavin, Niacin, Biotin, Pantothenic acid will have, but there is a niacin thread here (http://poiscenter.com/forums/index.php?topic=235.msg2958#msg2958) and here (http://poiscenter.com/forums/index.php?topic=2525.msg21809#msg21809).
Thanks again and keep us updated. :)
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Have anybody felt hight temperature after taking CLA?
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Hi CuriousCharacter,
Thanks for the question! The B vitamins in your Stress B seem fine. I take low dose B vitamins daily, but I know there are many who take high dose B vitamins as a prepack. My B6 dose is low (2mg), which helps prevent tolerance. However, my original stack contained higher thiamine (vitamin B1) and higher choline than what is in your Stress B. I assume you will be using other sources of choline to increase your methyl-donors. If you choose to take this Stress-B as a prepack (taken before orgasm), then you may have to increase B1. But everybody's body is different, so I'm sure with a little experimentation you can find the right balance for you. Nurse86 wrote about a modified stack using vitamin B1 (https://poiscenter.com/forums/index.php?topic=2502.msg24761#msg24761).
I don't know what effect Riboflavin, Niacin, Biotin, Pantothenic acid will have, but there is a niacin thread here (http://poiscenter.com/forums/index.php?topic=235.msg2958#msg2958) and here (http://poiscenter.com/forums/index.php?topic=2525.msg21809#msg21809).
Thanks again and keep us updated. :)
Funny you should mention tolerance, Nanna. I'm currently taking your POIS Cascade Stack (though I haven't had time to test it out), and my biggest fear is developing a tolerance over time. How long have you been able to take it without upping the dose?
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Hi Bombardier,
For B vitamins, as long as you stay below the daily recommended dose, there is no tolerance. My folate (200mcg) and B6 (2mg) doses are below the daily recommended doses. My B1 and B12 doses are above the daily recommended dose (1mg, 2.5mcg respectively). So there are times when I throttle/cycle them. Usually, when I start taking B12 I will have dreams which is probably from increased neurotransmitter production. After a two or three days the dreams go away. If you have dreams or increased energy from taking B12 then you probably have less than optimum levels (or deficiency). At optimum levels there should not be any increase benefit to increasing the dose. Most people who eat meat 3 times a day will get the daily recommended B12 (2.5mcg). Since my diet on this stack is vegan, I don't get any B12 or D3 from food. So I have to supplement those vitamins.
There is no tolerance to taking omega-3. Your brain and heart are the main consumers of DHA and EPA and will always consume any excess omega-3. There is no tolerance to excess CLA, but there can be side effects related to too much fat breakdown. I personally have not experienced these side effect.
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Hey nanna1,
I am a heavy undermethylater. I have bad undermethylation and took the tests suggested in walsh's protocal. I have extremely high histamine and low in zinc and the protocol I am on now which is zinc 50 mg, p5p 100mg, Sam-e 600mg , vitamin e (400mg), and a couple other supplements. I tried your protocol but I didn't seem to have too much effect (I don't know if i had enough fish oil or alpha gpc). Whenever I have an 0 i get extreme racing heart beat, my throat gets really itchy, flu like symptoms, nausea, etc. I am on a low dose antidepressant and take 15mg of valium and want to get off it but I can't seem to figure out how to stop this.
I can stop 0 for a couple weeks and have a couple without symptoms but then it just keeps coming back. I am always tired and can sleep 12-14 hours a day if I could. There has to be someway to get rid of this. I have tried so many supplements and have wasted thousands on doctors.
Supplements I have tried:
L tryptophan - helps only at extremely high doses
l tryrosine
5 htp
almost all of your protocol
adrenal extracts like adrenal fatigue fighter
Ashwaganda
Vitamin c(helps)
niacin (sometimes can help)
and so much more.
your are really smart and I read some of your posts can we talk and have a chat?
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Have anybody felt hight temperature after taking CLA?
Hi Rinat,
I personally don't experience a high body temperature from taking CLA alone. When I exercise or do some physical activity like running up stares I do seem to experience a longer increase in body temperature than when I do not take it. I know exercise is suppose to increase body temperature, but usually I cool down pretty fast once I come to rest. My subjective opinion is that CLA can either prolong the increase in body temperature that I would normally experience from exercise, or it causes me to feel less tired so that I exercise longer/harder and burn more calories. This has happen to me sometimes when I drink caffeine beverages. Caffeine makes me feel less tired so I end up doing more work and exercising longer, but CLA does not have the stimulant effect that caffeine has. Either way, I have not measured my body temp while on CLA and compared to not being on CLA. So this is just a subjective opinion. But I can say that apart from activities that consume calories, I have not noticed any CLA effect on my body temperature (increase or decrease). I hope this useful in some way.
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Nanna,thank you for your answer)
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Hi HelpWithPois,
Thanks for your question. The racing heartbeat is probably due histamine or noradrenaline (norepinephrine (https://en.wikipedia.org/wiki/Norepinephrine)). Both of these produce a fight-or-flight response. It may be that your elevated histamine is due to an allergy. Have you tried getting a skin prick allergy test from doctor/allergist? If you have a skin prick test then you can identify allergens that may be causing your elevated histamine levels, like pet fur or mold.
(https://www.naughtylittlemastcells.com/wp-content/uploads/2017/12/MCAS-Triggers-Infographic.png)
Image from https://www.naughtylittlemastcells.com/infographics/
Intermittent Fasting (caloric restriction) has been proven to reduce the number of histamine releasing immune (mast, basophil, macrophage,...) cells in the body, increase natural T killer cells, and reduce allergen senstivity (Ref, Ref2 (https://www.linkedin.com/pulse/simplest-diet-seems-cure-cancers-alleviate-autoimmune-macarena-fritz)). Fasting has even been shown to eliminate some autoimmune diseases. If you don't like fasting you can try a commercial fast-mimicking-diet (FMD) like Prolon (https://prolonfmd.com/). Prolon is a commercial product developed at the University of Southern California and funded by the Nation Institute of Health (NIH). So it is based on real science and clinical trials(Refs (https://prolonfmd.com/science-research/)). I think that FMD are the best diets for POIS.
(https://i.imgur.com/VfMdGnH.jpg)
Figure 2 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862044/figure/F2/) from "Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence". This figure shows one case where a caloric-restriction or fast-mimicking-diet (FMD) resets the immune system and heals damage done by immune inflammation. Here is more information on how to do a FMD (Five day FMD (https://www.washingtonpost.com/video/lifestyle/food/how-the-new-five-day-fasting-diet-works/2015/06/22/70e3e66c-1908-11e5-bed8-1093ee58dad0_video.html?utm_term=.3e03f448316f)).
Sublingual vitamin D3 (https://www.amazon.com/NOW-Vitamin-Liposomal-Spray-2-Ounce/dp/B0045MJNCU/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1531365035&sr=1-4&keywords=vitamin+d3+k2+spray&dpID=41iFg2gwtWL&preST=_SY300_QL70_&dpSrc=srch), thiamine B1 and insulin are all negative regulators of histamine levels and the H1-hitamine receptor (diabetics have high histamine levels). In my opinion, sublingual vitamin D3 is a must for any stack because D3 is one of the bodies natural hormone regulators of the immune system. A vitamin D deficiency leads to chronic inflammation (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769) and allergies in everyone. Sublingual D3 is more bio-available than the pills. The pill form of D3 was not as effective for me.
Even if elevated histamine levels are caused by something other than POIS, this histamine can still make your POIS problems worse by stimulating the H1-histamine receptor. (1)Diet, (2)adequate sleep, (3)drinking water and (4)vitamin D levels are more important than stacking supplements. But once those 4 things are taken care of, then supplements can offer benefit.
TMG (betaine) is a good methyl donor if you want to save money from buying alpha-GPC. Herbal based supplements like (ashwaganda, tumeric, quercetin) can be helpful, but they do not work as prepacks because their bioavailability is too low (see Cost effective alternatives for omega-3 (http://poiscenter.com/forums/index.php?topic=2597.0)). The only effect that herbs (and flavonoids) have in the short-term is hormonal (they stimulate progesterone, estrogen and testosterone receptors (http://poiscenter.com/forums/index.php?topic=2502.msg21751;topicseen#msg21751)). To get the full benefit from herbal supplements, you have to take them daily to allow them to build up to therapeutic levels. Also, Curcumin is a MAO inhibitor which may interact with your antidepressant medications. I get my curcumin and quercetin from my diet (food only), which has been shown to have higher bioavailability and lower toxicity than the commercial pills. Adequate sleep is needed to strengthen the immune system so that it can fight whatever is causing POIS. Vitamin C (2g taken twice daily) can also strengthen the immune system and lower histamine levels (Ref (https://www.ncbi.nlm.nih.gov/pubmed/25095772)).
From what I can tell COX inhibitors are the most successful drugs to prevent POIS symptoms, but they each have their side-effect. Indomethacin (50mg) or aspirin (500mg) should be taken about 90 minutes before the start of sexual activity (see Betaherpesvirinae stack and vasoconstrictor notes in the original post (http://poiscenter.com/forums/index.php?topic=2502.0)). Celebrex (celecoxib) does not have the pharmakinetics to be taken as a prepack. Celecoxib has to be taken at 200mg twice a day with food for at least 5 days before you will see any noticable anti-inflammatory effect from it. So celecoxib is a long-term medication with no short-term benefits. With that said, celecoxib is the safest COX inhibitor that you can buy. I don't take pharmaceutical drugs. But for those that don't want to stick to a diet, several POISers find (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773) that COX inhibitors are an effective alternative for reducing POIS symptoms.
I know I crammed a lot of information in this post, but I hope some of this is helpful.
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nanna1, cool graphics!!
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From what I can tell COX inhibitors are the most successful drugs to prevent POIS symptoms, but they each have their side-effect. Indomethacin (50mg) or aspirin (500mg) should be taken about 90 minutes before the start of sexual activity (see Betaherpesvirinae stack and vasoconstrictor notes in the original post (http://poiscenter.com/forums/index.php?topic=2502.0)). Celebrex (celecoxib) does not have the pharmakinetics to be taken as a prepack. Celecoxib has to be taken at 200mg twice a day with food for at least 5 days before you will see any noticable anti-inflammatory effect from it. So celecoxib is a long-term medication with no short-term benefits. With that said, celecoxib is the safest COX inhibitor that you can buy. I don't take pharmaceutical drugs. But for those that don't want to stick to a diet, several POISers find (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773) that COX inhibitors are an effective alternative for reducing POIS symptoms.
I also think Piroxicam is an underappreciated COX inhibitor that mildly helps with brain symptoms but could be great if combined with other COX inhibitors.
Also from my experience it is important to take COX inhibitors before sexual activities, because taking them after ejaculation does almost nothing. Any possible explanation for that Nanna?
Also COX inhibitors and NSAID in general seem to be tested by many people but no one confirms their effect, especially Ibuprofen, I wonder why? Maybe it's a case where one COX inhibitor is not enough, especially for brain symptoms?
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Hi Nas,
Thank you for your question.
From what I can tell COX inhibitors are the most successful drugs to prevent POIS symptoms, but they each have their side-effect. Indomethacin (50mg) or aspirin (500mg) should be taken about 90 minutes before the start of sexual activity (see Betaherpesvirinae stack and vasoconstrictor notes in the original post (http://poiscenter.com/forums/index.php?topic=2502.0)). Celebrex (celecoxib) does not have the pharmakinetics to be taken as a prepack. Celecoxib has to be taken at 200mg twice a day with food for at least 5 days before you will see any noticable anti-inflammatory effect from it. So celecoxib is a long-term medication with no short-term benefits. With that said, celecoxib is the safest COX inhibitor that you can buy. I don't take pharmaceutical drugs. But for those that don't want to stick to a diet, several POISers find (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773) that COX inhibitors are an effective alternative for reducing POIS symptoms.
I also think Piroxicam is an underappreciated COX inhibitor that mildly helps with brain symptoms but could be great if combined with other COX inhibitors....Also COX inhibitors and NSAID in general seem to be tested by many people but no one confirms their effect, especially Ibuprofen, I wonder why? Maybe it's a case where one COX inhibitor is not enough, especially for brain symptoms?
Many POISers have confirmed the effectiveness of COX inhibitors. We have to remember that not all COX inhibitors are the same. The pharmacokinetics and potency (IC50) are different for each COX inhibitor. Some inhibit COX-1 or COX-2 or both. An explaination of what the potency measure IC50 means can be found here (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561). Smaller IC50 values result in a stronger effect (stronger COX inhibition). For example, indomethacin is a stronger COX-1 and COX-2 inhibitor than aspirin.
(https://i.imgur.com/T0oUg8G.png)
----------------
(https://i.imgur.com/PEmdWFT.png)
Ibuprofen is not an anti-inflammatory drug because it has extremely low potency. According to the above chart, Ibuprofen is the least effective COX inhibitor there is, because it does not inhibit COX-1 or COX-2 efficiently. I explain this in more details here (http://poiscenter.com/forums/index.php?topic=2597.msg22750;topicseen#msg22750).
One more thing to consider is the pharmacokinetics. Taking indomethacin 30 minutes before orgasm will likely not be as effective since it requires more than an 2 hours to reach peak blood levels (post (http://poiscenter.com/forums/index.php?topic=2683.msg24664;topicseen#msg24664)). A person that takes indomethacin 30 minutes before orgasm may not experience any relief. Whereas a person that takes indomethacin 120 minutes (2 hours) before orgasm will likely experience significant relief. Also since indomethacin has a half-life of about 4 hours, taking this drug more than 6 hours before an orgasm may not produce the expected relief either. So there is a window of time to start dosing between 2 hours and 4 hours pre-orgasm where you can expect relief.
For celebrex (celecoxib), you have to take it for at least 5 days consistent at the proper dose to see any effect. And it mainly inhibits COX-2. So not all COX inhibitors can be grouped together as being the same. They are very different in their dose timing and effects.
Also from my experience it is important to take COX inhibitors before sexual activities, because taking them after ejaculation does almost nothing. Any possible explanation for that Nanna?
The reason that COX inhibitors have to be taken before orgasm is explained by the below diagram (a testable hypothesis):
(https://i.imgur.com/cpuXuGZ.png)
Certain prostaglandins (i.e. PGE2) trigger events leading to POIS. COX inhibitors prevent prostaglandin production. But if you wait until after prostaglandins are produced, then COX inhibitors will have no effect. More details about the diagram can be found in the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). Other supplements/drugs work synergistically with COX-2 inhibitors by downregulating or blocking NF-kB (see Betaherpesvirinae stack (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)). Let me know if this was clear or if there is anything I need to correct.
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Hi Nas,
Thank you for your question.
From what I can tell COX inhibitors are the most successful drugs to prevent POIS symptoms, but they each have their side-effect. Indomethacin (50mg) or aspirin (500mg) should be taken about 90 minutes before the start of sexual activity (see Betaherpesvirinae stack and vasoconstrictor notes in the original post (http://poiscenter.com/forums/index.php?topic=2502.0)). Celebrex (celecoxib) does not have the pharmakinetics to be taken as a prepack. Celecoxib has to be taken at 200mg twice a day with food for at least 5 days before you will see any noticable anti-inflammatory effect from it. So celecoxib is a long-term medication with no short-term benefits. With that said, celecoxib is the safest COX inhibitor that you can buy. I don't take pharmaceutical drugs. But for those that don't want to stick to a diet, several POISers find (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773) that COX inhibitors are an effective alternative for reducing POIS symptoms.
I also think Piroxicam is an underappreciated COX inhibitor that mildly helps with brain symptoms but could be great if combined with other COX inhibitors....Also COX inhibitors and NSAID in general seem to be tested by many people but no one confirms their effect, especially Ibuprofen, I wonder why? Maybe it's a case where one COX inhibitor is not enough, especially for brain symptoms?
Many POISers have confirmed the effectiveness of COX inhibitors. We have to remember that not all COX inhibitors are the same. The pharmacokinetics and potency (IC50) are different for each COX inhibitor. Some inhibit COX-1 or COX-2 or both. An explaination of what the potency measure IC50 means can be found here (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561). Smaller IC50 values result in a stronger effect (stronger COX inhibition). For example, indomethacin is a stronger COX-1 and COX-2 inhibitor than aspirin.
(https://i.imgur.com/T0oUg8G.png)
Ibuprofen is not an anti-inflammatory drug because it has extremely low potency. According to the above chart, Ibuprofen is the least effective COX inhibitor there is, because it does not inhibit COX-1 or COX-2 efficiently. I explain this in more details here (http://poiscenter.com/forums/index.php?topic=2597.msg22750;topicseen#msg22750).
One more thing to consider is the pharmacokinetics. Taking indomethacin 30 minutes before orgasm will likely not be as effective since it requires more than an 2 hours to reach peak blood levels. A person that takes indomethacin 30 minutes before orgasm may not experience any relief. Whereas a person that takes indomethacin 120 minutes (2 hours) before orgasm will likely experience significant relief. Also since indomethacin has a half-life of about 4 hours, taking this drug more than 6 hours before an orgasm may not produce the expected relief either. So there is a window of time to start dosing between 2 hours and 4 hours pre-orgasm where you can expect relief.
For celebrex (celecoxib), you have to take it for at least 5 days consistent at the proper dose to see any effect. And it mainly inhibits COX-2. So not all COX inhibitors can be grouped together as being the same. They are very different in their dose timing and effects.
Also from my experience it is important to take COX inhibitors before sexual activities, because taking them after ejaculation does almost nothing. Any possible explanation for that Nanna?
The reason that COX inhibitors have to be taken before orgasm is explained by the below diagram (a testable hypothesis):
(https://i.imgur.com/cpuXuGZ.png)
Certain prostaglandins (i.e. PGE2) trigger events leading to POIS. COX inhibitors prevent prostaglandin production. But if you wait until after prostaglandins are produced, then COX inhibitors will have no effect. More details about the diagram can be found in the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). Other supplements/drugs work synergistically with COX-2 inhibitors by downregulating or blocking NF-kB (see Betaherpesvirinae stack (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)). Let me know if this was clear or if there is anything I need to correct.
Thank you very much Nanna!, that was incredibly helpful!
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Hey nanna1,
It comes back to the fact that I don't know what is causing the pois. My doctor who specializes in methlyation says i am a very bad undermethylater due to high histamine, low b-6, and other factors.. right now I take a low dose antidepressant, valium, sam-e (800mg), p5p (100 mg), zinc (50mg), and some l tryptophan. I have tried everything in the game including your stack (without the alpha gpc and still have pois).I can o max 2 times a week anything after that I can flu symptoms, runny nose, sore throat, anxiety, brain fog, fatigue, and I sleep 16 hours a day I am pretty much done at that point. How can I figure out to 0 without getting these symptoms I don't know what to do. I have spent probably over 15k on doctors and supplements and they can't fully help. Can I contact you or reach you at a specific email or number?
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I like your Pois schema very much, nanna1.
It must be keeped in a sticky thread.
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Hi Everyone
Since I have been very careful about the issue of my posture, I have had no pain in my spine for several weeks. But the other day I had a headache and had to take a painkiller called Neosaldine (dipyrone, isometepteno mucate, caffeine). One tablet was enough and I did not have to take another. One day after taking this painkiller I did masturbation 2 times the same day (1 pm and 7 pm). I had no POIS symptom. This had not happened to me for a long time. As I have always mentioned if I have my spine healthy and pain free, I have practically no symptoms but this time I had no symptoms. I felt as if I had not had an orgasm. I had no muscle tension, no fatigue, nothing! It may have been the effect of the painkiller the day before that was still working on my body. Possibly by blocking the action of prostaglandins.
It is not the cure, but have no symptons is very interesting. Maybe if we balance the things (colateral effects, happiness, etc..), may be interesting to have a tablet the day before orgasm if we can have nothing happening with our body after the orgasm. We can try to do things in a moderate way so that you can have orgasms at one time or another.
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Unfortunately, after about three weeks of diligent supplementation, I must report that the POIS Cascade Stack was ineffective for my type of POIS. I took all recommended supplements at their recommended doses, hoping it'd give me a sort of "safety net" against nocturnal emissions. When I had one however, I found myself in the midst of a very normal POIS Episode. The stack might have helped a bit with my emotional state that day, though one could also attribute that to an extra cup of coffee and interacting with friends.
I'll continue taking supplements till I've exhausted my current supply. Furthermore I am encouraged by the efficacy of caffeine in mitigating some of my symptoms, and have also gained some minor relief from a healthier diet and Vitamin C supplementation. As such, I may try the targeted herpes virus stack you detailed sometime down the line.
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Unfortunately, after about three weeks of diligent supplementation, I must report that the POIS Cascade Stack was ineffective for my type of POIS. I took all recommended supplements at their recommended doses, hoping it'd give me a sort of "safety net" against nocturnal emissions. When I had one however, I found myself in the midst of a very normal POIS Episode. The stack might have helped a bit with my emotional state that day, though one could also attribute that to an extra cup of coffee and interacting with friends.
I'll continue taking supplements till I've exhausted my current supply. Furthermore I am encouraged by the efficacy of caffeine in mitigating some of my symptoms, and have also gained some minor relief from a healthier diet and Vitamin C supplementation. As such, I may try the targeted herpes virus stack you detailed sometime down the line.
Did you also go vegan.
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Unfortunately, after about three weeks of diligent supplementation, I must report that the POIS Cascade Stack was ineffective for my type of POIS. I took all recommended supplements at their recommended doses, hoping it'd give me a sort of "safety net" against nocturnal emissions. When I had one however, I found myself in the midst of a very normal POIS Episode. The stack might have helped a bit with my emotional state that day, though one could also attribute that to an extra cup of coffee and interacting with friends.
I'll continue taking supplements till I've exhausted my current supply. Furthermore I am encouraged by the efficacy of caffeine in mitigating some of my symptoms, and have also gained some minor relief from a healthier diet and Vitamin C supplementation. As such, I may try the targeted herpes virus stack you detailed sometime down the line.
Did you also go vegan.
Can't say I went full-vegan, but I did adopt a much healthier diet. But, like, I'd expect to eke out at least a little benefit from that. Regardless, I'll have time to try again in the future.
I've found fair-to-decent results with niacin and Benadryl, such that a climax on niacin while in POIS instantly gave me 50% relief. I'll be investigating further when I have a chance.
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Hi Everyone
Since I have been very careful about the issue of my posture, I have had no pain in my spine for several weeks. But the other day I had a headache and had to take a painkiller called Neosaldine (dipyrone, isometepteno mucate, caffeine). One tablet was enough and I did not have to take another. One day after taking this painkiller I did masturbation 2 times the same day (1 pm and 7 pm). I had no POIS symptom. This had not happened to me for a long time. As I have always mentioned if I have my spine healthy and pain free, I have practically no symptoms but this time I had no symptoms. I felt as if I had not had an orgasm. I had no muscle tension, no fatigue, nothing! It may have been the effect of the painkiller the day before that was still working on my body. Possibly by blocking the action of prostaglandins.
It is not the cure, but have no symptons is very interesting. Maybe if we balance the things (colateral effects, happiness, etc..), may be interesting to have a tablet the day before orgasm if we can have nothing happening with our body after the orgasm. We can try to do things in a moderate way so that you can have orgasms at one time or another.
When will I ever have this experience :/
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Hi All,
Would appreciate some advice on supplements to help get rid of POIS symptom.
Abit of background, my nose tends to be super sensitive causing non stop sneezing and flu after masturbation (edging). If I ejaculate, my symptom tend to be worse and I find that taking antihistamine does help a little.
Read through a few articles via different sources and I believe I am currently in the group of undermethylated and taking Sam-E might help. I also have an autoimmune disorder with low blood platelets so I would like to avoid taking turmeric which tends to cause blood thinning.
My questions are as follow:
1. Is it OK to take SAM-E as a standalone supplement or should I be taking it with other forms of vitamin? (I'm currently taking multivitamin-which has the necessary vitamin b, zinc), standalone vitamin c and zinc for immunity and occasionally additional vitamin b complex - once every 3 or 4 days since I have it in my multivitamins)
2. How long do you guys continuously take Sam-e? Do I need to continuously take the supplements till I have no more further symptoms?
Any other advice is much appreciated for my flu and sensitive nose problem after orgasm. Brain fog tend to be minor but heal up fast within a day or two. I tend to have a very sensitive nose since young which cause alot of problems when exposed to dust.
Thank you!
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Can't say I went full-vegan, but I did adopt a much healthier diet. But, like, I'd expect to eke out at least a little benefit from that. Regardless, I'll have time to try again in the future.
Hi Bombadier,
It is great that you are eating healthier and feeling better. Good health is always positive. There are some aspects of the vegan diet that I did not fully appreciate when I first wrote the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). I knew that eating vegan made me feel better, but I didn't always connect it with the my understanding of how the POIS Cascade stack worked. I think now I can explain a little better why going full-vegan is important.
Part of the goal in the POIS Cascade Stack is to replace arachidonic acid (AA) with other omega fatty acids that do not produce inflammatory (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769) prostaglandins like PGE2. The reason for eating a vegan diet is that plants do not produce arachidonic acid (AA). Eicosanoids (https://en.wikipedia.org/wiki/Eicosanoid) are a group of mostly inflammatory molecules (like prostaglandin PGE2 and Leukotriene LTB4) produced from the arachidonic acid cascade when AA is oxidized by COX or LOX enzymes. In the study Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864), they show that omega-3 fatty acids like EPA can only reduce inflammatory prostaglandins from the AA cascade when dietary AA consumption from food is eliminated. They tested 4 groups of animals, (1)the control group (OA) with a normal healthy diet, (2)a group fed a high-AA/low-EPA diet (AA), (3)a group fed a low-AA/high-EPA diet (EPA), (4)a group fed an equal amount of AA and EPA (AA+EPA). The total eicosanoids produced from the AA cascade are summed (pooled) in the below chart.
(https://i.imgur.com/BLOEits.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
This (AA+EPA) result shows that it does not matter how healthy a diet seems to be. If the amount of AA in the diet is significant, then omega-3 supplementation has very little effect on reducing AA and its effects in the body. Other studies testing AA+DHA show similar results. This is because cell walls in the body have a preference to store AA over omega-3s. I'm still not sure how CLA works, but it seems to modify the body's composition of other omega fatty acids (shifting the type of fat that the body stores).
A more detailed look at the data shows that a low-AA/high-EPA diet (EPA) not only reduces inflammatory molecules (PGE2, PGF2a, LTB4, LTE4), but it also boost the relatively anti-inflammatory molecule LTE5.
(https://i.imgur.com/LMLR959.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
"Dietary AA is almost exclusively associated with animal products." (Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864))
The omega-6 arachidonic acid is only produced naturally in animal fat. The below table shows some of the foods with the highest AA content.
(https://i.imgur.com/wLrTlG9.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
This means that removing AA from your diet will probably mean removing all sources of animal fat from your diet (vegan diet). If you are not on a low-AA diet, I don't see any advantage to taking omega-3 supplements. Only when you are on a low-AA (vegan) diet should you expect benefits from the omega-3s in the POIS Cascade stack.
It is important to note that most inflammatory molecules (i.e. cytokines, histamine, etc...) rely upon the arachidonic acid cascade to cause inflammation. If the AA cascade is blocked, molecules like histamine and IL-8 cannot produce inflammation or inflammatory diseases. Vegan diets are typically low in vitamin D3, vitamin B12 and creatine. But a vegan diet supplemented with vitamin D3, B12 and a methyl-donor (betaine TMG) should in-principle reduce inflammation throughout the body and produce better health. My medical test (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039) show that my recent markers for inflammation are low (9. platelet counts, 9. sedimentation rate, 10. cholesterol, 12. homocysteine, 13. tryptase). Also, I rarely get DOMS (https://en.wikipedia.org/wiki/Delayed_onset_muscle_soreness) from exercise any more. Maybe that means something or maybe it doesn't. In any case, I'm sorry for the confusion on my part. I did not always understand how important this type of diet was to my results. But I hope this clarifies the significance of the vegan diet in this stack.
-----------------------------------------
For those that cannot eat vegan, an alternative way of reducing prostaglandins and inflammation is to take COX and NF-kappaB inhibitors. For example, taking one (only one) of the follow COX inhibitors:
--Aspirin (500mg, 90 minutes pre-activity)
--Indomethacin (50mg, 2 hours pre-activity, with food, 4.5-hour half-life)
--Naproxen (500mg, 3 hours pre-activity, with food, 8-hour half-life)
and some of the following NF-kappaB inhibitors:
--vitamin D3 (2000-4000 IU daily, sublingual)
--caffeine (65-100mg, 90 minutes pre-activity)
--Tylenol/Paracetamol/acetaminophen (250-500mg, 95 - 115 minutes pre-activity)
--selenium/selenomethione (100-200 mcg daily, dosage depends on the amount of selenium from diet)
Flavonoids like luteolin, quercetin and curcumin can also downregulate NF-kB and inhibit COX, but only when they are consumed daily over time through food, teas and/or supplements (see post1 (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561), post2 (http://poiscenter.com/forums/index.php?topic=2597.msg22594#msg22594)).
All COX inhibitors have vasoconstriction properties since most protaglandins (like PGE2) are vasodilators. Caffeine and paracetamol are also vasoconstrictors (see Betaherpesvirinae stack and About Vasoconstrictors notes (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)). Naproxen has an 8-hour half-life and can help reduce nocturnal emission (NE) induced POIS when taken before bed-time. However, naproxen has more side-effects than aspirin or indomethacin when taken daily over several months. Some anti-histamine medications such as Benadryl (diphenhydramine) and Claritin (loratadine) are associated with long-term memory loss and cognitive decline (see post (http://poiscenter.com/forums/index.php?topic=2502.msg21708;topicseen#msg21708)). Zyrtec/Xyzal (cetirizine/levocetirizine) and Allegra (fexofenadine) are not associated with cognitive decline. Consult with your physician or medical care professional before taking pharmaceutical drugs. Make sure these do not interact with your current medications.
Ref1: "Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo (https://www.ncbi.nlm.nih.gov/pubmed/7852864)" (1994)
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Hi Nanna,
Can you please respond to my second post above?
Best,
Derek
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Hi Nanna1
"omega-3 fatty acids like EPA can only reduce inflammatory prostaglandins from the AA cascade when dietary AA consumption from food is eliminated"
But most fishes contain both aa and omega 3. So eating fish should not provide any inflammation reducing effect isn't it.
https://www.livestrong.com/article/38903-foods-high-arachidonic-acid/
But fish finds a prominent place is most of inflammation reducing diets. How this happens? Any idea
https://www.bustle.com/p/14-foods-that-reduce-inflammation-which-you-didnt-know-8870860
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Hi!
I will go through this you have written carefully, it is in line with what I think is wrong with me. I am a woman. I don't pretend to understand much of what you have written, however, I have noticed this:
After orgasm I become "ugly" - a sharper face sort of thing, but not in a good way
If I eat a lot of meat and very little fat, same thing happens. I look better when I eat more easy carbs, but I don't tolerate carbs very well for IBS reasons. When I eat carbs and don't play with myself my face is more rounded. I have seen the same kind of features on other women with very low cortisol. I get the same kind of ugly face from coffee or other foods that affect the adrenals.
Men can supposedly, maybe, see if a woman masturbates a lot and they are more attracted to those who masturbates a lot. (This is from some of this bad research, you know: fifteen college kids look at photos, so I can't be bothered to find reference.)
Anyway, meat contains also arachidonic acid.
Interested to hear if you think there could be a connection.
I am thinking that if I figure out this problem I have, then also my general chronic fatigue might improve.
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Hi Allwomansarepreety, it is intresting that you mention facial change after sex or masturbation(my awatar) it is wel known that some poisers hawe "mad _zombee" facilall change(couse could be hi adrenals).
About meat diaet, i dont know , ebiybary is diferent, i folow my logic and comon sense, managing AA cascade culd mybe help for some of as BUT...(99% procent people eat meat 24/7 in my country, non of them probbly hawe pois and wery les procent of inflamatory desees).
I like nana , he is smart guy, BUT i dont think that AA is root couse of our problem, simply evidence is guys on GLC(goinglescrazy) tread whos are complitly cured pois by foloving Aip , paleo, hi fat an meats low carbs diets etc diets.
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Can't say I went full-vegan, but I did adopt a much healthier diet. But, like, I'd expect to eke out at least a little benefit from that. Regardless, I'll have time to try again in the future.
Hi Bombadier,
It is great that you are eating healthier and feeling better. Good health is always positive. There are some aspects of the vegan diet that I did not fully appreciate when I first wrote the original post (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). I knew that eating vegan made me feel better, but I didn't always connect it with the my understanding of how the POIS Cascade stack worked. I think now I can explain a little better why going full-vegan is important.
Part of the goal in the POIS Cascade Stack is to replace arachidonic acid (AA) with other omega fatty acids that do not produce inflammatory (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769) prostaglandins like PGE2. The reason for eating a vegan diet is that plants do not produce arachidonic acid (AA). Eicosanoids (https://en.wikipedia.org/wiki/Eicosanoid) are a group of mostly inflammatory molecules (like prostaglandin PGE2 and Leukotriene LTB4) produced from the arachidonic acid cascade when AA is oxidized by COX or LOX enzymes. In the study Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864), they show that omega-3 fatty acids like EPA can only reduce inflammatory prostaglandins from the AA cascade when dietary AA consumption from food is eliminated. They tested 4 groups of animals, (1)the control group (OA) with a normal healthy diet, (2)a group fed a high-AA/low-EPA diet (AA), (3)a group fed a low-AA/high-EPA diet (EPA), (4)a group fed an equal amount of AA and EPA (AA+EPA). The total eicosanoids produced from the AA cascade are summed (pooled) in the below chart.
(https://i.imgur.com/BLOEits.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
This (AA+EPA) result shows that it does not matter how healthy a diet seems to be. If the amount of AA in the diet is significant, then omega-3 supplementation has very little effect on reducing AA and its effects in the body. Other studies testing AA+DHA show similar results. This is because cell walls in the body have a preference to store AA over omega-3s. I'm still not sure how CLA works, but it seems to modify the body's composition of other omega fatty acids (shifting the type of fat that the body stores).
A more detailed look at the data shows that a low-AA/high-EPA diet (EPA) not only reduces inflammatory molecules (PGE2, PGF2a, LTB4, LTE4), but it also boost the relatively anti-inflammatory molecule LTE5.
(https://i.imgur.com/LMLR959.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
"Dietary AA is almost exclusively associated with animal products." (Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864))
The omega-6 arachidonic acid is only produced naturally in animal fat. The below table shows some of the foods with the highest AA content.
(https://i.imgur.com/wLrTlG9.png)
Figure from Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/7852864).
This means that removing AA from your diet will probably mean removing all sources of animal fat from your diet (vegan diet). If you are not on a low-AA diet, I don't see any advantage to taking omega-3 supplements. Only when you are on a low-AA (vegan) diet should you expect benefits from the omega-3s in the POIS Cascade stack.
It is important to note that most inflammatory molecules (i.e. cytokines, histamine, etc...) rely upon the arachidonic acid cascade to cause inflammation. If the AA cascade is blocked, molecules like histamine and IL-8 cannot produce inflammation or inflammatory diseases. Vegan diets are typically low in vitamin D3, vitamin B12 and creatine. But a vegan diet supplemented with vitamin D3, B12 and a methyl-donor (betaine TMG) should in-principle reduce inflammation throughout the body and produce better health. My medical test (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039) show that my recent markers for inflammation are low (9. platelet counts, 9. sedimentation rate, 10. cholesterol, 12. homocysteine, 13. tryptase). Also, I rarely get DOMS (https://en.wikipedia.org/wiki/Delayed_onset_muscle_soreness) from exercise any more. Maybe that means something or maybe it doesn't. In any case, I'm sorry for the confusion on my part. I did not always understand how important this type of diet was to my results. But I hope this clarifies the significance of the vegan diet in this stack.
-----------------------------------------
For those that cannot eat vegan, an alternative way of reducing prostaglandins and inflammation is to take COX and NF-kappaB inhibitors. For example, taking one (only one) of the follow COX inhibitors:
--Aspirin (500mg, 90 minutes pre-activity)
--Indomethacin (50mg, 2 hours pre-activity, with food, 4.5-hour half-life)
--Naproxen (500mg, 3 hours pre-activity, with food, 8-hour half-life)
and some of the following NF-kappaB inhibitors:
--vitamin D3 (2000-4000 IU daily, sublingual)
--caffeine (65-100mg, 90 minutes pre-activity)
--Tylenol/Paracetamol/acetaminophen (250-500mg, 95 - 115 minutes pre-activity)
--selenium/selenomethione (100-200 mcg daily, dosage depends on the amount of selenium from diet)
Flavonoids like luteolin, quercetin and curcumin can also downregulate NF-kB and inhibit COX, but only when they are consumed daily over time through food, teas and/or supplements (see post1 (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561), post2 (http://poiscenter.com/forums/index.php?topic=2597.msg22594#msg22594)).
All COX inhibitors have vasoconstriction properties since most protaglandins (like PGE2) are vasodilators. Caffeine and paracetamol are also vasoconstrictors (see Betaherpesvirinae stack and About Vasoconstrictors notes (http://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497)). Naproxen has an 8-hour half-life and can help reduce nocturnal emission (NE) induced POIS when taken before bed-time. However, naproxen has more side-effects than aspirin or indomethacin when taken daily over several months. Some anti-histamine medications such as Benadryl (diphenhydramine) and Claritin (loratadine) are associated with long-term memory loss and cognitive decline (see post (http://poiscenter.com/forums/index.php?topic=2502.msg21708;topicseen#msg21708)). Zyrtec/Xyzal (cetirizine/levocetirizine) and Allegra (fexofenadine) are not associated with cognitive decline. Consult with your physician or medical care professional before taking pharmaceutical drugs. Make sure these do not interact with your current medications.
Ref1: "Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo (https://www.ncbi.nlm.nih.gov/pubmed/7852864)" (1994)
Oof... You know Nanna, I think you might be onto something here. Over this weekend I'd accidentally adhered to a vegan diet (bread, cereal, vegetables, and hot sauce), and felt utterly spectacular. My thinking was quicker, I was much more articulate, and I generally felt the best I had in weeks. But then I took a risk and tried to treat myself to a pizza last night, and things have since become a bit difficult. I've read you have problems with cheese as well, so you can understand the sort of miniature POIS episode I'm going through right now.
I'll be returning to the special diet I mentioned, and adhering to it strictly henceforth. I'll also start taking supplements again. Thanks for all your help.
EDIT: Just wanting to give a quick update on my case. Unfortunately I'm one of those POISers who gets light-to-moderate symptoms from both eating and taking showers (hot or cold). However as I type this, I've just concluded almost a full week of eating vegan, and I can say with certainty that things have improved in my day-to-day life. I'm now more spry, more agile, and my mind is the clearest it's been in nearly a year. I still get headaches and general brain fog after eating, but these are much weaker than before. It is also worth noting that I had to stop supplementation of the POIS Cascade Stack due to health reasons, but will be returning to it soon.
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Hi Nanna,
Can you please respond to my second post above?
Best,
Derek
Hi Derek,
I try to avoid discussing the cause of POIS on this thread. For discussions about the root cause of POIS, I would refer you to the following post:
---Ideas on Herpes Induced POIS (https://poiscenter.com/forums/index.php?topic=2683.0)
---Gather and Post Here Your Medical Tests Results - Discussion Thread (https://poiscenter.com/forums/index.php?topic=2695.0)
Also, there may be an immune component to POIS (see https://poiscenter.com/forums/index.php?topic=2695.msg24966#msg24966). This still needs further validation to become a POIS biomarker.
Hi Nanna1
"omega-3 fatty acids like EPA can only reduce inflammatory prostaglandins from the AA cascade when dietary AA consumption from food is eliminated"
But most fishes contain both aa and omega 3. So eating fish should not provide any inflammation reducing effect isn't it.
https://www.livestrong.com/article/38903-foods-high-arachidonic-acid/
But fish finds a prominent place is most of inflammation reducing diets. How this happens? Any idea
https://www.bustle.com/p/14-foods-that-reduce-inflammation-which-you-didnt-know-8870860
Hi aswinpras06,
I'm sorry if what I have said before was confusing. Omega-3 fatty acids reduce inflammation, and usually omega-3 supplements are purified to increase the omega-3:omega-6 ratio or remove omega-6 entirely. One should always check the supplement label to make sure that omega-6 has been removed. But fish consumption does not reduce inflammation in any diet. There are no studies showing fish consumption reduces inflammation. When interpreting the result of these types of studies, it is important to consider that the control group is also meat eaters. The control group that scientist usually compare fish diets to are other meat (pork, beef, etc...) containing diets. Fish can increase CFS (link (https://nutritionfacts.org/2016/09/22/chronic-fatigue-syndrome-and-fish-food-poisoning/), video (https://nutritionfacts.org/video/ciguatera-poisoning-chronic-fatigue-syndrome/)) and reduce DNA telomere length (video (https://nutritionfacts.org/video/research-into-reversing-aging/)). Meaning that whole-fish consumption accelerates aging.
Fish is not less inflammatory than vegetables. Compared to a complete vegan diet, a similar fish containing diet will increase inflammation, disease (such as cancer) and aging (video (https://youtu.be/LpYwcTFVnv8?t=3m33s)). The Mediterranean diet (https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801) is a fish/chicken containing (low-meat/no-dairy) diet. The meat in the Mediterranean diet is only to supply protein and calories. The Mediterranean diet contains natural COX inhibitors from olive oil, oregano and thyme. It also contains large amounts of sulfur containing antioxidants like N-acetylcysteine from onions and garlic. The COX inhibitors and antioxidants in the Mediteranean diet help reduce the inflammatory effects of fish when the fish consumption is kept low.
In general, herbs and spices (tumeric, oregano, thyme, cinnamon, ginger, cumin) and high-sulfur containing vegetables (Allium (https://en.wikipedia.org/wiki/Allium) and cruciferous vegetables (https://en.wikipedia.org/wiki/Cruciferous_vegetables)) are the main anti-inflammatory components of diets. Many other fruits, vegetables and nuts can also reduce inflammation depending on how they are cooked and prepared. Meat, dairy and simple carbs are the main pro-inflammatory components of most diets. This video from Professor Katherine Richman at the UC San Diego Medical Center explains in detail the science behind what I described (Healthy Wealthy and Wise: Diet for Healthy Aging - Research on Aging (https://youtu.be/LpYwcTFVnv8?t=53m57s)). I tried to skip to the part of the video that discusses fish directly, but if you start from the begining of the video, this response will make more sense. I hope that clarifies things.
After orgasm I become "ugly" - a sharper face sort of thing, but not in a good way
If I eat a lot of meat and very little fat, same thing happens. I look better when I eat more easy carbs, but I don't tolerate carbs very well for IBS reasons. When I eat carbs and don't play with myself my face is more rounded. I have seen the same kind of features on other women with very low cortisol. I get the same kind of ugly face from coffee or other foods that affect the adrenals.
Hi ...SoPrettyWoman,
Inflammation in the body can cause swelling and/or irritation of the skin layers which shows physically. I'm not sure if this is what is going on in your case. You may be interesting in reading the responses of female POISers to see if you can relate to these (post: Women with Post Orgasmic Illness Syndrome (https://poiscenter.com/forums/index.php?topic=2755.msg24730#msg24730)). There may be some symptoms which are more common in women.
Men can supposedly, maybe, see if a woman masturbates a lot and they are more attracted to those who masturbates a lot. (This is from some of this bad research, you know: fifteen college kids look at photos, so I can't be bothered to find reference.)
Men are more attracted to happier women. So if masturbation makes a woman less depressed then she may appear more attractive.
Men are also more attracted to red (color) faces (red lips, red cheeks, red makeup, etc...). When women are aroused, blood rushes to their skin making it look redder due to vasodilation. During orgasm, the amount of blood flow to the skin can dramatically increase in some cases (sex flush (https://en.wikipedia.org/wiki/Flushing_(physiology)#Sex_flush)). The extra blood flow can also change the physical shape of the face as well. If women who masturbate often are also aroused more often, then this could be another reason why they appear more attractive.
People who are aroused, tend to have more dilated eye pupils. Men who see a woman with dilated eye pupils may find her more attractive (article (https://blogs.scientificamerican.com/guest-blog/learning-the-look-of-love-in-your-eyes-the-light-the-heat/)). Sorry I could not be of more help.
-
This is a long topic. I got 2 questions. Maybe the answer is somewhere here but it would take a lot of time to scroll down 24 pages.
1. Nanna, I bought the pills for your stack. But everytime I scared of how many pills I have to take beside the ones I am taking now (Fexofenadin, cefuroxim, amitriptyline, taurine, iron, vitamin D, cranberry pills, garlic pills). My question is: is it ok to mix your stack in 1 or 2 drinks?
2. Beside Nanna, is there someone else who finds relief of Nanna’s stack?
-
This is a long topic. I got 2 questions. Maybe the answer is somewhere here but it would take a lot of time to scroll down 24 pages.
1. Nanna, I bought the pills for your stack. But everytime I scared of how many pills I have to take beside the ones I am taking now (Fexofenadin, cefuroxim, amitriptyline, taurine, iron, vitamin D, cranberry pills, garlic pills). My question is: is it ok to mix your stack in 1 or 2 drinks?
2. Beside Nanna, is there someone else who finds relief of Nanna’s stack?
Which one is his current stack?
-
This is a long topic. I got 2 questions. Maybe the answer is somewhere here but it would take a lot of time to scroll down 24 pages.
1. Nanna, I bought the pills for your stack. But everytime I scared of how many pills I have to take beside the ones I am taking now (Fexofenadin, cefuroxim, amitriptyline, taurine, iron, vitamin D, cranberry pills, garlic pills). My question is: is it ok to mix your stack in 1 or 2 drinks?
2. Beside Nanna, is there someone else who finds relief of Nanna’s stack?
Which one is his current stack?
I bought this. Don’t know if it is the current stack:
SAM-e
Vit B6
Vit B11
Vit B12
Alpha-gpc
Vit B1
Omega 3 fish oil
Vit D3
-
This is a long topic. I got 2 questions. Maybe the answer is somewhere here but it would take a lot of time to scroll down 24 pages.
1. Nanna, I bought the pills for your stack. But everytime I scared of how many pills I have to take beside the ones I am taking now (Fexofenadin, cefuroxim, amitriptyline, taurine, iron, vitamin D, cranberry pills, garlic pills). My question is: is it ok to mix your stack in 1 or 2 drinks?
2. Beside Nanna, is there someone else who finds relief of Nanna’s stack?
Which one is his current stack?
I bought this. Don’t know if it is the current stack:
SAM-e
Vit B6
Vit B11
Vit B12
Alpha-gpc
Vit B1
Omega 3 fish oil
Vit D3
I tried everything there except for Alpha GPC and SAM-e and didn't have any success. Would like to try SAM-e, but here (M?xico) it's expensive and only available as a patent drug, not a supplement. Alpha GPC is also hard to get here.
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Scrub: Alpha-GPC should be no problem. Instead if you search for 'Lecithin' and preferably non-GMO Sunflower Lecithin. It is a potent source for choline as alpha-gpc is.
-
Hi,
I just want to report in that nanna1 POIS stack works for me. Bear in mind that I do have an issue with MTHFR where person cannot optimally process folate (B9). The supplements I started with is a brand Seeking Heath B12+L-5-MTHF which only has these 2 ingredients then I switched over to Thorne Methyl-Guard which adds the additional B6 and TMG. Plus SAMe Jarrows Forumulas. I also have Alpha-GPC which I have not tried yet but soon, more on this later due to a article I found.
https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/
"6) Be careful with SAMe. SAMe supplements support methylation, but MTHFR mutations increase the use of glycine to buffer SAMe levels, even when you don?t have enough. While I do not make a blanket recommendation against supplementing with SAMe, I caution against its use in this context because it could aggravate the loss of glycine. If you use it, be careful, and consider monitoring your glycine levels (see recommended lab tests below)."
If @nana1 can respond to this it will be great.
So my results are the following, I only took the supplements for 3 days and decided to O after one year of abstinence. First I watched porn to test the waters, usually watching porn for prolong of time I would usually feeling the symptoms coming up. After not feeling any adverse reaction I went a head and O on day 1. Nothing happens. Alright this is cool, I usually would get messed up and not function till after a week. Ok so then I would take this and see how far I can go. Day 2, I O 2x on the same day back to back, you heard me, this is like suicide in the POIS world. This would probably kill me considering the fact I O the day before. Nothing happens in terms of mental capacity besides feeling bit sleepy but to my surprise I function as normal. Day 3, I again try to push my luck. I O once again but this time took Excerdrin, after O I would feel tired but the caffeine kicked in and I feel great. That's going to conclude my multiple O test. I think I can safely say my POIS is cured and I can finally move on as a normal person.
On the physical aspect after an O,
1. My face looks like I aged several years.
2. My face would feel saggy or loose but after taking Excerdrin, my face feels nice and firm but I don't know which ingredients from Excerdrin caused this.
It seems to me that this stack only works with people who have MTHFR issues so therefore it will not work for everyone.
Thanks nana1.
-
Hi,
I just want to report in that nanna1 POIS stack works for me. Bear in mind that I do have an issue with MTHFR where person cannot optimally process folate (B9). The supplements I started with is a brand Seeking Heath B12+L-5-MTHF which only has these 2 ingredients then I switched over to Thorne Methyl-Guard which adds the additional B6 and TMG. Plus SAMe Jarrows Forumulas. I also have Alpha-GPC which I have not tried yet but soon, more on this later due to a article I found.
https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/
"6) Be careful with SAMe. SAMe supplements support methylation, but MTHFR mutations increase the use of glycine to buffer SAMe levels, even when you don?t have enough. While I do not make a blanket recommendation against supplementing with SAMe, I caution against its use in this context because it could aggravate the loss of glycine. If you use it, be careful, and consider monitoring your glycine levels (see recommended lab tests below)."
If @nana1 can respond to this it will be great.
So my results are the following, I only took the supplements for 3 days and decided to O after one year of abstinence. First I watched porn to test the waters, usually watching porn for prolong of time I would usually feeling the symptoms coming up. After not feeling any adverse reaction I went a head and O on day 1. Nothing happens. Alright this is cool, I usually would get messed up and not function till after a week. Ok so then I would take this and see how far I can go. Day 2, I O 2x on the same day back to back, you heard me, this is like suicide in the POIS world. This would probably kill me considering the fact I O the day before. Nothing happens in terms of mental capacity besides feeling bit sleepy but to my surprise I function as normal. Day 3, I again try to push my luck. I O once again but this time took Excerdrin, after O I would feel tired but the caffeine kicked in and I feel great. That's going to conclude my multiple O test. I think I can safely say my POIS is cured and I can finally move on as a normal person.
On the physical aspect after an O,
1. My face looks like I aged several years.
2. My face would feel saggy or loose but after taking Excerdrin, my face feels nice and firm but I don't know which ingredients from Excerdrin caused this.
It seems to me that this stack only works with people who have MTHFR issues so therefore it will not work for everyone.
Thanks nana1.
That’s great that it worked for you. The stack has changed. I thought that I did buy everything. But now I see some things I bought aren’t in the stack anymore. For example DHA fishoil.
To be sure you took this everything on his new list but only not the SAMe?
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---pyridoxine HCl, vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Folate, vitamin B9 (200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (>50mcg, sublingual) [methyl group cycler]
---Pick from one of the following three methyl group donors:
1. tri-methylglycine, betaine (1.5g) [methyl group donor]
2. alpha-glycerophosphocholine, alpha-GPC (1.2g) [methyl group donor]
3. phosphatidylcholine, Lecithin concentrate (1.5g) [methyl group donor] (take with food)
With food, twice daily (fat soluble):
---conjugated linoleic acid, CLA (2g) [NF-kB inhibitor and COX-2 downregulator]
---vitamin D3 (1000 IU) [NF-kB inhibitor and COX-2/IDO/TDO down-regulator]
Betaherpesvirinae stack:
Taken 90 minutes prior to sexual activity (prepack):
Vasoconstrictors:
---(Paracetamol 250mg, indomethacin 50mg, caffeine 65mg)
NF-kB/cytokine regulators:
---vitamin D3 (2000IU sublingual)
---Betaine-TMG (2g)
---N-acetylcysteine (1.2g)
---selenomethionine (100 micrograms)
-
That’s great that it worked for you. The stack has changed. I thought that I did buy everything. But now I see some things I bought aren’t in the stack anymore. For example DHA fishoil.
To be sure you took this everything on his new list but only not the SAMe?
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---pyridoxine HCl, vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Folate, vitamin B9 (200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (>50mcg, sublingual) [methyl group cycler]
---Pick from one of the following three methyl group donors:
1. tri-methylglycine, betaine (1.5g) [methyl group donor]
2. alpha-glycerophosphocholine, alpha-GPC (1.2g) [methyl group donor]
3. phosphatidylcholine, Lecithin concentrate (1.5g) [methyl group donor] (take with food)
With food, twice daily (fat soluble):
---conjugated linoleic acid, CLA (2g) [NF-kB inhibitor and COX-2 downregulator]
---vitamin D3 (1000 IU) [NF-kB inhibitor and COX-2/IDO/TDO down-regulator]
Betaherpesvirinae stack:
Taken 90 minutes prior to sexual activity (prepack):
Vasoconstrictors:
---(Paracetamol 250mg, indomethacin 50mg, caffeine 65mg)
NF-kB/cytokine regulators:
---vitamin D3 (2000IU sublingual)
---Betaine-TMG (2g)
---N-acetylcysteine (1.2g)
---selenomethionine (100 micrograms)
Hi Vandemolen,
I have not seen the old list so no but I still have not acquire all the supplements in this current nana1 stack. I take Thorne Methyl-Guard which contains B6, B9, B12 and TMG. Then SAMe from Jarrows. This already covers most of nana1 stack. Excerdrin from Betaherpesvirinae stack. Actually forgot to mention I also tried NAC but stopped taking cause I have issues with histamine.
The next supplements I would like to try would be CLA and Alpha-GPC.
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Ok so you took excerdrin instead of Paracetamol, indomethacin and caffeine? In The Netherlands you need a doctor’s prescription for indomethacin. But excerdrin is for sale.
-
Ok so you took excerdrin instead of Paracetamol, indomethacin and caffeine? In The Netherlands you need a doctor’s prescription for indomethacin. But excerdrin is for sale.
Yes, since I would need to buy different products for Paracetamol, indomethacin and caffeine.
1. Tylenol (Paracetamol)
2. Ibuprofen (Indomethacin)
3. Caffeine
All these are also available over the counter.
I just instead take Excerdrin which also includes Caffeine. This stack is strictly for PE.
-
Ok so you took excerdrin instead of Paracetamol, indomethacin and caffeine? In The Netherlands you need a doctor’s prescription for indomethacin. But excerdrin is for sale.
Yes, since I would need to buy different products for Paracetamol, indomethacin and caffeine.
1. Tylenol (Paracetamol)
2. Ibuprofen (Indomethacin)
3. Caffeine
All these are also available over the counter.
I just instead take Excerdrin which also includes Caffeine. This stack is strictly for PE.
Oh ok I don’t have PE or NE. So then I don’t have to take these 3 medicines?
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
-
Ok so you took excerdrin instead of Paracetamol, indomethacin and caffeine? In The Netherlands you need a doctor’s prescription for indomethacin. But excerdrin is for sale.
Yes, since I would need to buy different products for Paracetamol, indomethacin and caffeine.
1. Tylenol (Paracetamol)
2. Ibuprofen (Indomethacin)
3. Caffeine
All these are also available over the counter.
I just instead take Excerdrin which also includes Caffeine. This stack is strictly for PE.
Oh ok I don’t have PE or NE. So then I don’t have to take these 3 medicines?
If you don't have PE, it's not necessary to take Excerdrine although it might still benefit you if you know what I mean.
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
Ok, wish you the best of luck.
Btw, do you happen to know if you have MTHFR? I have not read the whole thread so I don't know if the stack can respond to people with non-mthfr issues.
Not sure about the interactions between the stack and zinc/cefuroxim.
-
Hi,
I just want to report in that nanna1 POIS stack works for me. Bear in mind that I do have an issue with MTHFR where person cannot optimally process folate (B9).
(...)
It seems to me that this stack only works with people who have MTHFR issues so therefore it will not work for everyone.
Thanks nana1.
Hi itsmel, and welcome to the forum ! :)
I tend to agree with your opinion that Nanna's stack works with people having a MTHFR issue, and not necessarily with others. That is the reason why I have placed in the "Methylation support" section of my POIS Types Chart ( http://poiscenter.com/forums/index.php?topic=2338.msg19448#msg19448)
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
Ok, wish you the best of luck.
Btw, do you happen to know if you have MTHFR? I have not read the whole thread so I don't know if the stack can respond to people with non-mthfr issues.
Not sure about the interactions between the stack and zinc/cefuroxim.
Thanks! I don’t think I have MTHFR. Never heard about it haha. I will google it to see what the symptoms are. Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
-
Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
According to what I've read, with a dysfunctional MTHFR gene you have to take the right form of folate, which is methylfolate.
Some people determine if they have MTHFR problems through a genetic test like offered by 23andme. However, this only tests a selected number of SNPs (=locations of the gene), so in theory your copies of the gene could be defective even if the test says they are not. On the other hand, if the test says you have defective MTHFR genes, then you can be sure that you have a problem there.
-
Hi itsmel, and welcome to the forum ! :)
I tend to agree with your opinion that Nanna's stack works with people having a MTHFR issue, and not necessarily with others. That is the reason why I have placed in the "Methylation support" section of my POIS Types Chart ( http://poiscenter.com/forums/index.php?topic=2338.msg19448#msg19448)
Thanks!
-
Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
According to what I've read, with a dysfunctional MTHFR gene you have to take the right form of folate, which is methylfolate.
Some people determine if they have MTHFR problems through a genetic test like offered by 23andme. However, this only tests a selected number of SNPs (=locations of the gene), so in theory your copies of the gene could be defective even if the test says they are not. On the other hand, if the test says you have defective MTHFR genes, then you can be sure that you have a problem there.
That's correct.
The simplest way to check for MTHFR issues is through 23andme testing service and then have it run through genetic genie.
http://geneticgenie.org/
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
Ok, wish you the best of luck.
Btw, do you happen to know if you have MTHFR? I have not read the whole thread so I don't know if the stack can respond to people with non-mthfr issues.
Not sure about the interactions between the stack and zinc/cefuroxim.
Thanks! I don’t think I have MTHFR. Never heard about it haha. I will google it to see what the symptoms are. Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
No blood test needed.
23andme testing cost 100$ USD then genetic genie for free.
http://geneticgenie.org/
-
Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
According to what I've read, with a dysfunctional MTHFR gene you have to take the right form of folate, which is methylfolate.
Some people determine if they have MTHFR problems through a genetic test like offered by 23andme. However, this only tests a selected number of SNPs (=locations of the gene), so in theory your copies of the gene could be defective even if the test says they are not. On the other hand, if the test says you have defective MTHFR genes, then you can be sure that you have a problem there.
“Methylfolate is a remarkable nutrient yet it can create significant side effects. Those who have MTHFR mutations (especially the C677T MTHFR mutation) learn that methylfolate is critical to take.”
http://mthfr.net/methylfolate-side-effects/2012/03/01/
-
Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it?€™s in Nanna?€™s stack. A bloodtest for MTHFR costs more than 600 euro.
According to what I've read, with a dysfunctional MTHFR gene you have to take the right form of folate, which is methylfolate.
Some people determine if they have MTHFR problems through a genetic test like offered by 23andme. However, this only tests a selected number of SNPs (=locations of the gene), so in theory your copies of the gene could be defective even if the test says they are not. On the other hand, if the test says you have defective MTHFR genes, then you can be sure that you have a problem there.
?€œMethylfolate is a remarkable nutrient yet it can create significant side effects. Those who have MTHFR mutations (especially the C677T MTHFR mutation) learn that methylfolate is critical to take.?€
http://mthfr.net/methylfolate-side-effects/2012/03/01/
It mentions 3 types of response of taking methylfolate and so far I could be either in category first or second response. I will update sooner or later regarding the progress. So be on the look out :)
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
Ok, wish you the best of luck.
Btw, do you happen to know if you have MTHFR? I have not read the whole thread so I don't know if the stack can respond to people with non-mthfr issues.
Not sure about the interactions between the stack and zinc/cefuroxim.
Thanks! I don’t think I have MTHFR. Never heard about it haha. I will google it to see what the symptoms are. Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it’s in Nanna’s stack. A bloodtest for MTHFR costs more than 600 euro.
No blood test needed.
23andme testing cost 100$ USD then genetic genie for free.
http://geneticgenie.org/
I don’t know if I can trust them. Check this topic about 23andme:
https://poiscenter.com/forums/index.php?topic=1234.msg11453#msg11453
-
I just bought the medicines from the prepack. And Excerdrin instead of those 3 medines. I hope to start wednesday with the stack. And I will take it at least 10 days before I test it.
My question is: can I keep taking other supplements like Zinc. I take Zinc for my prostate problems. Not sure if it helps. And also cefuroxim.
Ok, wish you the best of luck.
Btw, do you happen to know if you have MTHFR? I have not read the whole thread so I don't know if the stack can respond to people with non-mthfr issues.
Not sure about the interactions between the stack and zinc/cefuroxim.
Thanks! I don?€™t think I have MTHFR. Never heard about it haha. I will google it to see what the symptoms are. Does Nanna have MTHFR? Vitamin B9/11 is bad for MTHFR but it?€™s in Nanna?€™s stack. A bloodtest for MTHFR costs more than 600 euro.
No blood test needed.
23andme testing cost 100$ USD then genetic genie for free.
http://geneticgenie.org/
I don?€™t know if I can trust them. Check this topic about 23andme:
https://poiscenter.com/forums/index.php?topic=1234.msg11453#msg11453
I see and understand 23andme is not without its controversials but whether the service is legit or not it ultimately lead me to this POIS forum and stumble up nana1 thread which in turn helped me tremendously. You don't have to take the test since if you already purchased the supplements and try that if that works. I'm just letting you know how I discover the information that I have a genetic mutation. To be quite frank, at the time I used the 23andme service I was curious if it would help me cause I'm sure you understand that as a POIS sufferer I was desperate to find answers and would try anything. 100$ is a drop in the bucket compared to all the specialist doctors I went to which netted absolutely no results.
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Mel, I understand very good why you turned to 23andme. Because of your positive result with Nana’s stack I will start with it about two days. I had almost all the supplements for a few months. But I was lazy to start taking so many pills. Because I already take some pills. But now it’s sure that helped you and Nanna it’s worth to try it. I will let you the know the result about two weeks. I will ask my PoIS doctor about that MTHFR test.
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Mel, I understand very good why you turned to 23andme. Because of your positive result with Nana’s stack I will start with it about two days. I had almost all the supplements for a few months. But I was lazy to start taking so many pills. Because I already take some pills. But now it’s sure that helped you and Nanna it’s worth to try it. I will let you the know the result about two weeks. I will ask my PoIS doctor about that MTHFR test.
Good luck :)
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Just want to report back that I came across my first side effect with the supplement. I would wake up after several hours after going to sleep. Read that B12 can cause insomnia which haven't happen to me yet but instead interruptions. But after some googling, it mentions that intake of potassium might help.
https://forums.phoenixrising.me/index.php?threads/methyl-folate-insomnia.50342/
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I started yesterday with Nanna’s stack. Today I woke up with lower back pain. I already have UTI/prostitis. But after going trough this topic I read that Alpha GPC causes lower back pain. So I will start with 1 pill a day for a week. And then go to 2.
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So I've started using this stack once again, this time making sure I was following a vegan diet. Cutting out animal proteins has indeed helped immensely with my cognitive performance outside of POIS. I've been wondering, however: Is there any indication outside of climaxing that the stack is working for me?
I haven't gotten any additional cognitive benefit since I started the stack, but knowing the answer might give me a great deal of confidence. I'd test this out myself, but I've been very busy at work. Thanks in advance, Nanna.
-
The lowest vitamin B6 I could find is 50mg. So I bought pyridoxal-5-phosphate pills with 20mg of vitamin B6.
-
We're looking forward to your results, Vandemolen!
-
Hi All,
I know I'm behind on the conversation, but I just wanted to contribute anything I can. If you are trying the POIS Cascade stack, I would give it about 1 month to assess if it is working for you.
Note: Many of these supplements have slow diffusion across the blood/brain barrier and/or slow incorporation into the phospholipid bilayer. So it may take 3 to 4 weeks of consistent supplementation before you are able to assess the full benefit. I continue daily maintenance of supplementation with the POIS Cascade Stack even after seeing my symptoms disappear.
Both D3 and EPA are fat soluble, so it may take a month of consistent supplementation to see their full effects. B6 is water soluble and should kick-in within a couple of days. Many of the supplements in the POIS Cascade Stack have slow diffusion across the blood/brain barrier and/or slow incorporation into the phospholipid bilayer. So it could take 3 to 4 weeks of consistent supplementation before the effects can be assessed.
I've been wondering, however: Is there any indication outside of climaxing that the stack is working for me?
One of the ways I could tell when the POIS Cascade stack is working for me (apart from having an orgasm) is that my exercise induced sickness goes away. I used to get flu-like symptoms (sneezing) with CFS, IBS, diarrhea from heavy exercise that would last for 5 to 7 days.
Exercise: Exercise caused sneezing and runny nose in my left nostril. I also had exercise induced IBS with diarrhea, unusually long DOMS/recovery and chronic fatigue (5-8 days). I still can get fasciculation shortly after resistance exercise.
Now I do not get sick from exercise anymore! Also, the DOMS (https://en.wikipedia.org/wiki/Delayed_onset_muscle_soreness) from exercise have almost completely gone away and I recover faster.
Just want to report back that I came across my first side effect with the supplement. I would wake up after several hours after going to sleep.
Methyl-donors can shorten your sleep cycle. To prevent problems with sleep, I would avoid taking SAMe before bedtime. SAMe does not cause sleep problems for everyone, but sleep disturbance is a known side-effect of SAMe for some due to increased neurotransmitter production.
Do not take SAM-e within 5 hours of your typical bedtime or you may experience trouble going to sleep.
It may be wise to also avoid choline/lecithin right before bed. TMG (betaine) is fine to take before bed.
I would agree that those who are undermethylated can benefit from methyl-donors, but I do not think that I personally have a problem with methylation. My methylation levels are normal even when I am not taking the stack. So for me, this stack does not correct any methylation problems, but it maybe possible that those who are undermethylated can receive additional benefits from methyl-donors and certain B vitamins.
12. Methylation/homocysteine blood test:
I stopped taking the majority of my supplement stack (choline/B-vitamins/omega-3/CLA) more than a week prior to getting the blood test. No creatine loading. No creatine more than 3 days prior to the blood test. Avoided other supplemental sources of B-vitamins like sport drinks. The only supplement I took the day of the test was vitamin D3. My homocysteine levels are normal (test (https://i.imgur.com/vBiVjGw.png)).
In terms of the Betaherpesvirinae stack, I am sorry if I confused anybody about Indomethacin. Ibuprofen is not the same drug as Indomethacin. Indomethacin is about 50 times more potent (effective) COX-2 inhibitor than Ibuprofen, and it is about 430 times more effective COX-1 inhibitor than Ibuprofen. Indomethacin is a prescription-only drug.
An explaination of what the potency measure IC50 means can be found here (http://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561). Smaller IC50 values result in a stronger effect (stronger COX inhibition). For example, indomethacin is a stronger COX-1 and COX-2 inhibitor than aspirin.
(https://i.imgur.com/T0oUg8G.png)
----------------
(https://i.imgur.com/PEmdWFT.png)
Ibuprofen is not an anti-inflammatory drug because it has extremely low potency. According to the above chart, Ibuprofen is the least effective COX inhibitor there is, because it does not inhibit COX-1 or COX-2 efficiently. I explain this in more details here (http://poiscenter.com/forums/index.php?topic=2597.msg22750;topicseen#msg22750).
One more thing to consider is the pharmacokinetics. Taking indomethacin 30 minutes before orgasm will likely not be as effective since it requires more than an 2 hours to reach peak blood levels (post (http://poiscenter.com/forums/index.php?topic=2683.msg24664;topicseen#msg24664)).
Please forgive me if there were any question directed toward me that I missed. :)
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Now I do not get sick from exercise anymore! Also, the DOMS (https://en.wikipedia.org/wiki/Delayed_onset_muscle_soreness) from exercise have almost completely gone away and I recover faster.
I just wanted to add that I also no longer experience irritable bowel syndrome (IBS). I'm not sure exactly why it went away. I used to experience it all of the time (even without orgasm and POIS). I started experiencing relief from my stack-diet last year, but it wasn't until this year that I noticed my IBS slowly started to disappear. Even if I break my diet for a week or two, I still do not experience IBS. So this is still a mystery.
But I can say that, I have experienced more improvements over this past year than I have over the previous decade. I do think that the lifestyle changes I made last year through my diet and supplements (and occasional fasting) has improved my overall health and reduced inflammation in general.
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Since I take Nanna’s stack I have to urinate almost 10 times a day. Al that water with those pills...
I also had IBS because of POIS. The last years I don’t have IBS. Maybe because I use a lot of antibiotics for my UTI/prostatatitis.
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hi nanna1, first of all, I want to thank your contributions to the forum. I believe that your profession (if I remember correctly, biomedical engineer) and your dedication are of great help. I am in a very difficult situation since the end of February. Despite that, I decided to try your set of supplements and vitamins. but unfortunately, on the second day I had to leave them. I started to feel worse. people close to me just told me that I may also suffer from pudendal nerve neuralgia. I have been tested for the pudendal nerve. and the result is that apparently it is completely normal. yes it is true that the symptoms that I suffer especially since I rode a sleigh at the end of February last suggests that it could be a pudendal nerve neuralgia. but there are certain symptoms that I can not explain with the pudendal nerve neuralgia. since I have clearly worsened since the last release. and other symptoms are more associable to POIS. In fact they are the same as I had before that time I rode in a sleigh. Do you think POIS could have a neurological component?
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. My troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim.
Yes, you are right. I remember I read It. But I am on a very delicate situation. I can get out of this difficult situation. and I find myself in a more stable situation I could try again 3 or 4 weeks. but now I can not risk getting worse. I need to be more stable first.... Thanks Vandemolen.
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Yes. For some, its a very big component. I think as nanna1 postulates that POIS is an inflammatory response, so if your nerves are in the slightest compromised state (though still normal) however after POIS, with that increased inflammation, they will now will get significantly (clinically) pinched, disrupting nerve transmission and causing the symptoms - pain / paresis etc.
Do you think POIS could have a neurological component?
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Alrighty, so I just tried climaxing after about a week and a half of taking Nanna's POIS Cascade Stack, while following a strict vegan diet, while also having taken 250mg flushing Niacin two hours ago. Let's see how this goes.
Bear in mind, I'm also taking a low dose of Adderall due to my recently-diagnosed ADHD. However, I'm confident that these writings reflect the "default" state of my mind.
Five minutes after: Nothing too-too interesting. I have a strange, almost tension-like feeling in the front of my cranium (forehead to just before the parietal lobe), but I can still talk and type rather eloquently.
Ten minutes: Ugh. Tension headache is getting worse. Still, my symptoms usually don't start till about half an hour later.
Fifteen minutes: Yeah, I get the feeling I'm in the midst of a pretty typical POIS episode now. Constant headache, mild cognitive impairment, mostly whilst trying to talk to people. Hopefully the niacin helps.
Thirty to fifty minutes: Ughh, this blows. Now my eyes are starting to defocus, my headache stretches all around my head above the ears. Cognitive impairment comes and goes, with stretches of mild symptoms interspersed with short bursts of extreme difficulty.
Overall I'm currently having a very typical POIS episode. On the bright side, climaxes seem to take away my neuropathic pain, to the point where orgasms could substitute medication if it weren't for these cognitive issues. I will keep supplementing regardless.
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Did enyone get beter from this stuck?
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. My troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
When I googled folate I got vitamine b11 (b9 in the US), acid folic. That’s what I use. I saw that there is a difference between acid folic and folate. Maybe that’s a reason why it didn’t work?
So I just bought Vitals Folate 5-MTHF 800mcg. I see you have to take only 200mcg. So I will open the pill and divide it.
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Alrighty, so I just tried climaxing after about a week and a half of taking Nanna's POIS Cascade Stack, while following a strict vegan diet, while also having taken 250mg flushing Niacin two hours ago. Let's see how this goes.
Bear in mind, I'm also taking a low dose of Adderall due to my recently-diagnosed ADHD. However, I'm confident that these writings reflect the "default" state of my mind.
Five minutes after: Nothing too-too interesting. I have a strange, almost tension-like feeling in the front of my cranium (forehead to just before the parietal lobe), but I can still talk and type rather eloquently.
Ten minutes: Ugh. Tension headache is getting worse. Still, my symptoms usually don't start till about half an hour later.
Fifteen minutes: Yeah, I get the feeling I'm in the midst of a pretty typical POIS episode now. Constant headache, mild cognitive impairment, mostly whilst trying to talk to people. Hopefully the niacin helps.
Thirty to fifty minutes: Ughh, this blows. Now my eyes are starting to defocus, my headache stretches all around my head above the ears. Cognitive impairment comes and goes, with stretches of mild symptoms interspersed with short bursts of extreme difficulty.
Overall I'm currently having a very typical POIS episode. On the bright side, climaxes seem to take away my neuropathic pain, to the point where orgasms could substitute medication if it weren't for these cognitive issues. I will keep supplementing regardless.
Too bad it didn’t work. You have to use the stack for af least 1 month and then you are sure it worked or not. Some vitamins from the stack I have 60. So that’s for 30 days. Other things like vit b12 and fish oil are good for the health. So even when after 30 days the stack doesn’t work for me I will use those vitamins.
I also use other medicins. Like cefuroxim, fexofenadine and amitriptyline. Also magnesium and Zinc.
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@ Nanna is there an alternative for folate? I am allergic to cefuroxim, so I am going to use another antibiotic. Maybe co-trimoxazole for my UTI. But you can’t use folate.
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Yes. For some, its a very big component. I think as nanna1 postulates that POIS is an inflammatory response, so if your nerves are in the slightest compromised state (though still normal) however after POIS, with that increased inflammation, they will now will get significantly (clinically) pinched, disrupting nerve transmission and causing the symptoms - pain / paresis etc.
Do you think POIS could have a neurological component?
Ok, swell. Thank you for your answer.
In fact, I think there are several people in this forum who suffer from chronic pelvic pain. I have seen that there is also a disease classified as rare called pudendal neuralgia ... the pudendal nerve is apparently responsible for the perceptions of the pelvic, genital area, etc ...
This is why I was asking about posible relationship with neurological problems.... Maybe there is any relationship with pudendal neuralgia and POIS when having chronic pelvic pain....
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. Myr troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
I just stopped with Nanna’s stack. I got new antibiotics. I can’t take folate. My
POIS doctor was interested in the stack. He took a picture. So maybe when I will change antibiotics
I will give it another try.
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I think vegan diet is good for me.My brain fog disappear , and mood became better.
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. Myr troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
I just stopped with Nanna’s stack. I got new antibiotics. I can’t take folate. My
POIS doctor was interested in the stack. He took a picture. So maybe when I will change antibiotics
I will give it another try.
Sorry, Van, to use your post, forum IM is now working.
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Have you tried to isolate the treatment (for example, just following only the vegan diet)?
I think we have seen here various mixing and conflicting reports about the influence of a vegan/vegetarian diet, so I wouldn't get a definite conclussion. I think it could help because -in principle- you are removing sugary foods from your diets (especially if you don't consume food with additives). But if you eat carbs, that could prove counterproductive as well.
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Yeah, i agree here with you Observer, it is something metabolic related to
glucose, or lower sugar-carbs = no inflamation.
Me personaly tested vegan diet-done nothing for pois and owerall helth.
But in thouse wegan diet it was a lot of carbs -grains etc.
Then i tested hi protein and fat low carbs paleo diet, because
etleast 10 people repordet that they get rid of theirs pois complitly.
On this diet, after 20 days, my body started losing weight , and i feel
wery bad on it(enormes calory intake but losing weight deadly).
My personal answer on this is that i hawe low acid and my digestive
enzayms for fat not working ok, and if no acid then cant breake down
proteins.
So it didnt helped my pois, and i recovering from loseing weight,
by eating chokolate kinder smorfs.
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Hi,
Just want to report back on my status.
So far everything is normal and still able to O.
The current supplements I take are,
1. B12 Lozenge with L-5 MTHF.
2. Electrolyte powder containing magnesium and potassium.
3. Soylent, which has all the vitamins at 20% daily value.
I'm pretty much done here but if you have any questions, you can shoot me a PM.
Great job nana1,
See ya.
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2. Electrolyte powder containing magnesium and potassium.
I'm interrested by this point. It's like if I have an electrolyte deficiency after ejaculation. Can you give the name of this powder ?
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2. Electrolyte powder containing magnesium and potassium.
I'm interrested by this point. It's like if I have an electrolyte deficiency after ejaculation. Can you give the name of this powder ?
Sure b_jim
https://www.amazon.com/Emergen-C-Electrolyte-Replacement-Potassium-Magnesium/dp/B002HWRY5S?keywords=EMERGEN-C%2BELECTRO%2BMIX&qid=1540684122&sr=8-5&ref=sr_1_5&th=1
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Oh thanks !
I find it's a very nice point of view, few discussed in our forum.
I suspect a lack of electrolytes for several reasons :
- After ejaculation, I become very sensible to carbs especiialy sugar with diahreas. And I don't have the explanation : it could be a lack of electrolytes used for carbohydrates absorbtion.
- Semen is rich in electrolytes : lot of potassium and some magnesium.
- Ou of Pois, in summer when I work hard, I can"t sleep and I feel depressed for 1 day. I lost water and probably electrolytes.
- Chlorid element seems to play a role in my fasciculation symptom in/out of Pois so I put salt in my water or meals...
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Ingredients : vitamines C, E and group B
Zinc, manganese
Electrolytes : Mg, Ca, K, Ph, Na
Probiotics, melatonin, caffeine MSM (?)
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Hi Itsmel.
You sayed before about face after O:
On the physical aspect after an O,
1. My face looks like I aged several years.
2. My face would feel saggy or loose but after taking Excerdrin, my face feels nice and firm but I don't know which ingredients from Excerdrin caused this.
I hawe the same isues on face , look older several years an slugish face...
Excerdin hawe -cofein, paracetamol, aspirin(this is combination for migrains).
After O in pois i hawe migrains to, so my body is in migrains mode and flu like mode
too.
About your stuck for pois -
1. B12 Lozenge with L-5 MTHF.
2. Electrolyte powder containing magnesium and potassium.
3. Soylent, which has all the vitamins at 20% daily value.
What are you think is main solution from those 3 for your pois?
B12 Lozenge with L-5 MTHF because mutation?
All 3 togedher in sinergy slowe mutation isue?
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Oh thanks !
I find it's a very nice point of view, few discussed in our forum.
I suspect a lack of electrolytes for several reasons :
- After ejaculation, I become very sensible to carbs especiialy sugar with diahreas. And I don't have the explanation : it could be a lack of electrolytes used for carbohydrates absorbtion.
- Semen is rich in electrolytes : lot of potassium and some magnesium.
- Ou of Pois, in summer when I work hard, I can"t sleep and I feel depressed for 1 day. I lost water and probably electrolytes.
- Chlorid element seems to play a role in my fasciculation symptom in/out of Pois so I put salt in my water or meals...
No problem, b_jim, doesn't hurt to try. Good luck!
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Hi Itsmel.
You sayed before about face after O:
On the physical aspect after an O,
1. My face looks like I aged several years.
2. My face would feel saggy or loose but after taking Excerdrin, my face feels nice and firm but I don't know which ingredients from Excerdrin caused this.
I hawe the same isues on face , look older several years an slugish face...
Excerdin hawe -cofein, paracetamol, aspirin(this is combination for migrains).
After O in pois i hawe migrains to, so my body is in migrains mode and flu like mode
too.
About your stuck for pois -
1. B12 Lozenge with L-5 MTHF.
2. Electrolyte powder containing magnesium and potassium.
3. Soylent, which has all the vitamins at 20% daily value.
What are you think is main solution from those 3 for your pois?
B12 Lozenge with L-5 MTHF because mutation?
All 3 togedher in sinergy slowe mutation isue?
Hi Hopeoneday, the main ingredient for me here is B12 Lozenge with L-5 MTHF.
When I look up paracetamol, apparently it increases aldosterone and decreases cortisol.
https://www.ncbi.nlm.nih.gov/pubmed/27217499
But I don't have enough knowledge to interpret them but it could be a lead.
Maybe I have low aldosterone or high cortiosol?
Good luck!
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I've been taking nanna1's stack for about two months now. I've made some small modifications over the past few weeks, and have been completely symptom-free for the past week.
It's hard to tell whether this trend will continue, but I've certainly never experienced such a strong placebo effect throughout the past couple years of debugging POIS.
I posted more details about this here: https://poiscenter.com/forums/index.php?topic=2831.0 (https://poiscenter.com/forums/index.php?topic=2831.0)
Nanna1 - thank you so much for what you do! I feel like I'm finally seeing the light at the end of the tunnel.
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I'm a new POISer in this forum and I'm on Nanna1's POIS stack since two weeks ago but I have not noticed any much improvement yet (maybe it takes much longer time?). I had the first NE tonight since I started, but unfortunatly it happened at the same day as a got a cold break out (actuallt the cold caused the NE due to bad sleep) so I'm not sure what causes the headache now.. ;/.. But I feel that familiar tense feeling in the forehead that use to come with POIS. I had POIS since I was teenage. Over 40 now and its a life challange... Tryed to do the survey today but was stopped by the headache. I believe I have much experience to contribute.
I wonder why there is a strikeout on the folloing ingredients on Nanna1's original post. Have they been removed from the stack?
---Benfotiamine, vitamin B1 (150mg) [h1H downregulator]
---eicosapentaenoic acid, EPA (900mg) [AA synthesis inhibitor, AA blocker]
---docosahexaenoic acid, DHA (150mg) [AA synthesis inhibitor]
Should the stack also be taken right after a NE? What is the best thing to do after a NE anyway?
I have also aired an idea about blood vessel elasticity as a contributing factor to POIS and I would be happy to hear Nanna1's and all of your others thoughts about that. Here is the thread: https://poiscenter.com/forums/index.php?topic=2832.0
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. My troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
I will give it another try. Because when I tried the first time I had candida. I still have candida, almost 2 months now. I hope to get rid of candida in a week because my doctor gave me an anti fungus medicine. Maybe it will work when I don’t have candida.
I will also try taurine when out of Candida.
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Methyl folate 400ug seems to give me brain fog for a few hours every time i try this stack. I have very low folate so why is this the case, is it due to overmethylation? I don't seem to have the characteristics of over methylation so its strange to me. I've heard normal folic acid is bad so what do I do now?
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Ps I tried looking for 200ug metafolin and couldn't find anywhere
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Just an update,
The effects of the B12+B9 are beginning to subside but the effects are still overall positive so it still my supplement to go but I take it once a week because if I take it on the daily basis my cortisol shot up near the higher range. That's when I stopped and then took it once it week before my cortisol normalize. This supplement has this bell curve effect to it as one of the member linked and to my experience it is definitely true.
I would like to join the discussion about the Cox-2 inhibitor. As I stated initially from the start I took Tylenol for premature ejaculation and it works really well but it also greatly alieves some of the nuero issues such as anxiety, depression and increase verbal fluency. I felt that I was a whole new person. I started to look into why only Tylenol would help but not Ibuprofen and Asprin and based on the chart that nana1 posted, Tylenol has higher rating for COX-2 inhibitor than the others and can confirm that because I tried Ibuprofen and Asprin and they dont give me the same results as Tylenol.
For people who have PE, I urge you to try Tylenol or Acetaminophen and they are OTC.
Currently I'm trying to get my hands on the generic version of Celebrex.
Although I'm curious about the statement made by nana1 regarding the vitamin D that its even much stronger than Tylenol or paracetamol which means it should help my conditions but the last time I tried it, I felt it gave me more inflammation but I found that you must supplement with other vitamins such as K2 and Magnesium so I'll report back on that.
brb
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Just an update,
The effects of the B12+B9 are beginning to subside but the effects are still overall positive so it still my supplement to go but I take it once a week because if I take it on the daily basis my cortisol shot up near the higher range. That's when I stopped and then took it once it week before my cortisol normalize. This supplement has this bell curve effect to it as one of the member linked and to my experience it is definitely true.
I would like to join the discussion about the Cox-2 inhibitor. As I stated initially from the start I took Tylenol for premature ejaculation and it works really well but it also greatly alieves some of the nuero issues such as anxiety, depression and increase verbal fluency. I felt that I was a whole new person. I started to look into why only Tylenol would help but not Ibuprofen and Asprin and based on the chart that nana1 posted, Tylenol has higher rating for COX-2 inhibitor than the others and can confirm that because I tried Ibuprofen and Asprin and they dont give me the same results as Tylenol.
For people who have PE, I urge you to try Tylenol or Acetaminophen and they are OTC.
Currently I'm trying to get my hands on the generic version of Celebrex.
Although I'm curious about the statement made by nana1 regarding the vitamin D that its even much stronger than Tylenol or paracetamol which means it should help my conditions but the last time I tried it, I felt it gave me more inflammation but I found that you must supplement with other vitamins such as K2 and Magnesium so I'll report back on that.
brb
I've tried Celebrex I think for five days and I didn't notice any change. I haven't tried Paracetamol extensively because I usually look down upon it. Was paracetamol instant for you? Or did it take more time to be effective?
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
Before going on a holiday to Dubai I googled a bit and came out at this article that says that 90% of the Dubai population has a vitamin D defiency. I know that in Dubai they spend a lot of time inside in malls and airconditioned areas. My point is that it depends on your lifestyle. If you live in The Netherlands like me and you go outside a lot your vitamin D will be ok. And if you live in Dubai and you spend the most of your time indoors then your vitamin D will not be ok.
I had a vitamin D level of 16 and I go a few times in a year on holidays to the sun. Only 50.000IE a week helped to raise my level. Now it is 160.
https://gulfnews.com/going-out/society/90-of-uae-population-vitamin-d-deficient-says-dha-official-1.2113556
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
Before going on a holiday to Dubai I googled a bit and came out at this article that says that 90% of the Dubai population has a vitamin D defiency. I know that in Dubai they spend a lot of time inside in malls and airconditioned areas. My point is that it depends on your lifestyle. If you live in The Netherlands like me and you go outside a lot your vitamin D will be ok. And if you live in Dubai and you spend the most of your time indoors then your vitamin D will not be ok.
I had a vitamin D level of 16 and I go a few times in a year on holidays to the sun. Only 50.000IE a week helped to raise my level. Now it is 160.
https://gulfnews.com/going-out/society/90-of-uae-population-vitamin-d-deficient-says-dha-official-1.2113556
Perhaps but I used to go alot outside before POIS. In fact I developed my tan skin color because of the amount I spent outside. I was very extroverted before POIS.
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...going on a holiday to Dubai...
Have a nice, POIS-free visit!
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...going on a holiday to Dubai...
Have a nice, POIS-free visit!
Thanks. I have been there a few months ago. It was POIS-free holiday because I abstained. But I was not feeling wel a few days. Back then I did not know why, but now I know it was candida.
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
Before going on a holiday to Dubai I googled a bit and came out at this article that says that 90% of the Dubai population has a vitamin D defiency. I know that in Dubai they spend a lot of time inside in malls and airconditioned areas. My point is that it depends on your lifestyle. If you live in The Netherlands like me and you go outside a lot your vitamin D will be ok. And if you live in Dubai and you spend the most of your time indoors then your vitamin D will not be ok.
I had a vitamin D level of 16 and I go a few times in a year on holidays to the sun. Only 50.000IE a week helped to raise my level. Now it is 160.
https://gulfnews.com/going-out/society/90-of-uae-population-vitamin-d-deficient-says-dha-official-1.2113556
Perhaps but I used to go alot outside before POIS. In fact I developed my tan skin color because of the amount I spent outside. I was very extroverted before POIS.
Well then maybe your vitamin D level is ok. But if you are planning to do a bloodtest for something else it would be an idea to check your vitamin D too. Some people do get a lot of sun, but their body can not manage it. I can not remember the medicial term.
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
It would be a good ideal with a vitamin d test, at least it can tell you what is your base line and plan from there. I read that the only time you can make vitamin d depends where you live and the sun position between 10-3. During the summer time the only time I would get sun light is walking to the subway station to work so basically it would be rare for me to get enough sunlight to probably make any difference.
Btw, did you get any side effects from taking celebrex?
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
Before going on a holiday to Dubai I googled a bit and came out at this article that says that 90% of the Dubai population has a vitamin D defiency. I know that in Dubai they spend a lot of time inside in malls and airconditioned areas. My point is that it depends on your lifestyle. If you live in The Netherlands like me and you go outside a lot your vitamin D will be ok. And if you live in Dubai and you spend the most of your time indoors then your vitamin D will not be ok.
I had a vitamin D level of 16 and I go a few times in a year on holidays to the sun. Only 50.000IE a week helped to raise my level. Now it is 160.
https://gulfnews.com/going-out/society/90-of-uae-population-vitamin-d-deficient-says-dha-official-1.2113556
Yes and also depends on the sun position and your location. Generally we want to have the sun at the highest altitude to receive optimal vitamin d which I think it was 10-3 but that's like when everyone is working indoors like me.
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Hey Nas,
Paracetamol works within 2 hours but the current issue for me is that it has become less effective over time. I suspect that I have high levels of prostaglandin due to vitamin d deficiency but I can't tolerate vitamin d and it could be that I also have VDR (vitamin d receptor) issue from the genetic testing. Not sure if there any relations and dont have knowledge on them so I can't comment. They are,
VDR TAQ +/-
VDR BMS +/-
Sorry it didn't work out for you. Have you also try vitamin d?
Hey Itsme
Yeah I did but I also tried it with other stuff so I'm not sure if it works at all. Vitamin D is a mast cell stablizer so I might visit it again, plus it can be found anywhere so its less of a pain to buy.
In fact, I might do a test to see if I'm deficient. I very much doubt it since I live in the hottest spot on earth so there aren't really any lack of vitamin d in my environment.
It would be a good ideal with a vitamin d test, at least it can tell you what is your base line and plan from there. I read that the only time you can make vitamin d depends where you live and the sun position between 10-3. During the summer time the only time I would get sun light is walking to the subway station to work so basically it would be rare for me to get enough sunlight to probably make any difference.
Btw, did you get any side effects from taking celebrex?
No not really. I took it for five days and I didn't really feel anything changing.
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I saw some post here and other threads about COX inhibitors and Tylenol (a.k.a. acetaminophen or paracetamol) and wanted to try to advance the conversation a little. This post is only for POISers who are taking prepacks or pharmaceutical drugs Nothing that I say here can substitute for treatment by a personal physician.
Excedrin (https://www.excedrin.com/products/) (acetaminophen, aspirin, caffeine) is a drug combination that is FDA approved (in the USA) to treat migraines and is an over-the-counter (OTC) drug. These three drugs taken together are synergetic and more effective together than if they are taken individually. Some POISers try the drugs one-at-a-time (like trying only acetaminophen) to see if it works before stacking the other drugs. Trying the drugs one-at-a-time will not be effective at stopping POIS. From my experience and from what other POISers have said, trying the drugs individually will result in you taking more doses over longer periods of time. More doses lead to more side-effects. Taking the 3-drug combination (Excedrin) can help prevent POIS with one dose (this means less drugs and fewer side-effects).
Excedrin:
- caffeine: PDE(1,4,5) inhibitor, adenylyl cyclase inhibitor, NF-kB downregulator, vasocontrictor (through adenosine receptor)
- aspirin: antioxidant, COX inhibitor, vasoconstrictor (through PGE2 downregulation)
- acetaminophen: cannabinoid reuptake inhibitor, NF-kB downregulator
My first trial of Excedrin is discussed here (https://poiscenter.com/forums/index.php?topic=2502.msg24507#msg24507). In my tests of Excedrin, I found that the drug is most effective when timed before the orgasm. I made the concept figure below to explain why I believe timing is very important:
(https://i.imgur.com/vyxg6r7.png)
Acetaminophen, aspirin, caffeine have similar timing pharmacokinetics. After you start (tstart) the Excedrin dose, the blood concentration peaks (tmax) at about 90 min. Then there is roughly a 2 hour window (t1/2) when it is safe to orgasm. The reason for waiting until after tmax is that absorption of the drug from the blood stream into the cells usually lags behind in time by about 30min. Below are more accurate plasma time-points graphs for Tylenol (Acetaminophen). Note that it takes longer for Acetaminophen to cross the blood-brain-barrier (BBB)(see Mean Cerebrospinal Fluid Values| right graph):
(https://i.imgur.com/qnFs5kw.png)
Figure from: The Role of Intravenous Acetaminophen in Multimodal Pain Protocols for Perioperative Orthopedic Patients (P. LACHIEWICZ, 2013) (http://www.iqanda-cme.com/assets/pdf/LACHIEWICZ.pdf)
When you time the drug(s) properly, they are more effective at stopping the arachidonic acid cascade. And when the drug is more effective, you can take less of the drug and experience fewer side-effects. If you do not time the drugs properly, they will be less effective and you will have to take more of the drugs to experience relief (more-drugs = more-side-effects). So the timing is a safety issue just as much as it is a POIS-relief issue.
There are several differences between migraines and POIS. So I did a few (about nine) modified-Excedrin trials which resulted in the Beta-herpes virus stack (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). This stack is customized more for POIS rather than for migraines. In the Beta-herpes virus stack, I basically replaced aspirin with indomethacin and added vitamin D3. Selenium and N-acetylcysteine were added as detox antioxidants to boost glutathione (Ref (https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12808)). For me, this stack was 100% effective with a single dose, and it was more effective at preventing POIS than Excedrin.
Indomethacin (oral, 50mg) (tmax = 2 hours, t1/2 = 4 hours):
(https://i.imgur.com/udhXwgm.png)
Figure from: TIVORBEX (indomethacin): The first low-dose SoluMatrix indomethacin. (https://www.tivorbexhcp.com/indomethacin-clinical-trials/) (blood-plasma time points)
More indomethacin trials/experiences from other POISers can be found here (https://poiscenter.com/forums/index.php?topic=2502.msg24700#msg24700). In theory, the COX inhibitor Diclofenac is the best COX inhibitor for POIS. It is a better COX-2 inhibitor than indomethacin (see post (http://post)) and has better BBB penetration. However, I have never tried Diclofenac. So I do not know whether it works in practice.
Diclofenac (oral, 50mg) (tmax = 90min, t1/2 = 80 min):
(https://i.imgur.com/VPBAilB.jpg)
Figure from: DYLOJECT ACHIEVES CMAX 5 TO 7 TIMES ORAL IMMEDIATE-RELEASE (IR) DICLOFENAC (https://www.pfizerpro.com/product/dyloject/pain/pharmacokinetics)
Celebrex is not a good prepack drug since it has to be taken long-term. With that said, no COX-inhibitor can prevent POIS on its own. With that said, from my trials of the Excedrin and alternative COX-inhibitors, it seemed that I needed a COX-inhibitor and a NF-kB inhibitor to prevent POIS. Taking only COX inhibitors or taking only NF-kB inhibitors did not work no matter how high the dose was. But I must reiterate, for any drug you try, the only way to know if it works or not is to have the right timing and therapudic dose information.
Please consult your doctor to make sure that these drugs are safe for you. Also make sure that any other medications you may be taking do not interact negatively with COX inhibitors, cannabinoids or caffeine before trying the Beta-herpes Virus Stack.
Some additional plasma time-point graphs are shown below for other popular supplements:
N-Acetylcysteine (tmax = 2 hours, t1/2 = 18 hours):
(https://i.imgur.com/fN9FRax.jpg)
Figure from: Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study (SC Green, et. al., 2016) (https://www.sciencedirect.com/science/article/pii/S0011393X16300625)
Tri-methyl-glycine (betain, TMG) (tmax = 55 min, t1/2 = 14 hours):
(https://i.imgur.com/NbMA702.jpg)
Figure from: Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria (BC Schwahn, et. al., 2003) (http://)
Taurine (tmax = 2 hours, t1/2 = 1 hour):
(https://i.imgur.com/pJi4UAv.jpg)
Pharmacokinetics of Oral Taurine in Healthy Volunteers (M Ghandforoush-Sattari, et. al., 2010) (https://www.hindawi.com/journals/jaa/2010/346237/fig2/)
Vitamin C (ascorbate, oral 1.25g) (tmax = 2 hours, t1/2 = 7 hour):
Vitamin C pharmacokinetics:
(https://i.imgur.com/HNRAQKH.png)
Fig. from: "Vitamin C pharmacokinetics: implications for oral and intravenous use", Ann Intern Med. 2004 (Ref (https://www.ncbi.nlm.nih.gov/pubmed/15068981)) (click figure to show full resolution)
Nicotinic acid (flush niacin) (tmax = 4 hours, t1/2 = 2 hours):
(https://i.imgur.com/tRCO9Su.png)
Figure from: Niacin and fibrates in atherogenic dyslipidemia: Pharmacotherapy to reduce cardiovascular risk (MJ Chapman, 2010) (https://www.sciencedirect.com/science/article/pii/S0163725810000252)
*Update: I added the timing (90min) and dosage (50mg) information for Diclofenac to satisfy a concern that Muon had.
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In theory, the COX inhibitor Diclofenac is the best COX inhibitor for POIS.
Then I must disappoint you and the community. Waldinger has done a pilot study with Diclofenac. Patients took 25 mg Diclofenac 2 hours before sexual activity. He did not translate this into an official study due to insufficient results. A few patients did respond to it with reduction of POIS symptoms but many of them did not, he did not specify numbers though.
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Welcome back Nanna!
Thanks for the information, you mention using indomethacin but honestly indomethacin is not a good drug for your stomach. What do you think about piroxicam? Perhaps it is a safer Cox inhibitor.
Unfortunately, Excerdin is not available where I live, I can still buy it from Amazon though, we'll see.
Also I know you have your own Herpers-POIS theory. But how about POIS being a form of Mast Cell Activation Disorder? I have contacted two rare disease specialists and they both agree that there is a connection. I wish we can your two cents on this matter.
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Nothing that I say here can substitute for treatment by a personal physician.
Thanks for that, nanna1!
Splendid writeup & graphics!!
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In theory, the COX inhibitor Diclofenac is the best COX inhibitor for POIS.
Then I must disappoint you and the community. Waldinger has done a pilot study with Diclofenac. Patients took 25 mg Diclofenac 2 hours before sexual activity. He did not translate this into an official study due to insufficient results. A few patients did respond to it with reduction of POIS symptoms but many of them did not, he did not specify numbers though.
Muon, is it possible to post more here about that pilot study?
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Hi Muon,
In theory, the COX inhibitor Diclofenac is the best COX inhibitor for POIS.
Then I must disappoint you and the community. Waldinger has done a pilot study with Diclofenac. Patients took 25 mg Diclofenac 2 hours before sexual activity. He did not translate this into an official study due to insufficient results. A few patients did respond to it with reduction of POIS symptoms but many of them did not, he did not specify numbers though.
Thank you for your comments. It is not disappointing at all. This is exciting! I believe your concerns about Diclofenac were addressed in my previous post.
(about Excedrin)...These three drugs taken together are synergetic and more effective together than if they are taken individually.
More indomethacin trials/experiences from other POISers can be found here (https://poiscenter.com/forums/index.php?topic=2502.msg24700#msg24700)...With that said, no COX-inhibitor can prevent POIS on its own. With that said, from my trials of the Excedrin and alternative COX-inhibitors, it seemed that I needed a COX-inhibitor and a NF-kB inhibitor to prevent POIS. Taking only COX inhibitors or taking only NF-kB inhibitors did not work no matter how high the dose was. But I must reiterate, for any drug you try, the only way to know if it works or not is to have the right timing and therapudic dose information.
The therapudic dose for Diclofenac is 50mg. I added a plasma time point graph to clarify this.
Diclofenac (oral, 50mg) (tmax = 90min, t1/2 = 80 min):
(https://i.imgur.com/VPBAilB.jpg)
Figure from: DYLOJECT ACHIEVES CMAX 5 TO 7 TIMES ORAL IMMEDIATE-RELEASE (IR) DICLOFENAC (https://www.pfizerpro.com/product/dyloject/pain/pharmacokinetics)
According to published data (see post (https://poiscenter.com/forums/index.php?topic=2502.msg25518#msg25518)) Diclofenac is only comparable to Indomethacin at equal concentrations. This means (Diclofenac 50mg, acetaminophen 500mg, caffeine 130mg) vs. (Indomethacin 50mg, acetaminophen 500mg, caffeine 130mg) vs. (Aspirin 500mg, acetaminophen 500mg, caffeine 130mg).
I did a quick search and the only published trial of Diclofenac for POIS that I could find is the following:
"An alternate hypothesis proposed by Ashby and Goldmeier in their case report is that POIS is driven by a disordered cytokine or neuroendocrine response. This was supported by the improvement of POIS symptoms in the patient after administration of prophylactic diclofenac, a non-steroidal anti-inflammatory medication... Another successful trial of therapy with non-steroidal anti-inflammatory medication (diclofenac) succeeded in alleviating symptoms (up to 80% improvement) and allowed the patient in that case report to increase his sexual frequency from 2 to 4 times a month." -Post-Orgasmic Illness Syndrome: A Review (https://www.sciencedirect.com/science/article/pii/S2050052117301166#bib3)
----------------------------------------------------
Hi Nas,
Thanks for your questions and comments. I never experienced stomach problems when I took aspirin or indomethacin, but I only took them a few times (not chronically). Any strong COX-1 inhibitor that is taken daily over a long period of time will increase the risk of gastrointestinal (stomach) problems. This is why I included the detox antioxidants selenomethionine and N-acetylcysteine which boost glutathione production. The research indicates that selenomethionine detoxifies indomethacin and N-acetylcyteine detoxifies acetaminophen/Tylenol (Ref1 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614100/)). For example,
selenomethionine:
Selenomethionine is needed to produce all the glutathione recycling enzymes, glutathione peroxidase (https://en.wikipedia.org/wiki/Glutathione_peroxidase#Structure). Selenium can repair peroxidative damage and increase activity of the three main anti-oxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase above normal levels (Ref (https://www.ncbi.nlm.nih.gov/pubmed/21532324)).
(https://i.imgur.com/wscBGiA.png)
I do not have a way of independently verifying whether selenium and N-acetylcysteine are effective at preventing side-effects. So take the usual precautions and seek a physician's counsel. One of the main reasons I include N-acetylcysteine in the Beta-herpes virus Stack is because there is research and human clinical trials for using it as drug detox (Ref1 (https://poisoncontrol.utah.edu/newsletters/pdfs/toxicology-today-archive/Vol7_No1.pdf), Ref2 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf)). In terms of Piroxicam, I am not familiar with this NSAID, but I would be glad to hear of your experience. If it is a better way of reducing prostaglandin (like PGE2 and PGF2alpha) production, then I'm sure it will benefit the community.
Mast cells are definitely important. But I will post some thoughts about mast cells in a different thread, because I think my answer will be quite complex. Thanks again Nas!
----------------------------------------------------
Nothing that I say here can substitute for treatment by a personal physician.
Thanks for that, nanna1!
Splendid writeup & graphics!!
Thanks demografx!
----------------------------------------------------
To All,
I know I have not been quick with replies. There is a lot on my plate right now. I am a post-doctoral researcher in the biomedical field, and I am applying for a professor position at a university. This means I have to publish a lot of papers and satisfy collaborators which takes a lot of time. Please forgive me. I wish you all well!
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I see that in some patients from mcas using aspirin is one of the main
things for realefe.
But all this nsaids , aspirin etc for some peoples could hawe nasty side
effects....
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I am applying for a professor position at a university.
(https://www.wannaparty.in/media/catalog/product/cache/1/image/9df78eab33525d08d6e5fb8d27136e95/2/8/28721_hexl_colorblockinggoodluck.jpg)
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Ok thanks for the explanation nanna. I don't know how you are able to perform in university. I'm a physicist myself but homebound. Everytime I try working towards a normal lifestyle I'm crashing.
Muon, is it possible to post more here about that pilot study?
This is the only info I've got. I could send Waldinger an email and ask for more details, don't know whether he will respond.
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Thanks for checking up with poiscenter with periodic updates nana1, we really appreciated it.
Regarding the NSAIDS, Celebrex and Diclofenac are both NSAID but Celebrex is a COX-2 inhibitor opposed to Diclofenac which does both COX-1 and COX-2. With both similar side effects, wouldn't it be safer to use COX-2 since you don't want to necessary want to mess with COX-1? I recall romies who posted early in this topic and another user searched on this forum who had success with it but Nas did not, then it got me thinking when you said taken for long term. Does that mean it needs to be build up in your system? I tried to reach out to the two users but haven't got an reply.
Btw, about Diclofenac via wiki
"Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent ? a 95% decline by 2003[35]"
Wow! :o
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It was Egordon who used Celebrex, I wonder if they have any updates regarding the usage.
https://poiscenter.com/forums/index.php?topic=524.0
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I'm a physicist
(https://res.cloudinary.com/teepublic/image/private/s--6VWbAvb---/t_Preview/b_rgb:3b2134,c_limit,f_jpg,h_630,q_90,w_630/v1482470187/production/designs/983394_1.jpg)
Just posting as good-natured humor :) :) :)
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I think I will be pointing my muonic cannon towards Chile today 8).
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I think I will be pointing my muonic cannon towards Chile today 8).
This is the first time, I ever, even remotely, see a gist of humor coming from Muon :P
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Hi Itsmel,
Thanks for your questions and comments.
Regarding the NSAIDS, Celebrex and Diclofenac are both NSAID but Celebrex is a COX-2 inhibitor opposed to Diclofenac which does both COX-1 and COX-2. With both similar side effects, wouldn't it be safer to use COX-2 since you don't want to necessary want to mess with COX-1?
This is a good question. The short answer is that I don't yet know the answer to the (selctive-COX-2 vs. non-specific-COX ) inhibitor question. Only COX-2 is upregulated by inflammation (via NF-kB and JNK). However, the goal is to block PGE2 production. And since both COX-1 and COX-2 can produce PGE2 from arachidonic acid, it is not clear whether selective COX-2 inhibitors alone can prevent the rise in prostaglandins. I found this article which suggest that both COX-1 and COX-2 need to be inhibited:
"To better understand the role of COX induction and prostaglandin production in herpesvirus replication and pathogenesis, we analyzed the effects of specific and nonspecific COX inhibitors on PRV replication. The inhibition of either COX-1 or COX-2 by use of an isoform-specific inhibitor caused a moderate inhibition of PRV growth (25- to 30-fold). However, when both COX isoforms were inhibited simultaneously, either with a nonspecific COX inhibitor or with a combination of specific COX-1 and COX-2 inhibitors, PRV infectious yields were dramatically reduced (>200,000-fold). We performed ultrastructural studies to determine the effects of COX inhibitors on capsid and virion maturation. COX inhibition during PRV infection led to an accumulation of unusual empty capsid-like structures in the nuclei of infected cells. Our data establish a role for COX-1 and COX-2 in facilitating the efficient growth and replication of PRV in primary cells."
-Cyclooxygenase-1and -2 Are Required for Production of Infectious Pseudorabies Virus (https://jvi.asm.org/content/78/23/12964)
So my best guess is that inhibiting both COX-1 and COX-2 over a short time period (short half-life, t1/2) would be better.
when you said taken for long term. Does that mean it needs to be build up in your system?
Yes, celecoxib/Celebrex has to build up in your body for about a week before you can see the full effects. Here is the celecoxib dosage (see post (https://poiscenter.com/forums/index.php?topic=2683.msg23846#msg23846)). Here is the Celebrex fact sheet (Ref1 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020998s026lbl.pdf))
Btw, about Diclofenac via wiki
"Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent ? a 95% decline by 2003[35]"
Wow! :o
Good observation! It's hard for me to comment much on diclofenac since I don't have personal experience with it. It doesn't bother me that diclofenac is toxic to birds because other species have different drug-metabolism enzymes than we do. For example, tea, dark chocolate and coffee are all lethal to carnivores like dogs and cats, but can be quite healthy for omnivores like humans. With that said, the toxicity of diclofenac may still be a problem in humans when used long-term, so it is worth looking into its safety or finding alternative COX inhibitors. There may be safer and more effective COX inhibitors than diclofenac.
The ideal COX inhibitor for the Beta-herpes virus stack would have the following properties:
- (COX-1 IC50) >= (COX-2 IC50), inhibits COX-2 more than or equal to inhibiting COX-1
- High single-dose bioavailability (Cmax > IC50, for both COX-1 and COX-2)
- Short half-life (t1/2 < 2 hours)
IC50 is the Concentration needed to Inhibit 50% of the COX-(1,2) protein. Cmax is the maximum Concentration that absorbs into the blood steam or the bioavailability. More about IC50 is explained here (https://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561).
Properties 1 and 2 define the effectiveness of the drug. While properties 2 and 3 basically define the safety of the drug. For property 2, higher bioavailability means that less of the drug has to be taken. For property 3, a short half-life means that the drug is only active when it is needed (during-orgasm) but not active very long afterwards when it is not needed. Gallic acid (https://poiscenter.com/forums/index.php?topic=2597.msg23199;topicseen#msg23199) is a natural COX-2 inhibitor that has properties 2 and 3. Gallic acid is found in tea and has a good safety reputation in humans. It also seems to be good for birds (Ref (https://www.ncbi.nlm.nih.gov/pubmed/28521034))! If someone finds a COX-1 inhibitor that has properties 2 and 3, then it could be paired with gallic acid to effectively have all three properties....Or since aspirin is a COX-1 inhibitor, gallic acid (100mg) could be taken with the Excedrin, vitamin D3, selenomethione and N-acetylcysteine (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) stack (2 hours pre-activity). Thanks for your thoughtful questions :)
I think I will be pointing my muonic cannon towards Chile today 8).
LOL! Awesome ;D
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Has anyone on this forum been tested for PGE2?
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Hey nanna1, thanks for your efforts!
I have a question about the SAM-e dosage: is it total 200mg a day, or 400mg (2x 200mg). From the way the list is constructed I can assume it is 200mg (2x 100mg), however this seems like a very small dosage (given SAM-e has low oral bio availability) also it's not possible to find 100mg tablets anywhere (and breaking them is not an option).
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I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.
I will report when I tried it again. Now my fingers, feet and skull are very dry. My troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.
Nanna, could my shortage of IgM be the reason why your stack did not work for me? I am in a POIS state since I tried this stack.
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Hi taurusthree, each dose listed in the original post is per serving. So SAMe 2x(200mg) = 400mg per day. I hope that helps.
Hi Vandemolen,
Nanna, could my shortage of IgM be the reason why your stack did not work for me? I am in a POIS state since I tried this stack.
There seems to be a pattern emerging in the Medical Data/test thread (https://poiscenter.com/forums/index.php?topic=2684.msg23787#msg23787) show immunodeficiency in many of us POISers.
A few patterns in the data:
--4 of us have low neutrophil counts (nanna1 (http://poiscenter.com/forums/index.php?topic=2684.msg24052#msg24052), quotz (http://poiscenter.com/forums/index.php?topic=2684.msg24642#msg24642), BluesBrother (http://poiscenter.com/forums/index.php?topic=2684.msg24765#msg24765), certainlypois2 (http://poiscenter.com/forums/index.php?topic=2684.msg24532#msg24532)).
--3 of us show normal neutrophil levels (Muon, Muon's brother (http://poiscenter.com/forums/index.php?topic=2684.msg24021#msg24021), Nas).
--1 of us show low monocyte levels (quotz)
--1 of us show low Natural Killer cell (NK cells) levels (muon)
--1 of us show low lymphocyte levels (muon)
--1 of us show lymphocytes do not increase in response to lung infection (aswinpras06 (https://poiscenter.com/forums/index.php?topic=2684.msg24812#msg24812))
I am only showing data of people who self-report, but Hopeoneday has also found several cases of neutropenia in POISers posted elsewhere. Immunodeficiency diseases are rare (low prevalence, post (https://poiscenter.com/forums/index.php?topic=2695.msg24966#msg24966)), so this seems very interesting. Most of the data is on Complete Blood Counts (CBC, neutrophils), but I think Muon's low NK cell levels is the most interesting result so far. This is because NK cells are the primary virus killers of the immune system. These immune deficiencies are all associated with the innate immune system (https://en.wikipedia.org/wiki/Innate_immune_system). The innate immune cells (monocytes, neutrophils, NK cells) are the first responders to a harmful event (infection, cancer, poison, etc...). If the innate immune system fails, then the adaptive immune system (https://en.wikipedia.org/wiki/Adaptive_immune_system) (T cells, B cells, etc...) takes over and tries to control the harmful event.
I mention all this because low immunoglobulin levels are sometimes used to measure immunodeficiency diseases. But this is usually done using the IgG subclasses (IgG1, IgG2, IgG3, IgG4). Kurtosis and Muon have written a few good post on immunoglobulins. I don't see any patterns in the POISer data related to IgM, and I do not see how this result would affect the stack. Immunoglobulin are mostly related to the innate and adaptive immune systems. But both stacks that I propose (vegan diet/POIS Cascade stack and Betaherpesvirinae stack) are manipulating the intrinsic immune system (https://en.wikipedia.org/wiki/Intrinsic_immunity) (arachidonic acid cascade, NF-kB, etc...). The Betaherpesvirinae stack directly suppresses the intrinsic immune system, but the POIS Cascade stack is suppose to reduce inflammation without suppressing any immune function. There could be a connection between IgM levels and the stacks, but I do not see any direct connection at this point in time. A test that measures NK, T and B cells would probably be more informative (Lymphocyte Subset Panel Test (https://www.findlabtest.com/lab-test/blood-tests-for-heart-disease/lymphocyte-subset-panel-1-quest-7197)).
I hope I understood what you were asking. Let me know if you have any additional information that might be useful. I am always learning new things from you guys. :)
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I've also taken B1 a lot, in different forms, and I found it highly useful. But ... indeed, you can build a tolerance. And I have found that after a while of taking 300 mg a day, I got problems breathing. As in: I had to think about breathing, otherwise it felt like my body/brain just didn't do it automatically. Quite scary. At one point I was afraid to go to sleep. Fortunately, all turned out well, but I'm more careful with B1 now.
It's a common problem on the DINET forum: ''Since last summer I have had a hard time breathing on and off. Some days it feels like my body is not breathing on its own.'' (https://www.dinet.org/forums/topic/23531-weird-breathing-symptom/)
Some other note I want to add, is that my slightly elevated 11b-PGF2-alpha could be due to increased AA production. If you take a look at the AA precursors you will end up at lipids. Perhaps there is something wrong with lipid metabolism.
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Thank you Nanna. I am going to an immunogolist within a month. I hope he will do more blood tests. I will report in the blood test topic.
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Unnecessary to re-play a huge post just to report an upcoming Dr visit.
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I think I will be pointing my muonic cannon towards Chile today 8).
(https://c8.alamy.com/comp/BRBD33/old-cannon-on-the-battlements-of-castillo-hidalgo-on-santa-lucia-hill-BRBD33.jpg)
Pointed towards Santiago, Chile
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Hi taurusthree, each dose listed in the original post is per serving. So SAMe 2x(200mg) = 400mg per day. I hope that helps.
Alpha-GPC for example (if chosen as the methyl donor), is currently listed as to be taken in 1.2g dosage. So is it 2x 1.2g = 2.4g? I doubt it, since later in the first post you suggest to work your way up to a twice daily dose at 600mg over the course of one week.
And the latter, I assume, is the final dosage of Alpha-GPC.
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And the latter, I assume, is the final dosage of Alpha-GPC.
Hi taurusthree,
Yes, you are correct! 600mg 2 times per day = 1.2g per day. I am sorry for my poor communication skills. Since this is a common question, I have corrected this in the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497). Also please see this conversation on Alpha-GPC for more details (post (https://poiscenter.com/forums/index.php?topic=2502.msg22791;topicseen#msg22791)). Thanks :)
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Thanks for clarifications!
Almost 3 weeks on the daily total intake of below:
Vitamin B6 - 10mg;
Methylfolate - 1000mcg (will going to cut down the intake soon, currently have deficiency);
Vitamin B12 - 1000mcg;
SAM-e - 400mg;
Vitamin D - 5000IU (will going to cut down the intake soon, currently have deficiency);
Betaine - 1.5g (going to double the dose);
Vitamin C (1000mg) (can probably be beneficial for my joints and may support the immune system);
My story:
26, male. I have (and probably always had) POIS (mild - 1st day: IBS, watery eyes, random itching, brain fog and other cognitive issues; 2nd day: cognitive issues only), trio of [MCAS-POTS-hEDS] (probably inherited from maternal side), ADHD (seems to be distinctly inherited from paternal side), beta-Thalassemia minor (which potentially can contribute to the folate deficiency), allergies.
For more than a year was taking 25mg of SSRI Sertraline (which magically cured my chronic rhinitis, also helped me with my oversaturated emotions, reduced POIS by half, and overall gave me an energy). Didn't try stimulants for my ADHD, since those are banned in my country.
In 2017 I did a test for folate and homocysteine because Promethease suggested I have 2 of the MTHFR mutations (heterozygous). Though I am sceptical about the MTHFR stuff I decided to give a try. Everything was within the normal range. However a month ago the same test revealed I have low folate levels and pretty high homocysteine. My guess is - the activating antidepressant caused that. Also, recently discovered I have low levels of Vitamin D.
So I saw your post and decided to try the stack. 3 weeks after I can report the following:
1. POIS is way milder, mostly cognitive symptoms (could be my ADHD);
2. Gum bleeding during washing my teeth stopped (special thanks for this, I was really upsed by that for more than few years);
3. Overall less hEDS related pain (could be related to the antiinflammatory effect of Vitamin D, also to SAM-e/ methylation antidepressant action);
4. Less local infections (including complete elimination of feet fungus).
Your theory (alpha1 receptors overexpression) can potentially explain the following:
a. How SSRI helped with my chronic rhinitis. In my opinion the mechanism is following: [serotonin reuptake] --> [better parasympathetic tone] --> [less sympathetic tone] --> [less alpha1 receptor firing] --> ... --> [less inflammation];
b. The connection between MCAS, POTS and hEDS. So one of the teories is that hEDS-ers have elastic vessels, which don't hold up during the orthostatic stress induced higher heartbeat (which elevates further, which is the manifestation of POTS). Can't this over time potentially cause an overexpression of alpha1 receptors, so the vessels will be supported as much as possible? And this in turn may induce inflammation from slightest elevations of noradernaline - MCAS-ish symptoms.
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Hi taurusthree,
Your stack looks good! But I assume you are skipping the omega-3/CLA portion. That's fine as long as you are improving. I am glad to hear about your results. I also like that you are customizing dosage based on your personal vitamin deficiency. Your post will be helpful for others who may have similar vitamin deficiencies and medical test results.
I thought your explanation of the alpha1-receptor overexpression is brilliantly stated. When I first read your post, I did not know the exact mechanism for how the a1A-adrenergic receptor would become overexpressed. I only knew what the its properties were and the similarities with what is known about POIS. You actually brought up some ideas that I did not think of. For example, your explanation could be similar/related to Hyperadrenergic POTS (https://www.ncbi.nlm.nih.gov/pubmed/21947988). Also, the connection you made to hEDS makes a lot of sense. I will try to explain what I think you are asking/saying. But please add comments and corrections so that I understand fully what you are proposing. I will start from the perspective of POIS, but I assume the following principles could also be applied to Hyperadrenergic POTS, intense excersise or intense fear.
b. The connection between MCAS, POTS and hEDS. So one of the theories is that hEDS-ers have elastic vessels, which don't hold up during the orthostatic stress induced higher heartbeat (which elevates further, which is the manifestation of POTS).
During sexual activity vasodilation increases (for example: erection and sex flush (https://en.wikipedia.org/wiki/Flushing_(physiology)#Sex_flush)). Epinephrine (adrenaline) and norepinephrine (noradrenaline) is released during orgasm to produce ejaculation (Ref (https://en.wikipedia.org/wiki/Alpha-1_adrenergic_receptor#Smooth_muscle)).
(https://i.imgur.com/43RWkMg.png)
Figure from: Specificity of the neuroendocrine response to orgasm during sexual arousal in men. (U Hartmann, et al, 2003) (http://joe.endocrinology-journals.org/content/177/1/57.full.pdf)
This noradrenaline release also causes Increased Heart Rate (IHR) similar to tachycardia. This is a normal part of sex physiology.
(https://i.imgur.com/gn6QkVf.png)
Figure from: Endocrine response to masturbation-induced orgasm in healthy men following a 3-week sexual abstinence (U Hartmann, et al, 2001) (https://www.ncbi.nlm.nih.gov/pubmed/11760788)
If the total blood volume in the body is constant, an increased heart rate (IHR) means that the heart is pumping with more force and producing larger pulses in blood pressure. This IHR puts greater stress on dilated blood vessels than it does on constricted blood vessels.
(http://hyperphysics.phy-astr.gsu.edu/hbase/imgmec/lapl3.gif)
Figure from: HyperPhysics: Capillary Walls (http://hyperphysics.phy-astr.gsu.edu/hbase/ptens3.html)
From the cylinder surface-tension equation (Laplace's Law (http://hyperphysics.phy-astr.gsu.edu/hbase/ptens.html)): T=P*R, increasing the radius R also increases the surface tension stress T. So for a given blood pressure P, vasodilation (larger radius R) produces a higher surface tension stress (T) on the the blood vessel wall than vasoconstriction (smaller radius R). This increased tension can cause shear stress injury to the vasodilated blood vessels called balloon injury.
(http://hyperphysics.phy-astr.gsu.edu/hbase/imgmec/aneu2.gif)
Figure from: HyperPhysics: Danger of Aneurysms (http://hyperphysics.phy-astr.gsu.edu/hbase/ptens3.html)
Can't this over time potentially cause an overexpression of alpha1 receptors, so the vessels will be supported as much as possible?
As you have stated, vasoconstriction supports and protects the vessels. In response to ballon injury, norepinephrine-induced vasoconstriction protects vessels from undergoing more balloon injury than has already occurred.
"This is the first study to demonstrate enhanced adrenergic neurotransmission after balloon injury. The facilitation of adrenergic neurotransmission may be due to increased local concentrations of angiotensin II..." -Vascular Injury Augments Adrenergic Neurotransmission (RC Candipan, et. al.,1994) (https://pdfs.semanticscholar.org/c6c9/39f68c6dbc33e5cf0ba4628c91abf51991b3.pdf)
This may lead to alpha1-receptor over expression (Angiotensin II induces transcription and expression of alpha 1-adrenergic receptors in vascular smooth muscle cells, ZW Hu, et. al., 1994 (https://www.physiology.org/doi/abs/10.1152/ajpheart.1995.268.3.H1006)), This overexpression causes vasoconstriction (reducing the vessel radius R) which results in reduced surface Tension stress (T = P*R, Laplace's Law) at the location of injury.
And this in turn may induce inflammation from slightest elevations of noradernaline - MCAS-ish symptoms.
One side-effect of injury-induced alpha1-receptor over-expression can be chronic inflammation:
"Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the production and release of pro-inflammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alpha1A-adrenoceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alpha1-adrenoceptors to increase the production of the pro-inflammatory cytokine...These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome...Thus, activation of aberrantly-expressed alpha1-adrenoceptors may contribute to chronic inflammation and pain." -Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury (PD Drummond, 2014) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160862/)
One of Dr. Waldinger's POIS studies noted that pre-mature ejaculation seemed common (56%, error=+-7%) among POIS patients being studied (MD Waldinger, et. al., 2011 (https://www.sciencedirect.com/science/article/pii/S174360951533455X)). Ejaculation is caused by norepinephrine binding to the alpha1-Adrenergic receptor (Ref1 (https://en.wikipedia.org/wiki/Alpha-1_adrenergic_receptor#Smooth_muscle), Ref2 (https://www.ncbi.nlm.nih.gov/pubmed/17603543)). If there is vascular or smooth muscle injury in the reproductive system causing alpha1A-receptor overexpression, this could explain the pre-mature ejaculation symptoms observed by Dr. Waldinger.
It is an interesting coincidence that exercise causes vasodilation partly by down regulating the alpha1-adrenergic receptor.
"a1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, a2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity."
-Exercise attenuates alpha-adrenergic-receptor responsiveness in skeletal muscle vasculature (JB Buckwalter, et. al., 2001) (https://www.ncbi.nlm.nih.gov/pubmed/11133908)
Exercise and fear also produce IHR by releasing epinephrine (adrenalin) and norepinephrine.
If this could explain parts of the POIS-trigger, I still would have a few questions:
- Where is the vascular/balloon injury located?
- What caused the original injury?
- Why does the injury not heal now?
In terms of question 1, POIS symptoms are top-bottom asymmetric in everyone but also left-right asymmetric in some. So the inability to heal properly would have to be localized to specific vessels in the body, while not affecting healing in other blood vessel locations. I suspect that the answers to questions 2 and 3 are the same. Whatever would cause the original injury is also probably keeping it from healing, unless the original injury was a random event.
If you have any corrections or other thoughts, please share. That was interesting!
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Another nice finding from you, Nanna1.
If chronic injury to blood vessels is causing inflammation the most likely place is likely to be the gut vessels.
Most of us have gut problems upon orgasm and it takes a while to get healed and it never heals completely.
Glutamine,aloe juice/jel, change in diet and gut healing foods helps many of us.
So if there is some unhealed inflammation, most likely it should be in the blood vessels of the gut.
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Yeah , it could be a link with gut vesels, Muon posted link of people with
dysautonomia, its tightly conected to our symtopmes like pots etc,
and there some people is diagnosed with stomach aneurism, could be
posible that some of us hawe it, beside odher gut isues.
https://poiscenter.com/forums/index.php?topic=1417.msg13114;topicseen#msg1311
Pois damage our nerwes, cronic inflamation,
that folow systematic disbalance, gut mobility not
working, lack of nutrinents, thats why b vitamins works for some...
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Good discussion guys!
I wonder do Habibou's tests correlate with this theory?
This theory has lot of sens for me , but my adrenalin results are actually really low... ! :)
I will post again my neurotransmitters results :
January 2011
Blood :
-adrenaline <0.50 nmol/l < 1.00
-noradrenaline 8.53 nmol/l < 4.00 1443 ng/l < 675
-dopamine <0.50 nmol/l <1.00
Unrina during 24h :
-adrenaline 0.02 umol/l < 0.10
-noradrenaline 0.42 umol/l < 0.50
-dopamine 1.34 umol/l < 3.00
All the blood tests were done 2 hours after an O.
The red standards are the unusual ones !
January 2012 :
ONLY Urina test, morning 10 hours after an O:
DOPA 91.50 ug/g (160 - 240)
34DOPAC 0.40 mg/g (0.70 - 4.00)
HVA 1.90 mg/g (2.43 - 5.20)
NORADRENALIN 10.30 ug/g (15.70 - 34.30)
MHPG 1.50 mg/g (1.38 - 4.15)
VMA 1.60 mg/g (2.10 - 3.85)
ADRENALIN 0.98 ug/g (1.27 - 6.10)
SEROTONIN 62.40 ug/l (61.50 - 116.80)
5HIAA 2.30 mg/g (2.03 - 4.26)
HVA5HIAA 0.83 (1.25 - 2.56)
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I guess alpha-1 blockers should test if this theory holds merit.
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Good discussion guys!
I wonder do Habibou's tests correlate with this theory?
Good question! The main thing that stands out to me from Habibou's test are his high norepinephrine levels in the blood test 2 hours after orgasm.
January 2011
Blood :
-adrenaline <0.50 nmol/l < 1.00
-noradrenaline 8.53 nmol/l < 4.00 1443 ng/l < 675
-dopamine <0.50 nmol/l <1.00
Neurotransmitters are released in an activity dependent manner depending on what you are doing or thinking. So the levels should rise and fall (fluctuate) fairly quickly. Norepinephrine levels should not be elevated for two whole hours. Maybe the levels fell right after orgasm but then rose again right before the blood test. I started a thread that shows the endocrine response for these neurotransmitters here (Neuroendocrine responses to arousal and orgasm (https://poiscenter.com/forums/index.php?topic=2900.msg26917#msg26917)).
Assuming that his norepinephrine levels remained elevated for at least 2 hours, one way of interpreting Habibou's neurotransmitter test (https://poiscenter.com/forums/index.php?topic=508.msg6851#msg6851) is that he has reduced functioning of his Aldehyde dehydrogenase (ALDH) enzyme (see dopamine degradation pathway, DOPAC, HVA (https://upload.wikimedia.org/wikipedia/commons/e/e7/Dopamine_degradation.svg)). I would rule out monoamine oxidase (MAO) dysfunction because his serotonin and 5HIAA are normal. I would also rule out catechol-O-methyltransferase (COMT) dysfunction because his DOPAC levels are low and his MHPG is normal. DOPAC does not depend on COMT (diagram1 (https://upload.wikimedia.org/wikipedia/commons/e/e7/Dopamine_degradation.svg)) but MHPG does diagram2 (https://commons.wikimedia.org/wiki/File:Noradrenaline_breakdown.svg)). The diagram below shows the enzymes responsible for the 3-Methoxy-4-hydroxyphenylglycol (MHPG) and Vanillylmandelic acid (VMA) parameters in his urine test:
(https://upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Noradrenaline_breakdown.svg/500px-Noradrenaline_breakdown.svg.png)
Decreased ALDH is most common among southeast Asians and is responsible for Asian Flush (https://www.youtube.com/watch?v=G6717bNakuA). I have a friend that goes through this every time they drink alcohol. This might explain his high blood norepinephrine levels, and it could also explain his low urine DOPAC, VMA, HVA and HVA:5HIAA ratio.
Since COMT is a methyltransferase, taking a methylation stack (SAMe, folate, lecithin, etc...) might help remove dopamine metabolites quicker. I don't have an explanation for Habibou's low urine epinephrine and norepinephrine levels, but there are many other neurotransmitter metabolites that are not measured in his test. Also it is important to remember that urine is bodily waste. I could be wrong, but I don't think that urine levels accurately describe what is going on in the blood as much as a blood test.
In terms of the idea Taurusthree shared and I wrote about where alpha1-adrenergic receptors are over-expressed to support/protect the blood vessels through vasoconstriction, it seems that inhibiting the alpha1-receptor with an alpha-blocker would cause additional injury to the vessel. When orgasm happens, alpha1-dependent vasoconstriction at the site of injury should occur at the same time as the increased heart rate/blood pressure because norepinephrine levels control both these events. Moreover, the amount of vasoconstriction should be in proportion to the heart rate because both of these are in proportion to norepinephrine levels. So, in theory, the alpha1-receptor should be protective and vasoconstriction should be protective. Relevant bio-markers to test if there is vascular balloon injury are angiotensin II (https://pubchem.ncbi.nlm.nih.gov/compound/angiotensin_ii#section=Top), endothelin-1 (https://en.wikipedia.org/wiki/Endothelin_1) and possibly creatine kinase.
However, when I get blood test (medical test), the nurse sticks a needle in my arm and punctures a vein in order to extract the blood. My vein heals quickly (<24 hours) without any POIS or systemic immune reaction. So I do not think that there is anything global wrong with my arteries or veins. But if alpha1-receptor overexpression is causing POIS problems, it could be a possibility that norepinephrine and alpha1 are also triggering something else that is locally latent in that portion of the blood vessel and preventing proper healing of the vessel. This is the reason that I asked the questions:
If this could explain parts of the POIS-trigger, I still would have a few questions:
- Where is the vascular/balloon injury located?
- What caused the original injury?
- Why does the injury not heal now?
I don't think this thread is the best place to discuss a lot of detailed theory since many POISers here are rightfully interested in stacks. So I would prefer to discuss more detailed theories of POIS on other threads. Thanks Nas for your question!
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Thanks for the detailed reply Nanna, as usual.
If you want start another thread and we can discuss this all right there. I don't to do it my self since I don't even know what would I call that thread.
I guess when it comes to the Alpha-1 blocker inquiry, Taurusthree mentioned that this constant over-expression is what leads to these inflammatory symptoms; MCAS-like symptoms. So perhaps the injury itself won't heal but the systematic symptoms can be better dealt with? Maybe I'll try an alpha-1 blocker and see if it does anything at all.
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Nanna, I also wish in the future if you tack this, this is written by Waldinger:
''The lack of a local genital skin reaction after ejaculation, but the occurrence of multiple complaints after ejaculation, and the findings of the hyposensitization treatment suggest that in POIS immunologic reactions occur due to repeated close contact during ejaculation between seminal peptides and circulating T-lymphcytes. This leads to a systemic reaction with multiple physical and cognitive complaints.''
I think we have theorized many things that POIS can be. But we rarely paid attention to what Waldinger himself thinks. After all he worked closer with POIS than anyone of us.
I feel like this comment is his theory but incredibly summarized, and I wish it gets better explained. If POIS is actually an auto-immune disease, then how do we get systematic symptoms instead of localized ones?
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Do you guys think it should work on Emotional symptoms like Social Anxiety? I get this for a couple of days after O, I'm totally less self-confident then...
What do you think guys?
Nanna1? ...
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Hi Whateverestest,
I also used to have social anxiety that occurred after sexual activity (during POIS). I did not associate it with POIS though. My symptoms are listed here (post (https://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039)). I do not see the benefit of focusing on individual symptoms. Symptoms correlate well with the location of a disease in the body, but they do not correlate well with actual causes of disease. For example, if someone gets:
(1) hit in the knee cap with a hammer or (2) develops cancer in the knee cap or (3) gets an infection in the knee cap, the symptoms will be mostly the same (pain in the knee, inflammation in the knee, immune cell activation in the knee, etc...). Even if there are some differences in symptoms, most of the symptoms will still be a function of the location in the body and not unique to an actual cause. So treating disease based on symptoms can be tricky. In my opinion, medical test give a more accurate tool for narrowing down potential causes and determining which treatments may be helpful (see medical test patterns post (https://poiscenter.com/forums/index.php?topic=2695.msg24788#msg24788)).
One way around this could be to seek the counsel of a professional psychiatrist. They may be able to perform test to determine why social anxiety occurs after sexual activity and give you options for treatment. Social anxiety can sometimes be caused by a depletion of GABA and dopamine. The depletion of certain neurotransmitters (https://poiscenter.com/forums/index.php?topic=2900.msg26917#msg26917) can occur after porn use.
This is what porn does to your dopamine levels.
(https://steemitimages.com/DQmeFcNBbBHXLGSmCDM8HndYj4j33DKKtojvrYnrCsyQ4UC/DopamineSurges.jpeg)
While porn is being viewed, dopamine levels remain elevated. But when the porn goes off, dopamine tanks. It's called the Coolidge effect (http://www.heretical.com/wilson/coolidge.html).
(https://oceanrecoverycentre.com/wp-content/uploads/2016/07/9.-Reward.png)
In my case, stopping porn cured my orgasm-induced social anxiety, but it did not cure my POIS. I do not think that POIS is caused by porn addiction. People develop POIS even when there is no porn use, and your anxiety may have nothing to do with viewing pornography. But I think that porn addiction (a known cause of social anxiety, link1 (https://en.wikipedia.org/wiki/Pornography_addiction), link2 (https://www.addictioncenter.com/community/signs-of-porn-addiction/)) should be ruled out before experimenting with supplements and drugs. From my experience and from reading post by others, it seems that POIS can aggravate other unrelated diseases. There are many post on the forum where POISers have multiple unrelated diseases (i.e. fungal infection, food allergy, physical injury, general stress, etc...). Getting professional treatment for (or curing) the other diseases may also reduce some of the symptoms experienced during POIS, even if it does not cure or treat POIS directly.
In general, I think that the best starting point for eliminating POIS symptoms is maintaining good health. This is not what most people want to hear but it is true. So healthy diet, drinking water, getting adequate sleep and reducing emotional stress. It wasn't until I started taking the POIS Cascade stack (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) that I could exercise without getting sick, but now I exercise 2 to 3 times a week.
The two stacks in the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) are independently focused on stopping the inflammatory cascade (arachidonic acid cascade) which I believe triggers POIS. These stacks do not treat symptoms, they only prevent symptoms. So waiting to take the Betaherpesvirinae stack after an orgasm will not help much. It has to be taken 2 hours before POIS is triggered to prevent the trigger from occurring. For me this also prevented all the symptoms. The instructions for each stack is very specific. And the timing and dosing information is important for the effectiveness of each stack (timing post (https://poiscenter.com/forums/index.php?topic=2502.msg26349#msg26349)).
Note: You should check with your medical doctor to make sure that these or other supplements do not interfere with any drugs you may be taking. Also check with your physician to see if any pre-existing health condition prevents you from taking these supplements/drugs.
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Hi Whateverestest,
I also used to have social anxiety that occurred after sexual activity (during POIS). I did not associate it with POIS though. My symptoms are listed here (post (https://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039)).
Did it just occure after sexual activity or orgasm? Did it just occure or last for the next days? Because in my case it lasts for 6-8 days after orgasm. And in my case I could have sex on and on as long as I didn't have orgasm (or come very very close to it, if that's possible:P) I wouldn't have any symptoms at all..
In my case, stopping porn cured my orgasm-induced social anxiety, but it did not cure my POIS. I do not think that POIS is caused by porn addiction. People develop POIS even when there is no porn use, and your anxiety may have nothing to do with viewing pornography. But I think that porn addiction (a known cause of social anxiety, link1 (https://en.wikipedia.org/wiki/Pornography_addiction), link2 (https://www.addictioncenter.com/community/signs-of-porn-addiction/)) should be ruled out before experimenting with supplements and drugs.
In my case it didn't. I still will have anxiety even after NE. Currently I technically don't watch porn. It sometimes happens though, but only cause I developed some kind of IMO, "obsesive-compulsive-like behaviour" that after having orgasm I masturbate 1-2 more times. Don't ask me why, maybe it's partially because that relieves me from the tension (and fear of next days) caused by previous Orgasm, maybe it's an excuse that I keep giving myself "if I'm gonna feel bad anyways...".
But anyways. I drastically reduced watching porn quite some time ago (just because of my point of view on that matter), and that didn't help. Mostly I get orgasm from NE or when by myself, (no porn) and that triggers anxiety as well.
Symptoms correlate well with the location of a disease in the body, but they do not correlate well with actual causes of disease. For example, if someone gets:
(1) hit in the knee cap with a hammer or (2) develops cancer in the knee cap or (3) gets an infection in the knee cap, the symptoms will be mostly the same (pain in the knee, inflammation in the knee, immune cell activation in the knee, etc...). Even if there are some differences in symptoms, most of the symptoms will still be a function of the location in the body and not unique to an actual cause.
That brings me hope that there actually is a point in testing stacks that people and you suggest here and there even if my POIS symptoms vary drastically. I will continue trying. Thanks.
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Regarding porn, masturbation and the connection with anxiety, perhaps this (long) story can provide some guidance:
https://101nootropics.com/nofap-benefits-and-advice/
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Hi everybody,
I'm Italian, so for me it's very difficult to explain...
I've tried many times to register and finally I have done.
nanna1, your theory is very interesting but I can't understand the red line to xanthine oxidase.
I ask you because I have high serum uric acid, and I have always wondered if there was a link with POIS, since I haven't read nothing about uric acid in this forum.
Thank you!
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I also add some details...
I think that POIS is only a symptom of a problem.
I say this because I have POIS symptoms also if I abstain from sex and if I'm stressed or do exercise (as I also read here), even if to a much lesser degree...
For me, and I don't know if you have already discussed, there are some important point:
1. In your stack there is a big use of B vitamins. I use them and feel a big improvement BUT after some day of use I feel very irritability and anxious (it's a tipe of anxiety different from that of POIS). I don't know what vitamin create this problem, I can only tell that my B12 is always correct in my exams, also homocysteine.
Same effect derives from the use of tryptophan and zinc, I have bad nightmares from them (after some day of use, though)
2. From my last fatty acids test, I have normal omega 3 even if I don't eat fish. The deficient one is omega 6 LA and GLA, which I read are very important for PGE1 formation. Can POIS be a PGE1 deficiency that also create imbalance with PGE2? I haven't read in your stack the use of Borrage or Evening primrose which can be beneficial (mine is only an hypothesis)
The symptoms that link my problem with GLA (which is beneficial for) are:
-seborrheic dermatitis, eczema and atopic dermatitis
-dry eyes
-bleeding gum
-migraine
Does anybody have these symptoms?
Omega 3 will increase only PGE3, not PGE1
3. I have, as I said, elevated uric acid. There are my values:
-7,6 mg/ dL [3,5 - 7,2] June 2018
-8,0 mg/ dL [3,5 - 7,2] February 2019
Since Xanthine Oxidase of your theory is an enzyme that produces uric acid, what is the relation with POIS in your theory?
4. In addition to POIS, I have:
- neck and back stiffness
- vision problems like visual snow and object trails (especially at night)
- muscle spams
- migraine
- anxiety even if I abstain from sex
The anxiety is very high since I don't know if my symptoms are linked only with anxiety (and POIS) or something else...
Finally, two very big problems:
DIGESTION
I feel like I cannot digest food. After 30 minutes from meal, I feel bloated and have flashes. After 3-4 hours I have to belch and sometime this happen also at night with a little bit of tachycardia.
EXERCISE and STRESS
I can't exercise or stand the minimum stress since I start to sweat and if this happen I have panic attacks, fatigue and impaired digestion for days.
When you said the exercise cause you problems, do you find any correlation with mine?
One last question, what does b. f. stand for?
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Brain Fog. Thanks for posting Allesandro84
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Hi Alessandro84,
I think that POIS is only a symptom of a problem.
I say this because I have POIS symptoms also if I abstain from sex and if I'm stressed or do exercise (as I also read here), even if to a much lesser degree...
I agree with this. POIS-like symptoms can be caused by other stressful activities (see medical test patterns: non-arousal triggers for POIS-like symptoms (http://medical test patterns: non-arousal triggers for POIS-like symptoms)). I think that "The Cause" of POIS can also cause other diseases. I gave a hypothesis for a possible cause here (POIS as a location-specific herpes infection (https://poiscenter.com/forums/index.php?topic=2683.msg23766#msg23766)). There is also a literature review of possible causes that others have proposed here (POIS literature review (https://poiscenter.com/forums/index.php?topic=2683.msg23777#msg23777))
1. In your stack there is a big use of B vitamins. I use them and feel a big improvement BUT after some day of use I feel very irritability and anxious (it's a type of anxiety different from that of POIS). I don't know what vitamin create this problem, I can only tell that my B12 is always correct in my exams, also homocysteine.
Same effect derives from the use of tryptophan and zinc, I have bad nightmares from them (after some day of use, though)
I agree that POIS is not caused by under-methylation"
methylation
--3 of us have normal folate levels (certainlypois2 (http://poiscenter.com/forums/index.php?topic=2684.msg24954#msg24954), quotz, BluesBrother)
--3 of us have normal homocysteine levels (BluesBrother, nanna1, jakov).
But a slight over-methylation appears to provide some benefit. I do not know how that benefit occurs. It could be through a repression of the arachidonic acid (inflammatory) cascade or a decrease in DNA replication. But these are guesses. The irritability/anxiety/nightmares may be from an increase in neurotransmitters (i.e. serotonin). From my experience, Alpha-GPC generally produces better neurotransmitter balance than most methyl-donors.
2. From my last fatty acids test, I have normal omega 3 even if I don't eat fish. The deficient one is omega 6 LA and GLA, which I read are very important for PGE1 formation. Can POIS be a PGE1 deficiency that also create imbalance with PGE2? I haven't read in your stack the use of Borrage or Evening primrose which can be beneficial (mine is only an hypothesis)
The symptoms that link my problem with GLA (which is beneficial for) are:
Thanks for sharing your test info! For the hypothesis that I proposed, the key is to lower arachidonic acid (but not all omega 6). Plants produce omega 6 (LA and GLA) but they do not produce arachidonic acid (AA). The body cannot produce (from LA) any where near the amount of AA that you absorb from meat. So most of the AA in the body of omnivores comes from meat consumption through the stomach. If you are sensitive to AA, them your stomach might tell you. Once AA has been removed from the diet, then omega-3s can replace AA (see omega-3 post (https://poiscenter.com/forums/index.php?topic=2502.msg25312#msg25312)). I do not know how the ratios of different prostaglandins are balanced. That is beyond my current understanding, but your ideas about PGE1:PGE2:PGE3 seem interesting :)
-seborrheic dermatitis, eczema and atopic dermatitis
Whenever I had skin problems like these (not often), I would use tea tree oil or bergamot oil applied topically to the skin. Initially, they will irritate the top layer of the skin. But most of what this is is exfoliation of dead, stressed or infected skin. For me, after the top skin layer exfoliated, the skin irritation went away and they started having a cooling/anti-inflammatory type effect (less bumps, itch and pains). These two essential oils are milder than most and have anti-viral and anti-bacterial (antiseptic) properties. Some oils like cinnamon or oregano cannot be applied to the skin without incurring chemical burns. For any essential oil, keep them away from your eyes and avoid rinsing with water because that increases the irritation and exfoliation.
3. I have, as I said, elevated uric acid. There are my values:
-7,6 mg/ dL [3,5 - 7,2] June 2018
-8,0 mg/ dL [3,5 - 7,2] February 2019
Since Xanthine Oxidase of your theory is an enzyme that produces uric acid, what is the relation with POIS in your theory?
Outside of the mitochondria, Xanthine Oxidase is the main producer of superoxide O2-. And superoxide is a cofactor for most (if not all) inflammatory/oxidative enzymes (see Inflammation and disease (https://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769)).
XO is also responsible for converting DNA base acids (adenine, base-A, and guanine, base-G) into uric acid. This depletes the pool of bases needed for DNA and RNA replication. So the immune system can up-regulate XO to stop pathogens from replicating their DNA within the cell. However, this up-regulation of XO is still a highly destructive and inflammatory situation.
4. In addition to POIS, I have:
- neck and back stiffness
- vision problems like visual snow and object trails (especially at night)
- muscle spams
- migraine
- anxiety even if I abstain from sex...
...Finally, two very big problems:
DIGESTION
I feel like I cannot digest food. After 30 minutes from meal, I feel bloated and have flashes. After 3-4 hours I have to belch and sometime this happen also at night with a little bit of tachycardia.
EXERCISE and STRESS
I can't exercise or stand the minimum stress since I start to sweat and if this happen I have panic attacks, fatigue and impaired digestion for days.
When you said the exercise cause you problems, do you find any correlation with mine?
I've had all these problems prior to finding relief from my stack. But instead of migraines, I had hemicrania continua (https://poiscenter.com/forums/index.php?topic=2683.msg24158#msg24158), tension headaches and post-coital headaches (https://www.mayoclinic.org/diseases-conditions/sex-headaches/symptoms-causes/syc-20377477). But I think as my immune system improved, the exercise/muscle related symptoms and vision problems went away. I am now a big fan of boosting the immune system through diet, sleep, supplements, etc... I think the anxiety and irritability I had was partly related to porn use and the resultant dopamine depletion. When I stopped porn, those symptoms slowly disappeared. Others may experience anxiety and/or irritability for non-porn reasons like genetics or brain infections. So each person is different.
Let me know if you have questions, comments or new ideas. I am always willing to learn.
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Thanks, nanna1!
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Hi Nanna
I have some personal questions about the stack. Would greatly appreciate it if you could answer them.
1. When I added methylfolate I get brain fog symptoms and pressure on both sides of my head should I try normal folic acid or just leave it out? I have low folate in my bloods.
2. I have tried your stack in the past but have stopped due to getting intense anger from the alpha gpc. And before I started taking it I was very emotionally numb with no anger what so ever.
3. The stack also seems to make my brain fog after either hot or cold showers a lot worse than usual
4. After a few days after taking alpha gpc I wake up early in the mornings with bad lower abdominal bladder/intestinal pain and needing to pee badly, after reading what you've said in here I reckon maybe I have some type of damage to blood vessels in my lower abdomen pelvic area. My veins in the area also darken a lot after taking the stack. I know that people who have Urinary urgency take anti cholinergic to stop that urgency.
5. I missed out CLA by accident is this an important part of the stack?
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1 more thing I think the sam e makes me a little foggy, less sociable and more awkward but I need to test this further and the same thing happens when I have too much alpha gpc - 300mg seems to work better than 600mg. Also I know this isn't that relevant but why does my sam e smell like you haven't washed your balls for a week. Do they all smell like that lol or did I just buy from a bad supplier.
Currently it seems to work best with b12 100mcg, b6 10mcg, alpha gpc3/600, vitamin d3 1000iu and fish oil. I know folate and sam e are an important part of the cycle so I'm not sure why they seem to make things worse.
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Yes speech problems 100% start when sam e is added - maybe i will try with 100mg instead of 200mg and if still bad then I will stop sam e.
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Thanks for posting, IWBT
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4. After a few days after taking alpha gpc I wake up early in the mornings with bad lower abdominal bladder/intestinal pain and needing to pee badly, after reading what you've said in here I reckon maybe I have some type of damage to blood vessels in my lower abdomen pelvic area. My veins in the area also darken a lot after taking the stack. I know that people who have Urinary urgency take anti cholinergic to stop that urgency.
Hi Iwillbeatthis,
Sorry for the late reply. Several of the symptoms you mention (waking up early, brain fog) could be due to taking the methyl donors too late in the evening. If you take SAMe-methylfolate-alphaGPC within 6 hours of your normal bedtime, they could disturb your sleep quality (shorten sleep time). This is because these methyl donors increase neurotransmitters like acetylcholine, dopamine, noreadrenaline... Needing to pee could also be a result of excess norepinephrine (NORE) production during sleep since NORE can contract the bladder and other smooth muscles like the intestinal walls. Sometimes when I have an orgasm, that will put me to sleep independent of when I take the methyl donors. You can take 5-HTP to offset the sleep disturbing effect, but I would just take the methyl donors earlier in the day so that you get good sleep. Taking the methyl donors in the morning (and afternoon) actually helps my sleep probably because of the increased serotonin. There could be other non-POIS things affecting the way the methyl donors are affecting you, but my guess is that taking them too late in the day is disturbing your sleep and causing an increase in neurotransmitters during sleep. Poor sleep produces other side-effects. I could be wrong, so listen to your body and do what is best for you. ;)
5. I missed out CLA by accident is this an important part of the stack?
CLA seems to have a synergistic effect with omega-3. I can take less omega-3 when I take CLA. But my guess is that they work together to reduce omega-6 arachidonic acid (AA). Taking CLA and omega-3 (1), reducing AA consumption from food (2) and blocking COX (3) are all ways of preventing excess PGE2 formation. The goal is to reduce PGE2. Let me know if this answered your question or if you have other comments.
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Iwillbeatthis, these are just my opinions, from what you mention is indicating that you have an auto-immune thyroid disorder. While SamE is the sweetest anti-depressant for me (since I'm hypothyroid suspect) you seem to switch between hypo and hyper thyroid states. During a hyper state, thyroid increases sensitivity of catechlomines, sensitivity to heat etc while in hypo-state you get reduced sensitivity to catechlomines, increased sensitivity to cold etc. So my point is, for a person swinging into hyper, SamE will make your situation worse i.e. bouts of excessive dopamine. I would suggest an Endocrinologist and get a full thyroid panel that includes Thyroid antibodies panel, free T3, Reverse T3. The samE I used was smell neutral so it could be the formulation you purchased. You might also want to discuss PABA with your doc since you have trouble with folate. Question: Do you have frequent white film or lesions on any part of your mucosa, oral epithelium, tongue etc?
Hi Nanna
I have some personal questions about the stack. Would greatly appreciate it if you could answer them.
1. When I added methylfolate I get brain fog symptoms and pressure on both sides of my head should I try normal folic acid or just leave it out? I have low folate in my bloods.
2. I have tried your stack in the past but have stopped due to getting intense anger from the alpha gpc. And before I started taking it I was very emotionally numb with no anger what so ever.
3. The stack also seems to make my brain fog after either hot or cold showers a lot worse than usual
4. After a few days after taking alpha gpc I wake up early in the mornings with bad lower abdominal bladder/intestinal pain and needing to pee badly, after reading what you've said in here I reckon maybe I have some type of damage to blood vessels in my lower abdomen pelvic area. My veins in the area also darken a lot after taking the stack. I know that people who have Urinary urgency take anti cholinergic to stop that urgency.
5. I missed out CLA by accident is this an important part of the stack?
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Thanks, nanna & swell!
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POIS is most likely a mast cell activation disorder.
Mast cells are primitive cells of the immune system which act as “sentinels,” present in all tissues but standing guard most prominently at the body's environmental interfaces, e.g. the skin, the gastrointestinal tract, the respiratory tract and the genitourinary tract. Unlike lymphocytes, which have great specificity, mast cells use non-specific chemical mediators as their dominant mechanism of attack against foreign invaders (e.g. parasites). More than 200 different mast cell mediators have been identified, including histamine, tryptase, heparin, prostaglandins and leukotrienes.
Unlike allergies, which involve specific IgE-mediated activation of mast cells, mast cells in MCAS are activated inappropriately by specific and non-specific triggers, such as positive or negative emotional or physical stress, extremes of temperature or temperature or barometric pressure change, environmental chemicals, alcohol, high histamine foods, odors, physical stimuli (e.g. pressure from a tourniquet), drugs, and the non-drug ingredients (excipients) in medication products. Since mast cells are present in all organs, and since their chemical mediators enter the bloodstream, inappropriate mast cell activation can produce a large number of signs and symptoms that may vary and occur in a fluctuating pattern, often creating a complex clinical picture. Like most diseases, MCAS exists on a spectrum, ranging from very mild to extremely severe, and it has been estimated to affect up to 17% of the population.
Symptoms of MCAS may be acute and/or chronic. Skin flushing, itching, fleeting rashes and hives are very common, but not all patients have grossly obvious cutaneous manifestations. Other common symptoms include bone, muscle, joint and/or neuropathic pain; paresthesias; gastroesophageal reflux; abdominal pain; nausea/vomiting; bowel motility issues (gastroparesis and/or diarrhea alternating with constipation), presyncope/syncope, heart rate and/or blood pressure lability, chest pain, dyspnea (often subtle, typically described as an occasional brief inability to take a deep breath), unexplained weight loss or gain (which may be significant), anxiety, depression, mood lability, cognitive dysfunction, sleep disturbance, lethargy, fatigue, malaise, fevers, night sweats, headache and vertigo. Many patients experience mast cell “flares” or “spells,” but more severely affected patients also have chronic symptoms due to constitutive mediator release aside from mediator release related to aberrant reactivity. Prior to adulthood, patients with MCAS often initially enjoy symptom-free intervals interspersed amongst symptomatic periods. Over time, symptom-free intervals shorten, and finally symptoms become chronic with an intensity which fluctuates, but with an overall trend toward steadily increasing severity. An increase in disease severity often follows major stress. Mast cells are also intimately involved in growth regulation.
Patients with MCAS have often experienced a lifetime of multi-system unwellness with broad themes of inflammation, allergy, and disordered growth. For most MCAS patients, signs of the disease first emerge in childhood (median age at symptom onset is 9 years), but there is an average delay in diagnosis of MCAS of 30 years In one evolving model, MCAS increasingly is being suspected to arise proximately from mutations in one or more mast cell regulatory genes, and these mutations – usually somatic, heterozygous, and multiple – themselves likely emerge due to complex interactions among other mutations which are germline (i.e., inborn) and both genetic and epigenetic6, 7. Stressor-induced cytokine storms, too, may significantly impact these interactions and the development of the consequent somatic mutations (that is, mutations which are acquired, not inborn, but often beginning relatively early in life). MCAS may also occur secondary to an underlying allergic, infectious, immunodeficiency or an autoimmune disorder.
Most of the pois treatment prepacks work largely by blocking the mast cell activaton or histamine release.
Niacin
http://getwellstaywellathome.com/blog/2015/06/seasonal-allergies-and-the-niacin-flush/
Taurine
https://www.ncbi.nlm.nih.gov/pubmed/28694089
TRT
https://journals.aace.com/doi/pdf/10.4158/EP161530.CR
Relief with Antihistamines, flavanoids in fenugreek&garlic, oral corticosteroids ,methylation support,pre-pack with IDO/TDO/NMDAr blockers+ anti-oxidants and gluten free diet etc all point to mast cell activation disorder.
Most of our members get relief with one of the above mentioned ways which also fits with MCAD where everyone has individual triggers and get relief with personalised treatment.
So POIS is most likely to be MCAD triggered by mast cells present in the urinary tract and causing systemic inflammation which many a time crosses blood brain barrier and results in neural inflammation.
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I also thought that Aswinpras, but then I tried almost all methods to block histamine release and stabilize Mast Cells. MCAD is most definitely not the cause of my POIS.
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I also thought that Aswinpras, but then I tried almost all methods to block histamine release and stabilize Mast Cells. MCAD is most definitely not the cause of my POIS.
Hi Nas
Mast cell activation disorders are very hard to treat as per my Pulmonologist when I asked him about it during my last consultation. New drugs and treatments are very expensive and still under experimental stage according to him.
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Hi Nas
Mast cell activation disorders are very hard to treat as per my Pulmonologist when I asked him about it during my last consultation. New drugs and treatments are very expensive and still under experimental stage according to him.
I agree and I went into deep investigation on MCAS and I even joined a MCAS community and after following different treatment choices and talking to many MCAS sufferers I was convinced that I don't have MCAS. I can go into more detail if you want to know how I reached this conclusion if you want.
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Hi Nas
Mast cell activation disorders are very hard to treat as per my Pulmonologist when I asked him about it during my last consultation. New drugs and treatments are very expensive and still under experimental stage according to him.
I agree and I went into deep investigation on MCAS and I even joined a MCAS community and after following different treatment choices and talking to many MCAS sufferers I was convinced that I don't have MCAS. I can go into more detail if you want to know how I reached this conclusion if you want.
Nas just now I've read your trigger for POIS from your earlier posts
"True, perhaps there are different types of POIS, but I can assure you that beside cigarettes, arousal and ejaculation are the only triggers for me. And urethritis and potentially prostatitis are observed after ejaculation in my case. So at least for me, it's looking closer to an autoimmune reaction."
I am not a medical person so I cannot provide you any scientific explanation. So I am just providing my views on your triggers.
Cigarette smoke can trigger MCAS in the respiratory tract for susceptible people and it is well documented. Arousal itself can cause some fluid build up in the urinary tract and can very well activate the mast cells even without ejaculation.
If you've taken treatment for MCAS from a allergist/immunologist and still did not get any relief then it has to be some other problem.
Also note that MCAS are notoriously difficult to treat unless correct medications are given. Even the excipients in a tablet can cause mast cell problems and so extreme care is essential while treating Mast cell activation disorders.
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Cigarette smoke can trigger MCAS in the respiratory tract for susceptible people and it is well documented. Arousal itself can cause some fluid build up in the urinary tract and can very well activate the mast cells even without ejaculation.
If Mast Cells were specifically triggered in the respiratory tract, you would suffer coughing, asthma and phlegm build up; all these do not occur in my case; only neurological symptoms.
Besides the unusual lack of anaphylactic attacks that are associated with MCAS.
Also note that MCAS are notoriously difficult to treat unless correct medications are given. Even the excipients in a tablet can cause mast cell problems and so extreme care is essential while treating Mast cell activation disorders.
From my experience with MCAS sufferers, this occurs usually in dire cases where the MCAS attack is life threatening or unpredictable. When it comes to neurological sufferers of MCAS simple treatment of anti-histamines can bring them their brain back.
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Hi Nas
I don't know why cigarette smoke causes no respiratory symptoms but POIS for you. But smoking can trigger immune response in the gastrointestinal tract and even in liver. If I find any useful info regarding this, surely will update you.
As for as anaphylactic attacks are concerned they happen only for a few allergy sufferers and not for all. I know you must have tried lots and lots of medicines and supplements for MCAS with no success. But still have a look at these links. They contains some useful medical options including LDN.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/
https://casereports.bmj.com/content/2018/bcr-2017-221405
https://www.integrativehealthrichmond.org/single-post/2018/04/17/Diagnosis-and-Treatment-of-MCAS-Mast-Cell-Activation-Syndrome-aka-everything-I-take-do-or-am-exposed-to-makes-me-feel-horrible
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Thanks Aswinpras,
I also like to add the point of scale; you can tell if the medication is effecting the right system if there is reduction is symptoms, even if slight. For example dexamethasone 1mg helps me a lot but not completely. This tells me that I'm hitting the right system, and by increasing the dosage I might get rid of POIS. So if I truly had MCAS, then a simple anti-histamine ( I tried strong ones ) would at least show slight improvement, but they really did near nothing, so that tells me, that I'm not hitting the right system. This is how I judge many of the theories I test when it comes to POIS.
About Anaphylactic shots it seems that almost all MCAS sufferers I talked to suffer from it.
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Hi nanna,
Thanks for sharing such a thoughtful analysis and POIS stacks.
I happen to have a different version of POIS.
A- If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS and they last for 3-4 days. During this time i suffer from brain fog, excessive sleepiness, light headed, excessive sweating, irritated, cognitive impairment, fatigue, muscle weakness and headache/migraine. The more i sleep the sooner i can recover from these symptoms but they still take about 3 days at least although the symptoms become milder as i sleep more.
POIS is not triggered if i sleep at night right after sex. And due to this awkward strange reaction to sex i can not go for sex during day time. I can only have sex at night and sleep right after (in order to avoid POIS)
B- If i orgasm after masturbate, then POIS kicks in within an hour and gets worse the next day and lasts for 3-4 days. Even if i go to sleep right after masturbation/orgasm at night, it still does not help ! I get plenty of sleep yet the next day the symptoms of POIS starts to appear and gets worse the following day and then begin to subside the 3rd day and almost fully disappear by the end of 4th day from masturbation/orgasm. I did experiment few supplements but they either did not work or their effects were very short lived. I was also deficient in vitamin D3 and after taking supplements for it, the POIS symptoms got a little bit better.
In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation? And why do i have to sleep within 20min or so after sex to avoid POIS? And i don't understand why i get so heavily sleepy headed with POIS as if i am drugged and i am literally dragging myself to do daily chores not to mention the anxiety and discomfort that comes with it/pois.
I am thinking of starting your POIS cascade stack for 3-4 weeks while skipping CLA for now. Would you suggest different supplementation and dosage to specifically target my particular situation? Also could you suggest the brands for each supplement (possibly using amazon links)?
I am 38 years old male and have been suffering from pois for more than 10 years or so.
Your insight in this matter is greatly appreciated.
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Hi, Sameer, and welcome to the forum! :)
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Hi Guys,
I'm back with some updated results.
The stack effects were so profound that this method surpasses alternative treatments I tried so far mentioned in this forum. I really didn't anticipate the effects to even last this long, it didn't last for few hours or even few days, it lasted for several weeks symptoms free. If you even read my earlier posts I was able to even o multiple times. My POIS is really pretty bad in terms that I can feel the symptoms without o or any stimulation.
The initial supplements I took were MenthyB12, Folinic Acid and TMG that improved the following symptoms
-Brain fog which encompasses short long term memory
-Anxiety
-Became an extrovert in sense that I wasn't afraid to speak my mind
-Plenty of motivation
-Needed less sleep
-Was able to eat histamine foods
-Able to speak clearly as in no fumble in words
So the effects wore off and no longer works, now everyday I feel lethargic no matter how much sleep I have which I don't have before. I'm not sure what happened and have stopped the supplementation for several weeks now. Those weeks were the best weeks I ever lived in lol. Oh well.
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Itsmel, wery intresing, you are improved yours methaylation and
detox phases of yours body by taking supplement stack you mention.
But after some time, the symptomes are relapsed.
All that remeind me on chronic infection patients wich i mention a lot.
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I happen to have a different version of POIS. If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS and they last for 3-4 days.
It could be that you are too tensed up. I can't find the paper right now, but there is some research that showed that some people with POIS use improper technique during sex, where they tense up their muscles too tightly and apparently this causes issues. Loosening up completely during the act, and during O might solve this.
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What supplements are you guys using to meet the B vitamin requirements in the OP? I got this from Jarrow because it was recommended in the thread:
https://www.jarrow.com/product/661/Methyl_B-12_&_Methyl_Folate_Lemon (https://www.jarrow.com/product/661/Methyl_B-12_&_Methyl_Folate_Lemon)
At 1 mg of B12 it has 41670% of the RDA. I don't like taking that much B12 daily and I don't like the Xylitol in it. Is there anyone else that makes B Vitamins in small amounts? I'd like pills not powders I have to measure if possible.
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Remember to get good quality sleep, LOL! ;D
(https://assets.purple.com/images/jk-studios-hero.jpg)
https://www.youtube.com/watch?v=5XGmJ17pASA&t=0s (https://www.youtube.com/watch?v=5XGmJ17pASA&t=0s)
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What is the reason for adding citrulline malate to the stack?
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What is the reason for adding citrulline malate to the stack?
The short answer is that I tried it and it was effective for what I was trying to do. Citrulline malate works in synergy with caffeine to help correct endothelial dysfunction and the immune related issues that cause vascular problems. I discovered this by accident when trying out different pre-workout supplements. Over time, I believe the caffeine-citrulline combo produced improvement my breathing, vascular function and better blood circulation control. These improvements were long-term and continued even when I stopped taking the supplements. I did not notice any positive effects on vasculature from taking them separately. I later included these two supplements in an immune therapy that I was giving to myself. But I would not take these on a regular basis, only as prepack.
If you are looking for a one-time solution for reducing symptoms, I would say that citrulline will not help much. But citrulline may help increase nitric oxide (NO), help endothelial dysfunction and possibly immunity in the epithelium. So for me it was more of a health/immune-treatment, than a symptom-treatment. I hope this clarifies.
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I have read citrulline turns into arginine in the body. This is likely an oversimplified description. Many people report arginine is like throwing gasoline on a fire for Herpes outbreaks. If you believe, or theorize, POIS has a Herpes connection you may want to check that out.
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I have read citrulline turns into arginine in the body. This is likely an oversimplified description. Many people report arginine is like throwing gasoline on a fire for Herpes outbreaks...
Hi drop247,
Thank you for your question. I agree that it is not good to take pure L-arginine directly. Choosing citrulline malate (an arginine pro-drug) over arginine is very important. Also, I think it is important to only take citrulline malate with a arginase inhibitor like caffeine (see post (https://poiscenter.com/forums/index.php?topic=2695.msg31234#msg31234)). I will explain why the arginase inhibitor matters. The two main enzymes that metabolize arginine are nitric oxide synthase (NOS) and arginase.
NOS produces nitric oxide from L-arginine and this NO production is used by the immune system to fight infection and cancer (among other things). NO produced by eNOS also maintains the elasticity of blood vessels and the health of endothelial cells. NO produced by nNOS is important for brain growth and memory development (Nitric oxide synthases (https://en.wikipedia.org/wiki/Nitric_oxide_synthase)). One alternative to taking arginine prodrugs is to consume vegetable-based nitrates instead. Nitrates convert to NO in the body. Beet juice and spinach powder are good sources of nitrates (link (https://www.ergo-log.com/red-spinach-a-natural-no-booster.html)), but I'm not sure how much of these vegetables you will have to consume to get the equivalent effect as citrulline.
Arginase produces spermine from L-arginine. Spermine suppresses the immune system and prevents immune cells from killing pathogens. Spermine also increases the rate that viral DNA can be replicated. Some viruses (like herpes) chronically up-regulate arginase through COX-2 and other genetic signaling (Ref1 (https://www.ncbi.nlm.nih.gov/pubmed/24442486), Ref2 (https://www.ncbi.nlm.nih.gov/pubmed/31177351)).
Polyamine = (spermidine, spermine or putrescine)
"Many viruses have been shown to require polyamines (https://en.wikipedia.org/wiki/Polyamine#Natural_polyamines) for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis...Inhibition of polyamine (https://en.wikipedia.org/wiki/Polyamine#Natural_polyamines) synthesis with difluoromethylornithine (DFMO) results in a block of both HSV and HCMV replication." -Polyamines and Their Role in Virus Infection (https://mmbr.asm.org/content/81/4/e00029-17)
Taking L-arginine causes these infected cells to make more spermine from arginase activity. Since citrulline does not interact arginase, citrulline acts as an arginine-buffer pool to be converted to L-arginine on an as-needed basis. Immune cells like Natural Killer and CD8 T cells require a steady supply of arginine and NO in order to fight viral infection effectively. This citrulline buffer prevents arginine depletion.
NOS is generally anti-viral, while arginase (and spermine) is pro-viral. Now we want to block the arginase (and the production of spermine) so that the available L-arginine is only used to produce the antiviral NO. This is accomplished with an arginase inhibitor like caffeine (https://poiscenter.com/forums/index.php?topic=2695.msg31234#msg31234).
(https://i.imgur.com/ZGmYnWX.png)
I actually think tadalafil (Cialis) is a better arginase-1 inhibitor, but caffeine is widely available and cheap. So that is why I would only suggest taking citrulline malate when you are also taking an arginase inhibitor like caffeine. Even if you find a good vegetable based nitrate source (i.e. beet juice or spinach powder) to replace citrulline, I would still take an arginase inhibitor to prevent arginine depletion. My guess though is that you would have to drink a lot of beet juice to get similar NO effects as citrulline. I hope that clarifies things. :)
Update: Currently, I am not experiencing POIS symptoms except for an itchy feeling on the left side of my face and a compulsion to scratch my beard. This is true even though I have stopped taking daily supplements. For example, last week I had three orgasm within four days and still worked the full days and went to all my social engagements (but my face itched like crazy). I did a lot of experimenting with my immune system around the time when the POIS symptoms started to disappear, but it is not clear to me which one of my experiments (if any) actually made a difference. I started to notice the symptoms disappear slowly around February of this year. I am still trying to figure out why my POIS symptoms disappeared. I also don't know if this is permanent, but the improvement seems very long-term.
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Thank you in advance and it is very good to have you in the group.
Nanna 1 could you explain to me why I am having pois with pre-seminal liquid. Which battery would bless me well in this case?
infinite thanks
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That's for the highly detailed reply Nanna1. Your knowledge and research is a great asset on this board. I'm glad that your POIS symptoms have disappeared. That must be a tremendous relief. Did you ever happen to have any digestive issues that have also improved?
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I had POIS for many years. I found some moderate relief with Quantum's prepack, but it depended on how healthy I felt overall. But several years ago after an illness while traveling (not sure if it was viral, bacterial, allergens, etc) - my condition declined to a constant state of POIS or CFS or whatever it might be called.
I'm trying Nanna1's daily dose combined with some CFS treatments like d-ribose to see if it will help me get back some mobility and remove some of the constant fatigue and brain fog.
I was curious about the citrulline component. I'm taking pretty much everything except not eating vegan (tried that in the past without much success) and not taking citrulline. I have some L-Citrulline here - would that be as effective as the Citrulline Malate? In your original post I saw a lot of info but not too much on citrulline unless I missed it.
I've also noticed strenuous mental activity or physical activity gives me POIS-like symptoms. Before I would get it from physical activity but not so much from mental activity. Also I seem to be sensitive to allergens. Something like MSG gives me exactly the same effects as well.
Anyways, that's kind of rambling but curious on the citrulline malate vs l-citrulline and if there are any other things that might be good for the daily pack in my situation. It looked like a few other people in the thread had classic CFS type symptoms as well. Mine have unfortunately gotten pretty bad recently and I'm having trouble recovering this time.
Thanks.
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hapl, welcome to POISCenter!
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Has anyone found any lab tests that would indicate the presence of POIS and support this theory? Like a test that showed increased inflammation or something in a POIS state compared to normal?
I mentioned my symptoms to a doctor and they seemed open to the idea that there may be some sort of physical reaction happening but also thought it could just be a psychological issue. Also, my symptoms seem mostly psychological in nature consisting of brain fog, confusion, anxiety, unable to think clearly or focus, and fatigue. I also notice chills and after orgasm (not precum) I tend to have a sort of adrenaline rush that lasts for hours leaving me feeling exhausted but also physically stimulated and very irritable, followed by a crash later.
Such a test would be helpful for me in confirming that my symptoms are indeed caused by a physical and not just mental reaction, and would likely get the doctor (and me) on board with some of the supplements and could potentially yield further ideas.
I have looked and have seen people have posted their test results but I haven't found an example of where someone was able to get different results on a lab test depending on whether they were experiencing symptoms or not.
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dk12, welcome to the forum!
A credible POIS Test doesn’t yet exist.
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Very interesting to observe the inflammation process. Maybe I have a lot to do with pois. We would have to investigate. The vagus nerve is also implicit.
Inflamed neurons
The immune response of our body can accelerate memory loss in Alzheimer's disease.
Allison bond
age fotostock
The inflammation fulfills a possible exacerbating function of cardiovascular pathologies or tumors. It may be necessary to add another incrimination to the list: Alzheimer's disease.
According to a study published in Neurology, when an inflammation appears in the body, whether due to infection or injury, the immune response seems to accelerate memory loss in people with Alzheimer's. In that study the alterations of the cognitive faculties were examined in a period of six months; Alzheimer's patients suffering from chronic (and progressive) inflammation due to, for example, obesity or arthritis, experienced a memory loss four times greater than that of patients without such inflammation.
Those who suffered chronic inflammation, but had also experienced an acute immune response (short-lived, such as an infection) were even worse: their memory loss accelerated 10 times faster than that of patients without any medical condition.
"When we started the study, we thought that acute events would be important," explains Clive Holmes of the University of Southampton. "But we hadn't realized the weight that chronic inflammation was going to have."
Well, how is the brain injured by inflammation, either by a chronic disease or by an infection? The cause is the body's immune system, which launches an attack on invading pathogens; releases inflammatory proteins such as tumor necrosis factor, TNF. This molecule causes the vagus nerve, which extends from the brain to the abdomen and controls vital functions, such as the heartbeat, to send an electrical impulse to the brain, instructing it to release its own immune messengers.
In individuals with healthy brains, this chain of events has no greater consequence than some discomfort for a few days. But it is possible that the neurons in the brains of Alzheimer's patients are permanently in a state of attenuated inflammation. Thus, when they are exposed to the threat of a pathogen or a chronic disease, they can reach full inflammation, releasing compounds that end up being deadly to brain cells. It is not known for certain why these cells die, although Holmes suspects the annihilation of some neurons in his attempt to stop the spread of the virus, while others may die by accident in the fight to rid the body of invaders.
The results of the study could contribute to minimizing memory loss in Alzheimer's cases, suppressing chronic inflammation, for example, helping patients to lose excess weight. One could also point directly against the origin of the inflammation: "If the inflammation in the body is causing inflammation in the brain, and it is possible to dampen that signal, the blockage of the FNT would play a role in curbing Alzheimer's disease," says Holmes
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Treat brain inflammation in neurodegenerative diseases
Treat brain inflammation in neurodegenerative diseases
Inflammation of the brain plays an important role in the development of diseases such as acute brain trauma, strokes or chronic conditions such as Alzheimer's disease or sclerosis. Therefore, a possible therapeutic target for the treatment of the disease may be to block the causes of that neuroinflammation.
The work being carried out by the Mar?a Trinidad Herrero group of Program 1 of CIBERNED studies inflammation in neurodegeneration and in dementias. In this study we analyze the type of cells that overexpress CCL2 in various scenarios of T-cell infiltration in the brain, in three different species.
Lymphocyte infiltration is an important phenomenon in the inflammatory response in neurodegeneration. Brain tissue diseases such as brain tumors and viral or bacterial infections show subsets of infiltrated T cells. Therefore the control of blood cell entry may have clinical importance and therapeutic implications. Until now we knew that CCL2 is a chemokine that participates in brain inflammation, but we were not clear about its contribution to lymphocyte entry into the parenchyma.
The images obtained show that perivascular astrocytes are responsible for the expression of CCL2 in the three situations analyzed, in the three different species. The results show that the expression of CCL2 by astrocytes contributes to the entry of lymphocytes into the brain parenchyma. In the experiments carried out in mice, blocking CCL2 by a specific neutralizing antibody attenuated infiltration. On the other hand, the fact that the level of CCL2 correlates with the infiltration of T cells and not with the number of circulating lymphocytes suggests that the presence of CCL2 in astrocytes contributes to the lymphocyte extravasation process and plays an important role. at the cellular entrance.
From a therapeutic point of view, manipulation of CCL2 can have a beneficial effect on neurodegenerative diseases. The expression of CCL2 has been related to the aggressiveness of the glioma and, in fact, the use of CCL2 neutralizing antibodies has been suggested as a possible strategy for its treatment. However, CCL2 infiltration research has focused primarily on the function of tumor infiltrated macrophages, but not on other cell types. This work suggests that, like macrophages, CCL2 can also mediate lymphocyte infiltration into the glioma and contribute to the level of aggressiveness. This may be one of the therapeutic targets to control lymphocyte infiltration in brain tumors.
Consequently, in other neuroinflammatory processes, such as acute brain trauma, strokes or chronic conditions such as Alzheimer's disease or sclerosis, prolonged and sustained inflammation mediated by CCL2 may have cytotoxic effects, worsening the incidence and severity of the illness
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Hi @eliasjoelriviera, thank you for your post about effects of inflammation on the brain. What does this mean for POIS suffers, is our destiny early onset of Alzheimer?s?
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Share the article because there are many relationships. apart explains the mechanism of neuronal inflammation. It may serve to understand the mechanism of pois.
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2. Stress.
Making a brief synopsis (see Figure 1), the classical stress pathways initially involve the Hypothalamus that integrates the information from the sensory and visceral pathways, the Hypothalamus would activate two parallel routes: the SAM axis (Sympathetic-Adreno-Medullary) and the HPA axis (Hypothalamic-Pituitary-Adrenal) (Sirera et al, 2006).
Figure 1
The SAM axis begins when the sympathetic preganglionic neurons of the spinal cord receive information from the hypothalamus by activating the Sympathetic Branch and inhibiting the Parasympathetic Branch, this activation generates changes aimed at preparing the body for sustained physical exertion and decision making. The activation of sympathetic postganglionic neurons produces the release of Noradrenaline that is secreted at the level of the adrenal medulla and in brain structures: hypothalamus, limbic system, hippocampus and cerebral cortex. On the other hand, the sympathetic preganglionic neurons activate the marrow of the adrenal glands, releasing the adrenaline circulation and, to a lesser extent, norepinephrine, generating an increase in the plasma glucose and fatty acid levels, the production of thyroxine is also increased, while It produces a decrease in insulin, estrogen and testosterone levels, and inhibition of prolactin secretion.
In parallel, the HPA Axis starts from the activation of the Paraventricular Nucleus of the Hypothalamus and aims to maintain the parameters of effort and attention. The neurons of the paraventricular nucleus secrete through the portal vessels to the adenohypophysis the Corticotropin-Releasing Hormone (CRH). CRH and other related hormones enter the circulatory system that joins the hypothalamus with the anterior pituitary, and by activating the pituitary, corticotropin (ACTH) is released and to a lesser extent β-endorphin.
On the other hand, the activation of the Neurohypophysis by the magnocellular neurons of the hypothalamus generates the segregation of Vasopressin and Oxytocin that will enhance the effect of CRH. Once Corticotropin is secreted in the bloodstream, it stimulates the production and release of Glucocorticoids (cortisol and corticosterone) and mineralocorticoids by the Adrenal Glands. The effects of high levels of glucorticoids (especially cortisol) in the medium / long term on health are really harmful: increase in blood pressure, damage to muscle tissue ... so there are feedback circuits that try to maintain their levels blood within defined parameters.
Immune system activation (Hansen-Grant et al, 1998; Reiche et al, 2004) by the SAM and HPA axes occurs through two different mechanisms, on the one hand the binding of hormones to their cognitive receptors and on the other indirectly through the deregulation of the balance that has to prevail in the production of pro-inflammatory cytokines (Sirera et al, 2006b; Maes et al, 1998). Proinflammatory cytokines are soluble mediators that promote and mediate inflammatory processes, the following stand out: interleukin 1 (IL-1) is involved in the regulation of the immune process and inflammation; interleukin 6 (IL-6) which also serves as a link between the endocrine system and the immune system; and Tumor Necrosis Factor (TNF) that has the ability to destroy certain cell lines and initiates the cascade of proinflammatory cytokines and other mediators. There are data that in addition to the endocrine system, the cytokines IL-1, IL-6 and TNFα interact with the Noradrenergic, Serotonergic, and Dopaminergic systems (Kronfol & Remick, 2000
Inflammation
Inflammation is a biochemical process that can be caused by numerous endogenous or exogenous factors, in fact any immunological phenomenon capable of affecting the stability of the system can be considered as a stressor and the process may be referred to as inflammatory stress. The Immune System has the function of recognizing and destroying both external and internal pathogens. To do this, it has two intercommunicated systems: innate or nonspecific immunity and acquired or specific immunity that is usually subdivided into two complementary groups: cellular immunity and humoral immunity. It is the nonspecific system cells (neutrophils, macrophages and dendritic) that initiate the immune response through phagocytosis and inflammation. Non-specific immunity induces specific immunity, and as a result a specialized response is generated and we could say with memory. The intensity, duration and peculiar characteristics of the inflammations will depend on the affected area, the previous state and the cause that causes it.
Chronic inflammation occurs as a result of the presence of an infectious agent, antigen or for a long time due to an immune system disorder. More and more data are available that suggest that inflammation may contribute to the development of diseases such as Alzheimer's (Tan et al, 2007), cancer (Pikarsky et al, 2004), atherosclerosis (Pi?on & Kaski, 2006), and diabetes (Rosado and Mendoza, 2007), in addition to those where inflammatory processes are the same basis of the disease as Crohn or rheumatoid arthritis. Chronic inflammation is characterized by the formation of fibrous tissue and that the cell infiltrate is mainly composed of macrophages, lymphocytes and plasma cells. Among the mediators of inflammation we must highlight the role of cytokines, especially IL-1β and TNFα, capable of activating numerous humoral cascades of mediators that perpetuate the activation of the system. Cytokines (see Table 1) form an important group of proteins that act as mediators of communication between living cells. In order to understand the role of cytokines, it is necessary to understand their mechanisms of action that are both local and general, several non-exclusive ones have been postulated: passive transport to the circumventricular zone, union to the vascular endothelium and subsequent release by other agents (prostaglandins, nitric oxide) inside the brain, active transport across the blood brain barrier and peripheral activation of nerve endings where release has occurred (Watkins al, 1995
IL-1β and TNFα are present from the beginning in the sequence of activities that seek the release and use of glucose for tissue repair or elevation of body temperature, inducing the production of a second wave of cytokines, IL -1, IL-6, IL-8 and Macrophage Chemotactic Protein, derivatives of arachidonic acid or eicosanoids, platelet activating factor (PAF), free radical release and nitric oxide (NO) production, also anti-inflammatory cytokines (IL-4 and IL-10) and the release of other inflammatory mediators (Nonaka, 2001) such as bradykinins, histamine ... IL-1 and IL-6 act on the HPA axis (Chrousos, 1995) increasing ACTH and cortisol secretion. The regulatory-suppressive function of the immune response will then depend on the balance between the synthesis of different cytokines with different actions. If the inflammation is prolonged, other systems will be activated: the Endocrine, the Noradrenergic, the Serotonergic and the Dopaminergic (Kronfol & Remick, 2000).
Inflammatory stress is immunomodulator, in this sense the existence of a possible pattern of inhibition of cellular immune response (Th1) has been hypothesized while increasing humoral immunity (Th2) or vice versa (Singh et al, 1999; Agarwal & Marshall, 1998). Th1 produce (IFN-γ, TNF-β) macrophage activators, in contrast Th2 produce IL-4, IL-5, IL-10, and IL-13 activators of antibody response, other models could also exist . However, the results observed in clinical processes such as systemic Lupus erythomatous (Chang et al, 2002) or in prostate cancer (Filella et al, 2000) have been described as ambiguous. We accumulate data that suggest that proinflammatory cytokines are capable of: activating both the HPA Axis and the Locus Coeruleus - Norepinephrine system of the SAM Axis. Stimulate plasma glucocorticoid concentrations, altering the activity of hypothalamic noradrenergic neurons, reducing norepinephrine in the spleen. Glucocorticoids in turn inhibit the secretion of IL-2, IFNγ and IL-12 while increasing the secretion of IL-4 and IL-10. The chronic or intermittent inflammation that is generated by the presence of an infectious focus can thus be associated with stress, being able to initiate the cascade of biochemical processes that make it formally indistinguishable from the psychobiological process itself.
4. Depression
Depression is a syndrome or mood disorder characterized by the criterial presence of a set of symptoms: sadness, anhedonia, asthenia or lassitude, decreased attention and concentration, loss of self-confidence, pessimism, ideation of death or suicide, insomnia, anorexia? In the classic model that emerged in the 1960s, the Serotonin system and the Noradrenergic System were basically involved in the development of the syndrome (Ressler & Nemeroff, 2000; Mongeau et al, 1997; Nemeroff. 2002). However, in recent years various biochemical processes capable of generating changes in mood have been studied in depth. Among them we can highlight inflammation, ischemia, necrosis, apoptosis ... Of all of them it is probably the most studied inflammation and in which we have more data that suggest the relationship between the course of depression and that of inflammation (Licinio & Wong, 1999)
The theoretical bridge to relate inflammation and depression, as well as stress (both psychological and physical), is made up of cytokines (Connor & Leonard, 1998 and more specifically by interleukins, especially proinflammatory ones. Proinflammatory interleukins interact with Endocrine, Noradrenergic, Serotonergic and Dopaminergic Systems (Kronfol & Remick, 2000) In the most current two-way models, it is considered that both stress and depression and inflammation are capable of activating and modifying the cytokine balance and vice versa. As an example, an increase in pro-inflammatory interleukins (IL-1, IL-6, TNFα) regardless of their origin can be related to increases in norepinephrine, serotonin, dopamine, cortisol, corticotropin CRH releasing hormone, and ACTH corticotropin, together with a decrease in Gonadotropin GnRH Liberating Hormone and Natural Killer activity cells (Kronfol & Remick, 2000).
The strongest evidence of the role of cytokines in depression comes from the clinical observation of animals (Felger et al, 2007) and patients treated with interferons (Asnis & La Garza, 2005). Thus the administration of interferon-α (Gleason & Yates, 1999) (in Hepatitis C or Melanoma), of interferon-β (in Multiple Sclerosis), interferon-γ (Kaposi's Sarcoma or in Chronic Granulomatous Disease) or of interleukin -2 (in Metastatic Cancer), are associated with affective and behavioral changes that include the development of depressive episodes. Other evidence that suggests the role of the immune system in the development and consolidation of depression includes observations that depressed patients show: high levels of IL-6 (Chrousos, 1995; Maes et al, 1993); high levels of acute phase reactants and activation markers of immune cells, as well as impaired immune function (Maes et al, 1993). Cytokines appear to exert a depressive effect, directly through activation of corticotropin-releasing hormone, or indirectly causing resistance to glucorticoid receptors, which causes hyperactivity of the hypothalamic-pituitary-adrenal axis, due to inhibition of the normal feedback mechanism. . Intracranial administration of proinflammatory cytokines causes the same disease effects as their systemic administration. Therefore, proinflammatory cytokines have two places where they can exert their distinct action, in the same place of inflammation and in the CNS.
Stress, whether physical or psychological, plays an important role in triggering and evolving depressive disorders. In addition, depression has shown the existence of a biochemical profile at the endocrine and immunological level similar to that observed in stress. Glucocorticoids (Burke et al, 2005) are among the main mediators of the immunosuppressive effects generated by stressors. Among the effects described in humans we find lymphocytopenia (for example after widowing), monocytopenia, and neutropenia. Also glucocorticoids seem to be involved in reducing the production of certain cytokines (IL-1, IL-2, IL-6, IL-8, TNF) or in the increments of others such as IgA, IgE, IgG or IgM . In addition, glucocorticoids also exert their action in the brain by crossing the blood brain barrier. In this sense, mineralcorticoid receptors have been found among other locations in the pyramidal and granular neurons of the hippocampus, the olfactory nucleus, the amygdala, the striatum and the septum. Glucocorticoid receptors are present in a high proportion in the hippocampus and in the hypothalamus, we also find them in the frontal, parietal and entorhinal cortex among others. Consequently glucocorticoids can modulate various processes in the central nervous system.
In recent years, the dopaminergic system is acquiring a specific weight (Dunlop & Nemeroff, 2007) in the pathophysiology of depression. The excitatory function of Dopamine in the neurons of the Paraventricular Nucleus, where the activation of the D1 and D2 dopaminergic receptors stimulates the HPA axis and promotes corticosterone secretion, establishing a positive feedback system. And also the relationships that are being found between neurons with D2 receptors and PAR-4 proteins (Gurumurthy et al, 2005; Park et al, 2005; Mattson & Gleichmann, 2005)
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Hi All,
It was brought to my attention that I included citrulline malate in the POIS Cascade stack. It was only supposed to be listed in the Betaherpesvirinae stack. This was a mistake on my part. Citrulline (or arginine) should only be taken with an arginase inhibitor (see post (https://poiscenter.com/forums/index.php?topic=2502.msg31907#msg31907)). I apologize for this mistake.
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On a different topic: There has been a recent POIS paper which is relevant to the stacks (and model) discussed in this thread. In the paper, the researcher tested several treatments:
1. anti-histamines (centirizine and diphenhydramine)
2. alpha-blockers (https://en.wikipedia.org/wiki/Alpha_blocker) (terazosin and alfuzosin)
Anti-histamines were not effective:
"The patient was initially started on a trial of cetirizine, and instructed to orgasm weekly. After 4 weeks, the patient reported a significant improvement in abdominal cramping and reduction of diarrhea to once per week, but experienced no change in the remainder of his symptoms. Diphenhydramine had no effect on his symptoms..."
-Postorgasmic illness syndrome: potential new treatment options for a rare disorder (2019) (https://www.tandfonline.com/doi/abs/10.1080/21681805.2019.1704861?journalCode=isju20)
Alpha-blockers were effective:
"At this time, we suspected his symptoms could be in part secondary to an increased autonomic response, and he was started on a trial of terazosin, followed by several months of alfuzosin. He reported significant improvement of all symptoms on both alpha-blockers. Following ejaculation, bowel movements normalized within two days, with no cramping and only one loose stool. He denied needing prolonged sleep and reported elimination of muscle soreness. His eye dryness and redness improved significantly..."
-Postorgasmic illness syndrome: potential new treatment options for a rare disorder (2019) (https://www.tandfonline.com/doi/abs/10.1080/21681805.2019.1704861?journalCode=isju20)
These alpha-blockers (terazosin and alfuzosin) inhibit the alpha1-adrenergic receptor (a receptor for epinephrine and norepinephrine). The alpha-blocker treatment appears to be at least as effective as the COX-inhibitor treatment in Ashby and Goldmeier (2010) (https://www.ncbi.nlm.nih.gov/pubmed/20214722). In this case study, these results seem to confirm that epinephrine and norepinephrine are the chemical triggers for Post Orgasmic Illness Syndrome.
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Nanna, I tried terazosin an hour before ejaculation and it did cause a refractory ejaculation however it was POIS as usual. Does it mention regular use? Alpha blockers are also terrible with their side effects as one time I nearly fainted on one of them.
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Are there natural compounds that would have similar effects to the alpha blockers?
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Nanna, I tried terazosin an hour before ejaculation and it did cause a refractory however it was POIS as usual. Does it mention regular use? Alpha blockers are also terrible with their side effects as one time I nearly fainted on one of them.
It might be beneficial to check the pharmacokinetics for terazosin. That drug takes several days before the full therapeutic effect is reached. In the paper, they did not time the dose, so you should assume it was taken daily/regularly. They also mentioned that there were side-effects (i.e. dizziness) that made the POIS patient have to stop treatment. The key finding from the paper (https://poiscenter.com/forums/index.php?topic=2502.msg32719#msg32719) is that they verified that the alpha1-adrenergic receptor can trigger POIS. The trigger is not the same thing as the cause for the disease. It just means that the cascade of symptoms in POIS do not occur until there is a rise in adrenaline and noradrenaline (epinephrine and norepinephrine) levels. This is the same receptor that is responsible for ejaculation contractions. But these alpha-blockers do not seem to be safe treatment options for POIS.
Are there natural compounds that would have similar effects to the alpha blockers?
Hi hapl,
Adenylyl cyclase inhibitors (https://poiscenter.com/forums/index.php?topic=3151.msg31892#msg31892) might have a similar effect by inhibiting some adrenergic stimulation. But the model in the original post (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497) shows ways of hacking the adrenergic receptors.
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Nanna1, thanks a lot for your research. I could not read the Cornell study fully as I did not have access. However, it seems to be a report on a single POIS patient, not a statistical study with multiple participants.
A few folks in this forum have tried alpha blockers before - Flomax(tamsulosin), Silidosin etc. but these don't seem to have worked for POIS. Maybe I did not take these drugs right from a dosage or timing standpoint. What was the dosage and timing mentioned in the study?
I personally tried 0.4 mg of tamsulosin every day for many months. I also tried alfuzosin 10 mg for a few weeks but gave it up as I could not tolerate the side effects.
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My unsupported theory is that in my case the worst part of the POIS is somehow dopamine related.
I do not experience these physical symptoms like some other members do, or I do not notice these symptoms, everything in my case is mainly psychological and cognitive. I did have in the past some complications due some supplements, which caused me some physical symptoms, like from Magnesium or Zinc which caused me burning sensations inside which leaded to uncontrolled mini Os, but these are not my usual symptoms.
Sure I get headaches, low energy, weakness and so.. but I feel like, if I could only boost dopamine I would feel more satisfied and would not lose that feel of reward after doing things, which would I think make my POIS very tolerable. Could be wrong though.
Too bad in my country DRI supplements are really hard to find, I spoke with a doctor and so far seems only some for "nicotine addiction" dopamine inhibitors are available, I might give a try if doctor decide it is worth of trying.
But it is still in all in the air.
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these results seem to confirm that epinephrine and norepinephrine are the chemical triggers for Post Orgasmic Illness Syndrome.
I concur that epinephrine and norepinephrine seem to be tied to POIS. I realize I can get POIS symptoms without orgasm in periods of acute stress. I also realize I have a major problem dealing with stress and anxiety. I'm starting a course of Alfuzosin prescribed by my doctor. I don't believe it is the solution for me but it will be an interesting test. I also have some urinary symptoms it may help like having to urinate often and leakage after I go.
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For me personally an enzyme, called Phosphodiesterase 4 (PDE4) might be to blame for POIS symptoms as an OTC pill that's a PDE4 inhibitor (against spasms) makes me feel less moody/weird after sex. Maybe people with POIS have a defect in some or more of the PDE4 enzymes?
Just putting this out there as it could help others, too. :) It took me like 19 years to find this little and inexpensive pill that works on my POIS symptoms. I've tried all ADs, herbs, niacin, NSAIDs, you name it out there to no help.
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an OTC pill that's a PDE4 inhibitor (against spasms) makes me feel less moody/weird after sex
Interesting. What is the active compound name, and what dose do you use?
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The compound is called Drotaverine.
I discuss more of my story and that drug here: https://poiscenter.com/forums/index.php?topic=3220.0
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Hi yesyesyes,
I'm excited that you found something that works for you! Keep sharing your good news. Caffeine and caffeine metabolites (xanthine, paraxanthine, pentoxifylline, theobromine, and theophylline) are used in medical literature to produce pharmaceutical grade phosphodiesterase 4 (PDE4) inhibition.
caffeine phosphodiesterase inhibitor (https://scholar.google.com/scholar?hl=en&as_sdt=0%2C44&q=caffeine+phosphodiesterase+inhibitor&oq=caffeine+phosphodiesterase)
It is well know that PDE4 inhibitors like caffeine help stimulate an increase in beta-endorphin release.
Caffeine stimulates beta-endorphin release in blood but not in cerebrospinal fluid (1982) (https://www.ncbi.nlm.nih.gov/pubmed/6290811)
One case study hypothesized that POIS is related to a dysfunction in the mu-opioid receptor and beta-endorphin signaling.
Basically, I think that the POIS hypothesis in the following paper is correct but incomplete:
"Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen (https://www.ncbi.nlm.nih.gov/pubmed/25630453)" (Jia Yin, et al, 2015)
In that Jia Yin et. al. paper, they focus mostly on showing that IgE allergy is not involved in the POIS of one patient. However, towards the end of the paper, they suggest that POIS could be caused by low beta-endorphin signaling (low endorphins or low mu-opioid receptors).
But caffeine (and its xanthine metabolites) are non-selective phosphodiesterase inhibitors meaning that it inhibits PDE1, PDE3, PDE4 and PDE5. So it has multiple benefits for the immune system, it is all-natural and has a proven safety record (especially when taken with taurine or theanine, but not coffee). The timing and dosing information for caffeine can be found in either of these three post (Post1 (https://poiscenter.com/forums/index.php?topic=2695.msg31234#msg31234), Post2 (https://poiscenter.com/forums/index.php?topic=2502.msg21497#msg21497), Post3 (https://poiscenter.com/forums/index.php?topic=3151.msg31893#msg31893)).
It may be helpful to look at other ways to increase beta-endorphin levels naturally (laughing, meditaion, social activity with the opposite sex, etc...).
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I'm starting a course of Alfuzosin prescribed by my doctor.
Just an update on this. I took Alfuzosin for 4 days and had the side effects that are common, dizziness upon standing and fatigue. I didn't even try having an O since I thought 4 days wasn't long enough to give it a real trial. I may try again when I have an extended holiday and won't mind the side effects.
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nanna1, hi. :)
Unfortunately I'm caffeine intolerant - it makes me jittery and makes my bp too high. Even green tea does. I also have a light connective tissue disorder (often goes with MCAS). Anyone else?
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PGE2 is a mast cell mediator, see table 3: Mast Cell Biology at Molecular Level: a Comprehensive Review (https://sci-hub.se/https://link.springer.com/article/10.1007%2Fs12016-019-08769-2)
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I understand that some have had bad experiences with caffeine overdosing. In many cases, a bad experience is enough to avoid future experiences. I understand that reasoning. Please listen to your body!
But for those who are experimenting with phosphodiesterase inhibitors, caffeine has the best safety reputation and is the most effective phosphodiesterase (PDE) inhibitor available. Caffeine is also broad spectrum, meaning it inhibits multiple PDEs (PDE1, PDE3, PDE4, PDE5). It has low financial cost, high bioavailability and is readily available from healthy food sources.
I personally would not consume caffeinated beverages (or any drug based PDE inhibitor (https://poiscenter.com/forums/index.php?topic=2695.msg31234#msg31234)) on a regular basis. They are more effective at boosting endorphin levels and blocking arginase when taken as part of a complete pre-pack stack and or taken with food.
Caffeine jitters come from glutamate/dopamine imbalance. When glutamate is high and dopamine is low, too much caffeine will cause muscle shakes. The best solution is to consume caffeinated beverages with or after a meal. Food will slow the absorption and provide more dopamine production to prevent jitters. Another solution is to consume theanine and alpha-GPC with the caffeine. This has a general affect of lowering glutamate and increasing the release of dopamine.
All PDE inhibitors (including PDE4 inhibitors) change blood pressure and heart-rate at their effective dose. If you have chronic blood pressure issues, please check with your physician to see if you are healthy enough to take these drugs.
Other ways of naturally boosting endorphins includes social interaction, laughing, meditation, etc...
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nanna1, thank you for that...from this caffeine addict :)
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these results seem to confirm that epinephrine and norepinephrine are the chemical triggers for Post Orgasmic Illness Syndrome.
I concur that epinephrine and norepinephrine seem to be tied to POIS. I realize I can get POIS symptoms without orgasm in periods of acute stress. I also realize I have a major problem dealing with stress and anxiety. I'm starting a course of Alfuzosin prescribed by my doctor. I don't believe it is the solution for me but it will be an interesting test. I also have some urinary symptoms it may help like having to urinate often and leakage after I go.
Last week, and for the first time in my life, I also experienced a horrible one-week POIS period without orgasm/NE but after some stressful days. But in addition to the stress it started within a day after a restaurant visit where I ate unusual amounts of carbohydrate (French fries and some spicy sweet sauce) and particularly a dessert with lots of ice cream and a belgian wheat-waffle together with coffee. I dont use to eat that much sugar/wheat in one day since I 've been cutting down on all that. I believe that it was the stress in combination with a sugar-coffein-carbohydrate spike that released this POIS!!!
Both stress, sugars and coffein do release hight amounts of cortisol and the symptoms of extraordinary hight cortisol is inflammation, hight sebum production, muscle weaknes/pain (for me: mostly on the achilles tendon and the thigh muscle), headache, acne, hight sebum, red eyes, enlarged blood vessels, rosacea-like skin issues. I use to get it all on POIS and I got it now too, it was one of the worst POIS weeks I ever had! Totally mental paralyzed.
Now, this makes me start wondering if spikes of cortisol (or perhaps adrenaline in the absent of cortisol?) are the bad guy after all, at least one of the bad guys. Another POIS starter for me is nocturnal emissions, and very much "close-to-nocturnal-emissions" but why would hight amount of cortisol be secreted at NE's? I dont experience stress when I dream such dreams. Inflammation is certainly the main activity in POIS but are there diffrent inflammatory substances/hormones that have the same effect but are release from different triggers? I'm ever batteling with these hypothesis:
1. Hight cortisol spikes (because of mental or chemical stress) causes POIS.
2. Long time hight cortisol causes depletion of cortisol which is substituted with hight adrenaline which at spikes causes POIS.
3. Long time hight cortisol/dopamin etc causes overactive adrenals/pitutary gland that causes excess cortisol/adrenaline spikes that causes POIS.
4. Chronical low levels of oxitocin, enorphones or other feel-good hormones
Of cource everyone can have adrenaline/cortisol spikes without having POIS so there must be another factor involved and a believe that POISers have either abnormally: hight cortisol/adrenaline secretion, hight receptor response, low anabolic hormone response (testosterone, oxytocin etc) or combinations of those.
Please give your thougts about that!
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Thank you in advance and it is very good to have you in the group.
Nanna 1 could you explain to me why I am having pois with pre-seminal liquid. Which battery would bless me well in this case?
infinite thanks
Hi Eliasjoelrivera!
If the pre-seminal liquid comes in addition to an initial cause like sexual arousal, nocturnal dreams etcetera maybe it is the hormons involved with the arousal that causes the POIS rather than the liquid in itself.
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I happen to have a different version of POIS.
A- If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS and they last for 3-4 days. During this time i suffer from brain fog, excessive sleepiness, light headed, excessive sweating, irritated, cognitive impairment, fatigue, muscle weakness and headache/migraine. The more i sleep the sooner i can recover from these symptoms but they still take about 3 days at least although the symptoms become milder as i sleep more.
POIS is not triggered if i sleep at night right after sex. And due to this awkward strange reaction to sex i can not go for sex during day time. I can only have sex at night and sleep right after (in order to avoid POIS)
B- If i orgasm after masturbate, then POIS kicks in within an hour and gets worse the next day and lasts for 3-4 days. Even if i go to sleep right after masturbation/orgasm at night, it still does not help ! I get plenty of sleep yet the next day the symptoms of POIS starts to appear and gets worse the following day and then begin to subside the 3rd day and almost fully disappear by the end of 4th day from masturbation/orgasm. I did experiment few supplements but they either did not work or their effects were very short lived. I was also deficient in vitamin D3 and after taking supplements for it, the POIS symptoms got a little bit better.
In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation? And why do i have to sleep within 20min or so after sex to avoid POIS? And i don't understand why i get so heavily sleepy headed with POIS as if i am drugged and i am literally dragging myself to do daily chores not to mention the anxiety and discomfort that comes with it/pois.
Hi Luminous!
I believe that your experience has a very important piece of te POIS puzzle. The severeness of my POIS (and others here) is also dependent on such things you mention. If I would list the POIS-triggers from the worst (top) to the least it would be like this:
1. Nocturnal emission (NE) or masturbation (MB)/orgasm (O) (what time doesnt matter)
2. Hight stress + loads of sugar/coffein (new cause that I just experienced last week)
3. Near nocturnal emision (sexual arousal)
4. Orgasm from sex in morning
5. Orgasm from sex in night
So what is the difference between the top and bottom? I believe its oxytocin (and perhaps other endorphins and feel-good-hormones that are known for primarily helping one deal with stress and reduce feelings of pain)! Spikes of adrenaline/cortisol causes inflammation but oxitocin is anti-inflammatory and balances the cortisol/adrenalin immediately, on seconds! Ocytocin is released when you feel relaxed, during hugging, meditation, deep breathing, hot shower, petting a cat/dag and at normal sex with lot of skin contact. It is associated with love, but not nessecary orgasm in itself. So thats why you dont get enought of it on masturbation, or viewing porn where you produce cortisol/adrenalin, and specially too much dopamin, but not enought levels of oxitocin and/or other feel-good hormones.
It further seems that those hormones need to be secreted at the same time (probably within seconds) as orgasm (or already be in adequate amounts in the blood) to be able to stop inflammation from occuring. So they dont stop inflammaton, they stop inflammation from occuring. If you wait an hour, its too late, the damage is already done.
This also explaines why users on POIS forum has described why the POIS gett less worse if they use the following practise/products of which some are notoriously known for increasing oxytocin/endorphin levels:
Vitamin D
Vitamin C
Magnesium
Taurin
Coffee (if taken right after O, not in the long term, where it messes with hormonal balances by increases cortisol and lowering testosterone)
Lactobacillus (better gut)
Chamomile
Melatonin (higher amounts at evening/night, so sex at night causes less POIS)
Fenugreek
5HTP
GABA
L-Theanine
Green Tea
Eggs
Massage
Deep breathing immitiately after NE
Yoga
Warm and Cold showers
Normal sex (skin touching)
Sauna
Summer vacation
Exercise
Other anti-inflammatory foods and drugs could also work in the right amounts, but probably not as good as oxytocin, the bodys own super anti-inflammatory, that could be secreted in the right amounts at exactly the right time.
Of cource this doesnt try to explain why POIS happens in the first place, only the diffrent severity on diffrent triggers. Everyone doesnt experience POIS on MB, porn etc. Maybe their hormon levels are always balanced, in all weather. Their adrenals have enought of hormonal storage to manage all these diffrent form of O, 24 hours a day, 7 days a week. So by working on your hormonal systems you might be able to restore normal hormonal capacity, but that could take time and requires sexual, dietary and supplemental discipline not to mention avoidance of stress, which for many people could be very hard.
https://www.optimallivingdynamics.com/blog/25-effective-ways-to-increase-oxytocin-levels-in-the-brain
https://medium.com/@jordanfallis/25-effective-ways-to-increase-oxytocin-levels-in-the-brain-fe5ac39bc57
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Anyone who tried binaural beats, recordings of white noise and nature sounds, and Solfeggio tones? I think they really do lower cortisol and stress in general.
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Last week, and for the first time in my life, I also experienced a horrible one-week POIS period without orgasm/NE but after some stressful days. But in addition to the stress it started within a day after a restaurant visit where I ate unusual amounts of carbohydrate (French fries and some spicy sweet sauce) and particularly a dessert with lots of ice cream and a belgian wheat-waffle together with coffee. I dont use to eat that much sugar/wheat in one day since I 've been cutting down on all that. I believe that it was the stress in combination with a sugar-coffein-carbohydrate spike that released this POIS!
Mast cells being triggered by multiple triggers all at once.
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Hi Luminous,
Sorry I didn't see your questions. But they are good questions. Also thanks BoneBroth for bringing up Luminous' previous post!
...I happen to have (two) different version(s) of POIS.
A- If i don't go to sleep within 20min or so after O (following sex), then i develop typical symptoms of POIS...The more i sleep the sooner i can recover from these symptoms...
POIS is not triggered if i sleep at night right after sex....
B- If i orgasm after masturbate, then POIS kicks in within an hour ...Even if i go to sleep right after masturbation/orgasm at night, it still does not help !... I was also deficient in vitamin D3 and after taking supplements for it, the POIS symptoms got a little bit better...
In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation?...
There are two reason given in the POIS literature for a difference between POIS from sex versus masturbation. The first reason comes from the paper:
Progesterone deficiency, "Benign coital headache relieved by partner's pregnancies with implications for future treatment (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028282/)" (Selwyn Dexter, 2009)
In this paper, they conclude that the male POIS patient benefited from his wife's progesterone (exchange of sexual bodily fluids). They tested this by giving the man a progesterone mimicking drug which relieved his POIS 95 percent.
The second reason is given by the paper:
Mu-opioid receptor dysfunction, "Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen (https://www.ncbi.nlm.nih.gov/pubmed/25630453)" (Jia Yin, et al, 2015)
In this paper, they suggest that low beta-endorphin stimulation is the reason that POIS occurs. Beta-endorphin blocks some of the negative (immune suppressing) properties of norepinephrine, epinephrine and prostaglandin PGE2 (see post (https://poiscenter.com/forums/index.php?topic=3151.msg31892#msg31892)). Social interaction (especially with the opposite sex) can increase endorphin release. Laughter (comedy) is also a major endorphin releaser!
...And why do i have to sleep within 20min or so after sex to avoid POIS?...
The short answer may be that sleep boost your immune system. The sleep response is the immune system telling your body that it is not strong enough to handle POIS. The first thing that happens during sleep is that epinephrine and norepinephrine levels drop, and melatonin levels increase:
(https://i.imgur.com/FzLyQcN.png)
White circles: 24 hour sleep deprivation, Black circles: 24 hour normal sleep. Gray region (23:00 - 7:30): sleeping period
-Number and Function of Circulating Human Antigen Presenting Cells Regulated by Sleep (https://www.ncbi.nlm.nih.gov/pubmed/17520784)
(https://i.imgur.com/TWl4Eys.png)
Effects of sleep and circadian rhythm on the human immune system (https://www.ncbi.nlm.nih.gov/pubmed/20398008)
(https://media.springernature.com/original/springer-static/image/art%3A10.1186%2F1741-7015-11-79/MediaObjects/12916_2012_Article_744_Fig3_HTML.jpg)
Manipulating the sleep-wake cycle and circadian rhythms to improve clinical management of major depression (2013) (https://www.ncbi.nlm.nih.gov/pubmed/23521808)
Since the immune suppressors (epinephrine and norepinephrine) decrease and the immune enhancer (melatonin) increases, this leads to the release of immune stimulating cytokines (IL-2, IL-12, IFN-y, TNF-a, etc...). It also causes the immune suppressing cytokine IL-10 to decrease.
(http://brainimmune.com/wp-content/uploads/2011/07/T-Cell-During-Sleep-Fig2.jpg)
Figure 2 T Cell and Antigen Presenting Cell Activity During Sleep (http://www.brainimmune.com/t-cell-and-antigen-presenting-cell-activity-during-sleep/)
(http://www.brainimmune.com/wp-content/uploads/2011/07/T-Cell-During-Sleep-Fig-5.jpg)
Figure 5 T Cell and Antigen Presenting Cell Activity During Sleep (http://www.brainimmune.com/t-cell-and-antigen-presenting-cell-activity-during-sleep/)
...And i don't understand why i get so heavily sleepy headed with POIS as if i am drugged and i am literally dragging myself to do daily chores not to mention the anxiety and discomfort that comes with it/pois(?)
The immune system then produces sleep signals (adenosine, etc...) to force you to go to sleep. Once you are sleep, your immune system can increase its capabilities by using sleep to suppress norepinephrine/epinephrine levels and by releasing immune stimulating cytokines (IL-2, IL-12, IFN-y, TNF-a, etc...).
I really appreciate, the questions because they highlight the connection between POIS, sleep and immunity. On this thread, I try to focus on practical solutions for relieving POIS symptoms. And I try to avoid talking about theory in this thread. So I won't go much further other than to say that sleep (as an immune booster) is required for recovery from POIS. For a deeper discussion on theory, I recommend the threads: Transiently Induced Immune Deficiency and Therapy (https://poiscenter.com/forums/index.php?topic=3151.msg31892#msg31892) and Ideas on Herpes Induced POIS (https://poiscenter.com/forums/index.php?topic=2683.msg23764#msg23764). I hope this helps! :)
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Mediator(s): Phospholipases (including PLA2) ---> Major pathophysiologic effects: Arachidonic acid generation, inflammation
Table 1:
Differential release of mast cell mediators and the pathogenesis of inflammation (https://sci-hub.se/10.1111/j.1600-065X.2007.00519.x)
"Eicosanoids (prostaglandins, leukotrienes, and thromboxanes) are produced by catalytic conversion of arachidonic acid by the action of phospholipase A2 on membrane phospholipids. Mast cells express COX1 and COX2, which converts arachidonic acid into prostaglandins and thromboxanes with the action of specific isomerases (38). Prostaglandins increase vascular permeability and attract neutrophils. Leukotrienes are involved with smooth muscle contraction, airway constriction, and mucous secretion (39). Eicosanoids act at the local area of mast cell degranulation. "
Mast Cell: A Multi-Functional Master Cell (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701915/)
Also MCs can release mediators which upregulate COX enzymes.
This is why NSAIDs are being used in MCAD patients. A subset of POIS patients may experience release of phospholipids from MCs or mediator release which upregulates COX. These people might benefit from NSAIDs.
(https://i.imgur.com/cpuXuGZ.png)
You could replace the boxes above phospholipase A2 by a box with Mast Cell Activation or MCAD. And since ROS can be released from MCs along with other COX upregulators, you could draw a line from the MCAD box directly to ROS. An additional parallel line can be drawn from the upper MCAD box directly to PGE2 as well.
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I think patients should keep wrist BP monitor or standard BP monitor at home, this will track blood pressure continuously, here is the trusted source of BP monitor recommendation - BP Machine Price (https://top10talks.com/bp-machine-price)
Hope it will help
Thanks
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Since we are on Page 36 of this thread...
Has anyone else actually tried the daily POIS Cascade Stack from Page 1 for at least a few months and seen any improvement?
I'm not referring to the pre-pack. I'm referring to the daily regimen intended to down-regulate a1A / h1H / COX-2.
I have a call with my functional doc on Tuesday to discuss options, and at this point I'm pretty sure I'm going to just dive into the supplement plan since I'm now already taking half of the stack daily anyway.
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The methylation stack finally works for me in the past when I tried the full amounts from the stack it would cause bad brain fog and throw me off balance - bad anxiety speech problems. What did I do? I was taking lipsoomal glutathione and a binder bentonite for a month and my head felt much clearer and normal but speech problems, brain fog and autistic symptoms persisted
Then I thought I would try supporting methylation again using 200mcg - folinic acid, 75mg - sam e, 500mg-methyl b12 liposomal vitamin c 1g - and just like that I feel incredible and euphoric all brain fog and anxiety speech issues have gone I have never been able to speak this well in my life. My bad reactions to showers have stopped also.
The key is to lower sam e and folate amounts - if its not working for you empty most of the capsules and just use tiny amounts so you can see what works for you. If you react badly to methyl folate use folinic acid. I'm assume I must have had high homocysteine levels as the difference has been life changing.
I had been using liposomal vitamin c and folinic acid on their own and I was reacting terribly to the folinic acid with vitamin c, Sam e and methyl b12 were definitely needed
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Have you tried taking only SAM-E? It's the only thing in this stack that doesn't seem to make me feel sick. Other than Vitamin C.
I'm curious about Folinic Acid though.
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Drop I used to react badly to methyl folate and methyl b12 folinic acid if i took on them separately and even together the key was to lower the amounts. Sam e I haven't tried taking on its own but a full capsule I don't react well when taken with others.
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Where do get your folinic acid from?
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From Seeking health they have the best supplements as they know which forms/amounts of vitamins and minerals need to have an effect on you.
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In short, i want to understand why does my body react so differently to orgasm following sex versus masturbation?...
There are two reason given in the POIS literature for a difference between POIS from sex versus masturbation. The first reason comes from the paper:
Progesterone deficiency, "Benign coital headache relieved by partner's pregnancies with implications for future treatment (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028282/)" (Selwyn Dexter, 2009)
In this paper, they conclude that the male POIS patient benefited from his wife's progesterone (exchange of sexual bodily fluids). They tested this by giving the man a progesterone mimicking drug which relieved his POIS 95 percent.
The second reason is given by the paper:
Mu-opioid receptor dysfunction, "Postorgasmic Illness Syndrome (POIS) in a Chinese Man: No Proof for IgE‐Mediated Allergy to Semen (https://www.ncbi.nlm.nih.gov/pubmed/25630453)" (Jia Yin, et al, 2015)
In this paper, they suggest that low beta-endorphin stimulation is the reason that POIS occurs. Beta-endorphin blocks some of the negative (immune suppressing) properties of norepinephrine, epinephrine and prostaglandin PGE2 (see post (https://poiscenter.com/forums/index.php?topic=3151.msg31892#msg31892)). Social interaction (especially with the opposite sex) can increase endorphin release. Laughter (comedy) is also a major endorphin releaser!
...And why do i have to sleep within 20min or so after sex to avoid POIS?...
The short answer may be that sleep boost your immune system. The sleep response is the immune system telling your body that it is not strong enough to handle POIS. The first thing that happens during sleep is that epinephrine and norepinephrine levels drop, and melatonin levels increase:
Check this out. If you combine above theory with mast cell activation theory, all three parameters point in the same direction, coincidence?:
Melatonin: Inhibits mast cells (Increased melatonin = improved POIS symptoms)
Progesteron: Inhibits mast cells (Increased progesteron = improved POIS symptoms)
β‐Endorphin: Stimulates mast cells (Increased β‐Endorphin = worsening of POIS symptoms)
Table 1:
Neuroendocrinology of mast cells: Challenges and controversies (https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13288)
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The methylation stack finally works for me in the past when I tried the full amounts from the stack it would cause bad brain fog and throw me off balance - bad anxiety speech problems. What did I do? I was taking lipsoomal glutathione and a binder bentonite for a month and my head felt much clearer and normal but speech problems, brain fog and autistic symptoms persisted
Then I thought I would try supporting methylation again using 200mcg - folinic acid, 75mg - sam e, 500mg-methyl b12 liposomal vitamin c 1g - and just like that I feel incredible and euphoric all brain fog and anxiety speech issues have gone I have never been able to speak this well in my life. My bad reactions to showers have stopped also.
The key is to lower sam e and folate amounts - if its not working for you empty most of the capsules and just use tiny amounts so you can see what works for you. If you react badly to methyl folate use folinic acid. I'm assume I must have had high homocysteine levels as the difference has been life changing.
I had been using liposomal vitamin c and folinic acid on their own and I was reacting terribly to the folinic acid with vitamin c, Sam e and methyl b12 were definitely needed
Do you still need to continue taking liposomal glutathione or are the B vitamins and SAMe enough on their own right now?
ETA: actually Nancy Klimas, a ME/CFS researcher, recommends starting with antioxidants(just like you did) before introducing things like folate and b12. She recommends to begin with L-carnitine, glutathione, ubiquinol, vitamin C, NAC and only then proceed to folate, etc.
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Have you tried taking only SAM-E? It's the only thing in this stack that doesn't seem to make me feel sick. Other than Vitamin C.
I'm curious about Folinic Acid though.
Don't know if this applies to you, but I find that glycine(collagen) is often left out of methylation support protocols. I find that Chris Masterjohn's approach is the most sensible and I would recommend everyone to at least have a look. His other videos (unrelated to methylation) can also be very helpful sometimes.
https://chrismasterjohnphd.com/blog/2019/03/01/start-here-for-mthfr-and-methylation/
Also, another interesting article from Chris on SAMe and why it may be helpful for someone:
https://www.westonaprice.org/helps-consider-magnesium-metabolic-rate/
Basically, the reason why SAMe helps may be Mg deficiency or low metabolic rate/ATP deficiency.
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Sorry for multiple posts, but I also wanted to ask if anyone has any ideas about creatine vs SAMe? I see nanna has linked to a study that shows down regulation of a1A with SAMe, but it seems to be temporary and in rats so not sure about the significance.
For those who don't know, creatine should theoretically spare almost half of endogenous SAMe(or methyl groups in general), but creatine has been shown to have its antidepressant activity via UPregulation of a1A, so if nanna's theory is correct it should make POIS worse, but who knows.
The problem with creatine is that it affects the GI tract negatively, when its used as a monohydrate (most popular form). I wouldn't recommend this to anyone with POIS since so many people, including me, suspect that GI health is very important and we shouldn't mess with it. My experience with monohydrate was a double edge sword. It helped TREMENDOUSLY with energy, but completely messed my gut so the net effect was definitely negative.
There is creatine HCL, which seems to have no GI side effects. I have bought some, but haven't yet tested it enough to know one way or the other.
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Hi Cursed,
...I also wanted to ask if anyone has any ideas about creatine vs SAMe? I see nanna has linked to a study that shows down regulation of a1A with SAMe, but it seems to be temporary and in rats so not sure about the significance.
Neuron receptor studies involving counting numbers or percentages of receptors are not done in humans when diet is being studied. These experiments are only done in animals because, in order to count the receptors you have to kill the animal and remove the brain. The brain is then sliced into pieces and treated with chemicals to stain/tag the receptor or a related marker. This is what I do in my research. I study the brain tissue after we sacrifice and remove the brain from mice.
The regulation of receptors by SAMe is not specific to only the alpha1 adrenergic (a1A) receptor. It is a general regulator of neurotransmitter and hormone receptors through its production of phosphatidylcholine (PC) and neurotransmitter feedback loops.
"Normal membrane fluidity enhances receptor function and enhances the role of receptor coupling. To promote this function by methylating plasma phospholipids, SAMe may alter the fluidity of the neuronal membrane, affecting the function of proteins that traverse the membrane. This beneficial induction includes that of defined monoamine receptors, monoamine transporters, and other elements of the second messenger system."
-S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases Throughout Life (2018) (https://academic.oup.com/ajcn/article/76/5/1151S/4824259)
For example, SAMe increases:
- dopamine and beta-adrenergic receptors:
Age-related modification of dopaminergic and beta-adrenergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine. (https://www.ncbi.nlm.nih.gov/pubmed/6328152) - m1-acetylcholine receptors:
Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats (https://academic.oup.com/ajcn/article/76/5/1151S/4824259) - vitamin D receptors:
S-Adenosyl-L-methionine (SAMe): from the bench to the bedside molecular basis of a pleiotrophic molecule (https://academic.oup.com/ajcn/article/76/5/1151S/4824259) - Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) receptors:
Effects of the transmethylation inhibitor S-adenosyl-homocysteine and of the methyl donor S-adenosyl-methionine on rat Leydig cell function in vitro. (https://www.ncbi.nlm.nih.gov/pubmed/3029509)
For those who don't know, creatine should theoretically spare almost half of endogenous SAMe(or methyl groups in general),...
I would distinguish between methyl-group cyclers ((SAMe, folate/vitamin B9, vitamin B12) and methyl-donors (TMG, choline) in the homocysteine cycle (https://imgur.com/hq96vF1). Creatine has a very small and inefficient ability to spare methyl-donors (TMG, choline), but creatine cannot spare methyl-group cyclers (SAMe, folate/vitamin B9, vitamin B12).
SAM-e is the sole methyl donor for more than 40 methyl-group transfer enzymes (methyltransferases) (https://en.wikipedia.org/wiki/Methyltransferase) and cannot be replaced by any substance (natural or synthetic). In other words, there are many SAM-e dependent enzymes that no other methyl-donor can interact with (not even choline). It is important to note that SAM-e is not the source of methyl groups. SAM-e is cycled like folate and B12. When supplementing with SAM-e, you are not increasing the number of methyl-groups by any significant amount, you are increasing the number of parallel homocysteine cycles (https://imgur.com/hq96vF1).
(https://i.imgur.com/nvtuJyf.png)
As an analogy, consider the cylinders/pistons in a car engine. SAM-e is the cylinders and TMG is the gasoline. The car cylinders (SAM-e) are cycled and output energy (methyl-groups) each cycle. The more cylinders (SAM-e) you have, the more energy (methyl-groups) you can output per second. (By analogy, SAMe increases the horsepower). But you still need gasoline (TMG) to make the car run. ...SAM-e plays a much different role than choline or betaine. So the comparison in terms of methyl-group supplying/sparing should not be between SAM-e and creatine, it should be between TMG and creatine. And TMG (https://www.amazon.com/BulkSupplements-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B00GW6T0O8/ref=sr_1_1_sspa?ie=UTF8&qid=1506754710&sr=8-1-spons&keywords=betaine&th=1) (supplying three methyl-groups) is less expensive, being ~40% the cost per methyl-group of creatine (https://www.amazon.com/Monohydrate-Micronized-BulkSupplements-Performance-Bodybuilding/dp/B00E9M4XEE/ref=sr_1_6_s_it?s=hpc&ie=UTF8&qid=1506754724&sr=1-6&keywords=creatine&th=1) (sparing one methyl-group).
In terms of choline (methyl-group) sparing, there is no advantage to taking creatine instead TMG (or choline). However, creatine can have a very big benefit on reducing POIS symptoms as a phosphate cycler managing ATP levels.
In our car analogy, ATP would be the spark plug and creatine would be the battery. It is an imperfect analogy, but the point is that CREA and ATP supply the energy needed to recycle SAM-e and keep the homocysteine cycles (https://imgur.com/hq96vF1) going. This effect of CREA is not limited to the liver and occurs throughout the body. But it only occurs after Creatine loading (https://www.bodybuilding.com/fun/anssi1.htm).
Creatine loading is required to see an effect (beyond placebo) because of creatine's poor bioavailability and the fact that muscles absorb most of it. The best methyl donors are CDP-choline, alphaGPC, and phosphatidylcholine (PC).
methyl group math...
...DMEA, which only has two methyl groups, cannot increase choline (3 methyl groups) without receiving a methyl group from TMG (Tri-Methyl Glycine, 3 methyl groups).
(supplement name, #methyl groups, #phosphate groups)
- CDP-choline, 3, 2 (https://en.wikipedia.org/wiki/Citicoline)
- alphaGPC, 3, 1 (https://en.wikipedia.org/wiki/Alpha-GPC)
- phosphatidylcholine, 3, 1 (https://en.wikipedia.org/wiki/Phosphatidylcholine)
- TMG/betaine, 3, 0 (https://en.wikipedia.org/wiki/Trimethylglycine)
- Centrophenoxine, 2, 0 (https://en.wikipedia.org/wiki/Meclofenoxate)
- DMAE, 2, 0 (https://en.wikipedia.org/wiki/Dimethylethanolamine)
- creatine, 1, 0 (https://en.wikipedia.org/wiki/Creatine)
Both choline and tri-methyl gylcine (TMG, betaine) are converted to L-glycine when they donate their three methyl groups. Which means that choline and TMG are sources of glycine for the body. Can you share your article about creatine and a1A receptor? I am interested to read about this.
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Both choline and tri-methyl gylcine (TMG, betaine) are converted to L-glycine when they donate their three methyl groups. Which means that choline and TMG are sources of glycine for the body. Can you share your article about creatine and a1A receptor? I am interested to read about this.
Thank you for your comprehensive reply.
Here's the study I had in mind:
"The Activation of α1-adrenoceptors Is Implicated in the Antidepressant-Like Effect of Creatine in the Tail Suspension Test"
https://pubmed.ncbi.nlm.nih.gov/23357536/
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Thanks Cursed for sharing the paper! :)
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If Nanna has managed to solve his POIS at 100% which from his signature does not seem light to me since it embraces multiple clusters of symptoms, I would say that there is really hope for everyone, there is just a lack of money to finance the research and then in any case I don't know if the POIS follows the cascade he listed for each single poiser or if it changes slightly on each one.
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I noticed someone asked Nanna but I didn't see a reply. Nanna said that benfotiamine was a huge help, but I noticed it was removed from the stack. What's the reason for that?
Thanks.
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Hi hapl,
There are many supplements that can be beneficial to POIS that are not listed in the stack. I wanted the stack to reflect the bare minimum of what is required to remove symptoms. And also, I wanted the stack to be cost effective (not expensive) (see Cost effective alternatives for omega-3 (https://poiscenter.com/forums/index.php?topic=2597.msg22561#msg22561)). If something is not absolutely required, then I removed it or crossed it out from the list. But if you want to take benfotiamine and don't care about how expensive (cost-wise) it is, then it may still benefit.
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I was recently informed that there are still POIS papers discussing POIS as a semen allergy. So I wanted to comment about This. The paper (Stafie and Stafie, 2019 (https://www.researchgate.net/publication/333610277_The_Post_Orgasmic_Illness_Syndrome_POIS_Selective_Bibliography)) ruled out mastocytosis but then presented the hypothesis that POIS might be an autoimmune semen allergy. The paper of Stafie (2019) is very similar to Waldinger, et al. (2011) (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1743-6109.2010.02166.x) and Kim, et al. (2018)(Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome (https://www.smoa.jsexmed.org/article/S2050-1161(18)30019-9/fulltext)). The papers Waldinger (2011), Kim (2018) and Stafie (2019) all found elevated IgE in semen and produced positive skin prick test. But none of them was able to find an antigen associated with IgE, and they also did not have a healthy control group to compare their results to. In other words, they did not establish a cause and effect relationship between semen allergy and POIS.
Then Attia, et al. (2013) published the paper Post-orgasmic illness syndrome: a case report (version 1; peer review: 3 approved with reservations, 1 not approved) (https://f1000research.com/articles/2-113) which was reviewed by several famous POIS researchers, including 3.Goldmeier and 4.Waldinger. Abdalla Attia correctly argues that it is not possible for POIS to be caused by an allergy because the immune system would attack any part of reproductive system producing protein antigen (including sperm). Below is a direct quote from Attia's response to Waldinger's review of the paper:
"In regards to testing for allergic reactions, we would like to ask whether you think that the skin prick test is reliable as a diagnostic test for allergy. Is it valid to conclude that POIS patients are allergic to their own semen on the basis of this test and suggest that this is the cause of POIS? We would suggest that skin prick tests can lead to many false positive and negative results. As andrologists we know (and there is a body of evidence for this), that semen is regarded as foreign by the body and the immune system. Immune tolerance to semen is not present. Semen is separated from the immune system by a very competent blood-testis barrier that is formed by the highly efficient Sertoli-Sertoli cell junctional complex. We would suggest that this is not a "hypothetical membrane". In certain known pathological conditions this barrier may be broken. If this occurs, auto-antibodies can form against semen. Thus, if a subject's own semen is then injected intradermally, a reaction may take place as it is recognized as a foreign antigen. We would suggest that many people would get a positive reaction on the basis of such a prick test even though they do not suffer from POIS. If allergy to the patient's own semen is a suspected cause of POIS, it will be necessary to measure serum and seminal plasma anti-sperm antibodies; IgA, IgG and IgM, to conduct immuno bead and MAR testing and to report on the patient's seminogram changes. This might also suggest that POIS patients would be mostly infertile due to formation of anti sperm antibodies.
Given these concerns regarding prick testing, we do not believe that the cause of POIS is allergy to one's own semen and also have doubts about the use of hyposensitization as a possible treatment."
-Post-orgasmic illness syndrome: a case report (Attia, et al., 2013) (https://f1000research.com/articles/2-113) (reply to reviewer 4)
After the Attia (2013) paper, Jiang, et. al. (2015) published "Postorgasmic illness syndrome (POIS) in a Chinese man: no proof for IgE-mediated allergy to semen (https://pubmed.ncbi.nlm.nih.gov/25630453/)", which is the most important POIS paper that I know of because this is the first POIS study to use a control group. Jiang (2015) showed that healthy (non-POIS) males also have semen IgE and positive skin prick allergy test. This validated Attia's (2011) reply to Waldinger, namely that semen allergy is a common and separate disease from POIS. People need to know that you can have more that one disease, and one disease does not necessarily cause another.
After Attia, et al. (2013) and Jiang, et al. (2015), Waldinger revised his original hypothesis to exclude Type I IgE allergy from his description of POIS (Waldinger, 2016):
"POIS is not associated with increased total serum IgE concentrations." -Post orgasmic illness syndrome (MD Waldinger, 2016) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001999/)
Finally, the study "Immunophenotypical Characterization of a Brazilian POIS (Post-Orgasmic Illness Syndrome) Patient: Adding More Pieces to Puzzle (https://pubmed.ncbi.nlm.nih.gov/31612795/)" by Amicis et al. (2019) used a control group to show that men with POIS and men without POIS have similar clinical reations to dilute semen skin prick test and subcutaneous semen injections. The POIS patient did not have elevated semen IgE, but two of the non-POIS healthy controls did have elevated semen IgE. So semen allergy was shown to be a separate disease from POIS. Also, both Amicis et al. (2019) and Kim et al. (2018) showed that hypodesensitization therapy (autologous semen injections) failed to produce lasting reductions of POIS symptoms. Amicis et al. (2019) did find elevated IgG in the semen of the POIS patient. And medical test from POISers on this forum do not confirm any correlation between POIS and semen allergy:
MCAS and mastocytosis test
--8 of us show normal trypase (mast cell activation syndrome) levels (itsmel, BluesBrother (https://poiscenter.com/forums/index.php?topic=2684.msg24765#msg24765), nanna1 (https://poiscenter.com/forums/index.php?topic=2684.msg24052#msg24052), Vandemolen (https://poiscenter.com/forums/index.php?topic=2684.msg25508#msg25508), Muon, Muon's brother (https://poiscenter.com/forums/index.php?topic=2684.msg24021#msg24021), jakov (https://poiscenter.com/forums/index.php?topic=2684.msg27828#msg27828), Simon66 (https://poiscenter.com/forums/index.php?topic=2684.msg24995#msg24995)).
--11 of us show normal IgE (allergy) levels (BlueBrother (https://poiscenter.com/forums/index.php?topic=2684.msg32284#msg32284), aswinpras06, certainlypois2 (https://poiscenter.com/forums/index.php?topic=2684.msg24532#msg24532), Vandemolen, kurtosis (https://poiscenter.com/forums/index.php?topic=526.msg7660#msg7660), rjmlr (https://poiscenter.com/forums/index.php?topic=526.msg6150#msg6150), Yin POIS Study (https://www.sciencedirect.com/science/article/pii/S1743609515309632), jakov (https://poiscenter.com/forums/index.php?topic=2684.msg27828#msg27828), Depreux POIS study (https://doi.org/10.1016/j.androl.2017.06.002), kingfisher (https://poiscenter.com/forums/index.php?topic=2684.msg28087#msg28087), Arata POIS study (https://onlinelibrary.wiley.com/doi/full/10.1002/cia2.12123))
--3 of us show normal histamine levels (nanna1 tested histamine, itsmel and Muon tested histamine and N-methyl-histamine).
--1 of us show low histamine levels (Simon66 (https://poiscenter.com/forums/index.php?topic=2684.msg24995#msg24995), tested histamine and N-methyl-histamine)
--1 of us show normal PGD2 levels (muon (https://poiscenter.com/forums/index.php?topic=2684.msg24021#msg24021)).
--1 of us test negative for mastocytosis (Stafie POIS study (https://www.researchgate.net/publication/333610277_The_Post_Orgasmic_Illness_Syndrome_POIS_Selective_Bibliography/link/5e35c06d458515072d76dd5a/download))
Autoimmunity test
--5 of us have normal autoimmune panel test (nanna1 (https://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039), quotz, Vandemolen, muon, Arata POIS study (https://onlinelibrary.wiley.com/doi/full/10.1002/cia2.12123)).
--1 of us show possible autoimmunity (Iwillbeatthis), correlated with positive EBV (HHV-4) infection
--1 of us show normal/negative autoimmune antibody test for onconeural antibodies, insulin, peripheral NMDA-receptor, adrenal-cortex, potassium channel, glutamic acid decarboxylase (Muon's brother (https://poiscenter.com/forums/index.php?topic=2545.msg22020#msg22020))
Inflammation
--4 show normal C reactive protein (CRP) (kingfisher, certainlypois2 (https://poiscenter.com/forums/index.php?topic=2684.msg24532#msg24532), BluesBrother (https://poiscenter.com/forums/index.php?topic=2684.msg33828#msg33828), Simon66 (https://poiscenter.com/forums/index.php?topic=2684.msg24995#msg24995))
--3 show normal ESR (Simon66, nanna1, certainlypois2)
--1 complement system activity (C3a, C4) normal (BluesBrother (https://poiscenter.com/forums/index.php?topic=2684.msg32284#msg32284))
I think that the semen allergy hypothesis has been thoroughly studied and discredited. I suspect that men (both POISers and non-POISers) with elevated immunoglobins (IgE or IgG) in their semen have sexually transmitted diseases. Some infections like CMV and HPV can be transferred through non-sexual contact, fluid exchange or from mother to child at childbirth. This is my personal hypothesis: viruses and bacteria that enter the seminal fluid can also stimulate immune cells to produce IgE/IgG antibodies against those pathogens so that they do not infect the female or kill the sperm. Injecting those viruses or bacteria (and their IgE/IgG antibodies) back into the body is probably not a good idea. I hope this helps. :)
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Yes. What still makes me wonder if there is not something wrong with semen is that 1/ the quality of my sperm decreased importantly since I have POIS, I have now very few spermatozoa in each ejaculate ; and 2/ one of my symptoms after some time of arousal and the release of pre-cum is a pain in the testicle. But I guess that it can be explained without resorting to an allergy hypothesis.
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Hi Nana/Quantam,
what kind of autoimmune tests you guys did?
I have one more point , I have not tried SAM-e yet. I was on zoloft for three years & now off it for 3-4 months.
When I try l-tryptophan, i faced allergic reaction or more inflammation. With 5 HTP it was high heart rate & POTS kind of symptom.
My BP is normally high.
Any idea?
Finally I would like to say , when you guys supplement all these, do all of you guys have normal thyroid function.
Thyroid has helped me before.
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I tried a new brand of Sam-e one week ago and it seems like the missing link in my brain for me. I now wake up not feeling foggy, the dysautonomia I was getting through weight lifting seems to have gone when I went to the gym, and I would actually feel good after exercise also when usually I end up feeling worse in recent times, I feel more confident sociable less autistic symptoms and motivated.
I've now found out if SAM-E is helpful then one of these problems was likely the case:
· cellular methylation was dysfunction
· histamine in the brain had been elevated
· the level of pro/anti-inflammatory cytokines had been out of balance
https://epiphanyasd.blogspot.com/2015/02/autism-schizophrenia-histamine.html
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Hi Iwillbeatthis, I have a barrage of questions regarding SAM-e...
- What's your SAM-e brand and dosage?
- Are you still taking it?
- Do you take it on empty stomach?
- Do you take it before or after exercise?
- Do you also take B12, B6, and/or Folic Acid?
- Do the positive effects of SAM-e last even when you don't take it?
I have the Life Extension brand SAM-e, enteric coated, 200mg. It says on the package to take it with B12, B6, and Folic Acid. But I'm not deficient in any of these vitamins and oversupplementation of B12/Folic Acid is linked to cancer.
My post exertional malaise is pretty bad though so I'm considering experimenting with SAM-e, as it could help with some symptoms, or at least improve my liver health/jaundice and mood.
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Hi Iwillbeatthis, I have a barrage of questions regarding SAM-e...
- What's your SAM-e brand and dosage?
- Are you still taking it?
- Do you take it on empty stomach?
- Do you take it before or after exercise?
- Do you also take B12, B6, and/or Folic Acid?
- Do the positive effects of SAM-e last even when you don't take it?
I have the Life Extension brand SAM-e, enteric coated, 200mg. It says on the package to take it with B12, B6, and Folic Acid. But I'm not deficient in any of these vitamins and oversupplementation of B12/Folic Acid is linked to cancer.
My post exertional malaise is pretty bad though so I'm considering experimenting with SAM-e, as it could help with some symptoms, or at least improve my liver health/jaundice and mood.
I'm taking Piping rock sam e 200mg on a empty stomach with jarrow methylb12, methyl folate b6 lozenge( I nibble around 1/6-1/4 of it this is key as I am super sensitive to methyl vitamins - larger amounts cause bad reactions) and eithe tmg or liposomal vitamin c , I think TMG works better though. I combine these with the supplement brain gain by algonot (it isn't needed) and also vagus nerve stimulator device.
I was taking it in the morning when I woke up, the first week I did have some stomach aches the next day and also come downs, fatigue and insomnia from it but now it seems to have levelled out. Some days I will take twice and some days I will only take once.
I would take it before exercise but the gyms have closed here now
I was also feeling super stimulated (in a good way) and confident from it for the first week but now that seems to have levelled out as well I still feel benefits, and I'm way more sociable and have less autistic symptoms from taking it.
Yes I think there are long lasting benefits and before if I even nibbled a methyl b12 methyl folate lozenge or folinic acid without sam e I would feel bad for the next few days
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Question to Nanna1:
I read that your "POIS Cascade stack" should be taken daily to treat POIS/NE in a long term, but do you have any specific recommendations for what to take immidiately in the first minute/minutes after an orgasm (and the first/second day etcetera)? Is it for example important to take the "POIS Cascade stack" immidiately after the orgasm to get the least symptoms during the POIS period, or are there any other supplements or actions to take then? If so I will add it in this list of "post-packs": https://poiscenter.com/forums/index.php?topic=3578.msg37452#msg37452 (https://poiscenter.com/forums/index.php?topic=3578.msg37452#msg37452)
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I have recently tried a supplement that is purely EPA with borage oil, and I feel a hundred times better than I was feeling before. When I have tried two other DHA fish oil types I didn't feel good at all. One being a now foods high strength DHA 500, EPA 250 and the other being a low strength dha and epa one. So maybe DHA is inflammatory for me
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I have recently tried a supplement that is purely EPA with borage oil, and I feel a hundred times better than I was feeling before. When I have tried two other DHA fish oil types I didn't feel good at all. One being a now foods high strength DHA 500, EPA 250 and the other being a low strength dha and epa one. So maybe DHA is inflammatory for me
"Professor Puri, Consultant at Hammersmith Hospital and Imperial College London, is the author of over 100 scientific papers and more than 20 books He explains: “In general it has been found that as the ratio of EPA to DHA rises in the supplement used in clinical trials of certain conditions, such as depression and attention-deficit hyperactivity disorder (ADHD), the ability of the supplement to improve the condition also rises.”
We are not negating the use of DHA in all circumstances; its importance for the developing foetus, for example, cannot be over-emphasised. DHA also has properties which make it beneficial for cardiovascular and joint health. What should be recognised, however, is that these fatty acids have very distinct roles for health, particularly the role of EPA in brain function and mood disorders, for which DHA has little benefit. Studies have shown that for these conditions EPA alone is far more effective than in combination with DHA, which can inhibit the beneficial actions of EPA.
With the necessary co-factors the body can convert EPA into DHA as and when it needs it, preventing the unnecessary build-up which results from taking DHA in supplement form, thus avoiding any concerns about its high rate of oxidation"
What I use https://www.mind1st.co.uk/
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I don't think my symptoms are mast cell related I think they're because of what Nanna said : However, the release of arachidonic acid, or AA, is problematic since it is a key substrate for the production of inflammatory hormones by the enzymes 5-LOX, COX-2 and the CYP450 group [4]. It is the rapid release of AA and mass production of inflammatory hormones (such as prostaglandin E2) that triggers sickness associated with POIS.
I found a good article on Arachidonic Acid https://epiphanyasd.blogspot.com/2016/10/regulation-of-arachidonic-acid-aa.html
scroll to the bottom if you want to see the science part, Nanna you may be interested in this post. He recommends the calcium channel blocker : verapamil - has a mucosal-protective effect that occurs as a consequence of reduced mucosal leukotriene synthesis and increased prostaglandin synthesis.
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Do you still take borage oil ?
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Do you still take borage oil ?
yes I do its Epa oil with borage oil
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Pure EPA oil for ME/CFS
In the introductory chapter of this book, Professor Puri describes what he terms a breakthrough in the treatment of ME/CFS following his conclusion that a key component needed for treatment was a combination of ultra-pure EPA (completely free of any DHA) and virgin evening primrose oil. Such a product first became available in April 2004 and within 3 months he was seeing 80% of his ME/CFS patients who followed his recommendation to use this product making clinical improvements, some of which were striking.
He continues in chapters 2 and 3 by first giving an excellent background history and summary about ME/CFS, dismissing very effectively any remaining notion that it be a condition of psychological origin, and surmises that there is a great deal of evidence from a consideration of viral infections, changes in the immune system, blood fatty acid levels and brain biochemistry that persons experiencing the clinical features of M.E, as for example those involved in the Royal Free Hospital outbreak in 1955, are experiencing physical (organic) illness. He concludes that “the best explanation for the pattern of results seen in ME/CFS, with reduced NK cell activity, reduced Th 1 cell activity, increased Th 2 cell activity and increased Tc cell activity, is that there is a pre-existing long-term viral infection, to which the immune system is reacting.” page 30.
Throughout these two chapters, Professor Puri explains in straightforward terms the evidence he is using and why it is significant. He refers in some detail to studies which provide evidence of statistically significant lower values of both omega-3 and omega-6 fatty acids in red blood cells and that these would be representative of levels in brain cells. He also describes two Magnetic Resonance Spectroscopy (Neurospectroscopy) studies, which revealed statistically significant high ratios of choline/creatine and how several experts agree that this reflects a change in the turnover of fatty acids in cell membranes. All the blood, brain biochemistry and immune system findings described in Chapter 3 could be consistently brought together in one model, which provides a strong pointer to natural treatment with fatty acids.
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https://www.youtube.com/watch?v=LOdh1jCjiw8&t=623s - Video of Professor Puri at the ME research conference in 2006 explaining how EPA/fatty acids help the immune system and CFS.
80% of his ME patients made significant improvements with pure epa oil, it is key that the oil contains no DHA, I hope that some people on this forum can try out the oil and see how it effects them, its very cheap to buy.
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Interesting, I always thought DHA was a good thing. I have all the classic constant CFS symptoms in addition to POIS / MCAS / etc. I'll have to check into that. Any particular pure EPA brands you recommend?
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Interesting, I always thought DHA was a good thing. I have all the classic constant CFS symptoms in addition to POIS / MCAS / etc. I'll have to check into that. Any particular pure EPA brands you recommend?
https://www.mind1st.co.uk/why-no-dha/ - I buy mine from here and they explain why they use no DHA in the article, Puri also said that pure epa will get the body to start making its own DHA
I found the best dose for me is just one capsule before meals if I take two I don't get the same effect, however Proffessor Puri uses much higher doses in his ME patients of like 2000mg a day he also uses Vegepa instead from amazon which I have not tried but they seem similar.
Nanna's reasoning on EPA and DHA : "About Omega-3: Because of the way that EPA is metabolised in the body, it does not have any toxicity in the body. So, the more the merrier! DHA has a theoretical toxicity, but this has never been demonstrated in vivo"
I noticed healing in my brain instantly from the first capsule, my speech improved drastically also, reactions to showers became much less and no rashes anymore. I've spent thousands of pounds on different supplements and this has definitely been the best one. I must add that I've used four fish oils with DHA in the past and I end up feeling worse.
I think this oil is a must try option if you have any of these aspergers symptoms, chronic fatigue, depression, mcas, lyme disease, feeling inflamed in your brain the whole time, viral infections.
I had a bad O so POIS interrupted the healing process of the EPA for a few days but afterwards I started to feel the nice healing feeling in the brain again.
I also had a bad reaction to TDCS where autistic symptoms and speech became much worse, I assume it was because of calcium channel signalling issues, and I stopped feeling the effects of the EPA for weeks. But this has nothing to do with the EPA itself, I wouldn't recommend TDCS so much as it's really hit and miss for me - a lot of the times I end up feeling worse. Voltage gated calcium channels could be the issue.
https://epiphanyasd.blogspot.com/2016/10/regulation-of-arachidonic-acid-aa.html I want to try verapamil the calcium channel blocker mentioned in this article about Arachidonic Acid and autism. Verapamil is also a mast cell stabiliser and this article says it has fixed people's gut issues.
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I had 2 Os in the morning today for the first time in weeks and I am feeling the bad effects a lot more than I normally have been recently. I'm feeling pretty nauseous as well.
In the last few Os before this, a strange thing started happening where I would get a serotonin/endorphin boost and feel really good straight after the O, now I don't know if that was because I was taking the pure EPA or because of the Brain gain supplement but I did run out of the brain gain supplement for a few weeks now as I wasn't sure whether I should continue it. Today I didn't get that "feel good" boost after O at all. And in the times before this I was mainly getting the symptoms the day after the O however I was only doing one O and usually in the evening.
Anyway I'm going to order the flavonoid/folinic acid brain gain supplement again to see if it was that, I'm also going to buy cystoprotek as I want my bladder to heal.
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Interesting, I always thought DHA was a good thing. I have all the classic constant CFS symptoms in addition to POIS / MCAS / etc. I'll have to check into that. Any particular pure EPA brands you recommend?
This is the brand Professor Puri recommends https://www.amazon.com/gp/product/B01J1O8WBE (https://www.amazon.com/gp/product/B01J1O8WBE)
I have not tried it. I am just answering your question.
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Hello guys, I read the first page and it's seem very interesting so thanks you for that!
Can you tell me if we got possitve feeback about this and what are the news after 4 years? If I want to try can you tell me what should I buy and how should I do it? Sorry but I'm reading so many different think about pois and I'm a little bit confused and lost right now but this stuff seems very promising.
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After over a decade, I believe I have cured my POIS. I wanted to open source my supplement stack to get feedback/improvemnets and to help others going through what I went through.
During orgasm there is a transient increase in norepinephrine release [1] (see Neuroendocrine responses to arousal and orgasm (https://poiscenter.com/forums/index.php?topic=2900.msg26917#msg26917)).
(https://i.imgur.com/43RWkMg.png)
Postorgasmic illness syndrome (POIS) occurs when there is an overexpression of the ?1-adrenergic (a1A) receptor and a subsequent over-stimulation of a1A by rising norepinephrine levels [2]. Part of the effect of ?1-adrenergic , a1A, stimulation is to obtain methyl groups (choline) from the phospholipid bilayer (http://aocs.files.cms-plus.com/LipidsLibrary/images/ImportedImages/lipidlibrary/animbio/phospholipases/Figure04.png) stored in the form of phosphatidylcholine (PC) [3]. a1A stimulation upregulates the enzymes Phospholipase A2 and C, which remove a PC-arachidonic acid molecule from the cell wall (lipid bilayer) and separates PC from arachidonic acid (omega-6 fatty acid, AA) [4]. PC is now free to produce choline and replenish the pool of methyl groups consumed in both semen and neurotransmitter production.
However, the release of arachidonic acid, or AA (https://en.wikipedia.org/wiki/Arachidonic_acid#The_synthesis_and_cascade_in_humans), is problematic since it is a key substrate for the production of inflammatory hormones by the enzymes 5-LOX, COX-2 and the CYP450 group [4]. It is the rapid release of AA and mass production of inflammatory hormones (such as prostaglandin E2) that triggers sickness associated with POIS.
During normal sexual activity, histamine is not elevated (Becker et. al. 2011 (https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0272.2011.01222.x)). However, POIS-like symptoms could be stimulated by non-coital external allergens (food, pollution, etc...), by replacing norepinephrine with either histamine or glutamate, and replacing a1A receptor with either the h1-histaminergic (h1H) or NMDA (NR2B) receptor. For example, histamine stimulation of h1H upregulates the enzyme Phospholipase A2, leading to the same release of PC and AA as discussed above [5, 6].
(https://i.imgur.com/cpuXuGZ.png)
Blocking both of the processes represented by red arrows in the figure above would, according to this theory, stop POIS. In other words, each red path is a required step for the disease to manifest. And the upregulation of NF-kB (NF-kappa Beta) by reactive oxygen species (ROS) is a required step for the increased production of COX-2 and inflammation (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769).
We can refer to the cascade of events, starting with simulation of the a1A, h1H, NR2B receptors and ending with the production of inflammatory prostaglandins, as the POIS Cascade. To stop POIS, you have to modify the POIS Cascade by inhibiting three key events:
1. ?1-adrenergic and h1-histamine receptor overexpression
2. NF-kB upregulation and inflammatory cytokine (https://en.wikipedia.org/wiki/Cytokine) production
3. arachidonic acid production and release from the PC-arachidonic acid complex
(1) a1A receptor expression is down regulated by the universal methyl group donor S-adenosyl-methionine (SAM-e) by donating its methyl group through methyltransferase enzymes [7]. In this way, SAM-e prevents the breakdown of the phospholipid bilayer [8] and the subsequent metabolism of AA [9]. h1H receptor expression is down regulated by Protein Kinase C (PKC) inhibition [10]. PKC is potently inhibited by thiamine diphosphate, the active form of vitamin B1 [11]. Moreover, thiamine supplementation reduces median histamine levels [12].
(2) Vitamin D3 is a strong inhibitor of NF-kB and COX-2 production [Ref link (http://www.jbc.org/content/289/17/11681.long)]. D3 accomplishes this by inhibiting the production of inflammatory cytokines such as TNF-a, IL-1B, IL-6, etc... [schematic diagram (https://i.imgur.com/xXCit9H.jpg)]
(3) In the absence of dietary AA, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce AA incorporation into the phospholipid bilayer and decrease the production of inflammatory prostaglandins such as PGE2 [4, 13]. Moreover, EPA directly competes with AA for access to enzymes 5-LOX and COX-2 [4]. And unlike AA, the metabolic products of EPA interaction with these enzymes are anti-inflammatory (link (https://en.wikipedia.org/wiki/Resolvin)).
For a literature review of POIS related research see POIS literature review (https://poiscenter.com/forums/index.php?topic=2683.msg23777#msg23777):
-----------------------------------------
Below I provide two separate supplement stacks that have given me complete relief of POIS symptoms. "The Betaherpesvirinae stack" is a prepack that targets a specific reactivation mechanism of cytomegalovirus (CMV, HHV-5) and herpes virus 6 (HHV-6) involving suppression of NF-kB and COX activity (see RefSE1 (https://www.ncbi.nlm.nih.gov/pubmed/8943952), RefSE2 (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). More details on how herpes viruses may initiate POIS can be found here (link (http://poiscenter.com/forums/index.php?topic=2683.msg23764#msg23764)). "The POIS Cascade stack" is the general daily health supplement (and vegan diet) regime that I use to treat my POIS, NE, and reduce exercise induced DOMS. These are two separate stacks which are not meant to be taken together. The below quantities for each stack are listed per dose.
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (https://www.amazon.com/Jarrow-Formulas-Promotes-Strength-Enteric-Coated/dp/B0013OVW0O/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1504971308&sr=1-4&keywords=sam-e%2B200mg&th=1) (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---Pyridoxal-5-phosphate, P-5-P vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Metafolin or folinic acid, vitamin B9 (less than 200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (>50mcg, sublingual) [methyl group cycler] (https://www.amazon.com/Jarrow-Formulas-Pyridoxal-5-phosphate-Lozenges-Supports/dp/B01IJR5VM2/ref=sr_1_26?keywords=Metafolin&qid=1559879958&s=gateway&sr=8-26)
nannan1, thank you for your post, I want to ask what kind of Vitamin B12 should I take, you said cyanocobalamin should be taken, but the url you shows that it is methylcobalamin. and could you help me to know, the vitamin B9 you recommended is the same as the methylfolate@now as this https://www.amazon.com/NOW-Supplements-Metabolically-Co-Enzyme-Vitamin/dp/B01G5EQEWC/ref=sr_1_1?crid=7E5APE1IM2BI&keywords=methyl+folate&qid=1646050696&sprefix=methylfolate%2Caps%2C395&sr=8-1 . thank you!
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Would it be possible or helpful to combine this stack with the transient immune suppression stack? And if we're not trying to minimize cost, does adding extra 5-LOX like boswellia or COX-2 inhibiting herbs potentially add to the efficacy?
I've found some of this helpful for CFS-like symptoms in general, but I haven't yet found the right 'combo'. Taking copper before meals gives me some nausea, so I assume that means it's doing something. Taking Alpha GPC, SAMe, Methyl B, etc seems to improve my headaches, brain fog, etc - but maybe I need to raise the dosage. Right now taking 300mg Alpha GPC x 2, 500mg TMG x 1, 200mg SAMe x 2, a couple lecithin capsules, one Jarrow Methyl B (split in half, so taken twice a day). And some 150mg benfotiamine, etc.
Anyways, mainly curious thoughts (especially nanna1 if he checks in) on combining this stack with the Transient Immune stack.
Thanks.
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If this could explain parts of the POIS-trigger, I still would have a few questions:
- Where is the vascular/balloon injury located?
- What caused the original injury?
- Why does the injury not heal now?
In terms of question 1, POIS symptoms are top-bottom asymmetric in everyone but also left-right asymmetric in some. So the inability to heal properly would have to be localized to specific vessels in the body, while not affecting healing in other blood vessel locations. I suspect that the answers to questions 2 and 3 are the same. Whatever would cause the original injury is also probably keeping it from healing, unless the original injury was a random event.
If you have any corrections or other thoughts, please share. That was interesting!
Piezo and CGRP? https://www.mdpi.com/1422-0067/21/3/696/htm
(https://www.mdpi.com/ijms/ijms-21-00696/article_deploy/html/images/ijms-21-00696-g002.png)
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Dear nanna1,
thank you for sharing this cascade model to explain POIS with the overexpression or overstimulation of the a1A receptor. This post actually helped me the most and I am struck by the captivating clarity of model and conclusions.
You mention in one of the responses that Benfotiamime was one of the first things you started with which got you on the right track and I guess that the same is true for me among other important components. I was actually triggered by your post! Now I see that Benfotiamine was recently crossed out in your original post and you explained this with the relatively high costs in one of your later responses. Since the motivation to take it out in the stack is not mentioned in your original post as far as I can see, and there is a strong relevance for the a1A receptor, I would like to ask you to include it again in your stack and instead make clear that one could consider skipping it if the budget is limited. I am writing this since I am convinced about its relevance for me. It can also be possible that - since benfotiamine is fat soluble - a regular continuous intake of such a high dosis is not required to have an effect and maybe one could reduce the dosis after a while.
Another comment I would like to make is that I am thinking of a connection of POIS with the COMT polymorphism which can be a potential genetic explanation for an overstimulation of the a1A receptor. This would also explain why the intellectual level of posts in this forum is far above average. The COMT polymorphism is associated with high senitivity and intellectual giftedness. ;-)
All the best!
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Where is nanna1 folks, I truly miss nanna1's presence here, he has contributed a wealth of knowledge here (and to me).
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Where is nanna1 folks, I truly miss nanna1's presence here, he has contributed a wealth of knowledge here (and to me).
Have you tried Private Messaging him?
https://poiscenter.com/forums/index.php?action=pm;sa=send
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Where is nanna1 folks, I truly miss nanna1's presence here, he has contributed a wealth of knowledge here (and to me).
Have you tried to PM (Private Message) him?
https://poiscenter.com/forums/index.php?action=pm;sa=send
swell, I also sent (via PM) nanna1 a copy of our chat (above).
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Thanks Demo, I did not message nanna1, but I just am immensely intrigued from this great person (and that is why I love this forum a lot too, it changed my life few yrs back). There are aspects of nanna's theory I don't agree with (and as a matter of fact, I barely agree with anyone, including myself often), however this person has done such a seminal/stunning work on this topic, and his Q&A's has been so darn cool, to engage with this person is a "privilege".
I hope nanna is doing well (and all of you folks too). POIS affected my life so so much, but sadly about time when I conquered it, I got setback after setback - pandemic started and my family has been left devastated. I lost the most and only precious thing in my life - mother, and oddly for myself, I don't even know of getting infected so far. So conquering or taming pois has today zero meaning for me, life seems so surreal, so redundant/extra/useless.
swell, I also sent (via PM) nanna1 a copy of our chat (above).
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Thanks Demo, I did not message nanna1, but I just am immensely intrigued from this great person (and that is why I love this forum a lot too, it changed my life few yrs back). There are aspects of nanna's theory I don't agree with (and as a matter of fact, I barely agree with anyone, including myself often), however this person has done such a seminal/stunning work on this topic, and his Q&A's has been so darn cool, to engage with this person is a "privilege".
I hope nanna is doing well (and all of you folks too). POIS affected my life so so much, but sadly about time when I conquered it, I got setback after setback - pandemic started and my family has been left devastated. I lost the most and only precious thing in my life - mother, and oddly for myself, I don't even know of getting infected so far. So conquering or taming pois has today zero meaning for me, life seems so surreal, so redundant/extra/useless.
swell, I also sent (via PM) nanna1 a copy of our chat (above).
swell, i’m very sorry to hear of your setbacks!
Best wishes,
Demo
cc: swell/Private Message
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Thanks Demo.
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i am currently on pois cascade stack ,5 days till now ,i hope it works for me
i want to know what do think of flibanserin drug ? there is a research here on poiscenter carried by scientists
thanks
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Nanna1s theories & corresponding supplement stacks have really been ground-breaking for my POIS and path moving forward. His POIS Cascade Stack worked amazingly for around a month, especially in regards to fixing my food sensitivities, but since then the effectiveness has slowly dwindled. I have a few ideas in regard to why the method has become less effective, which is what I am attempting to fix/focus on currently. My main hypothesis is that I began eating foods higher in Omega-6, off the back of months of a high Omega-3 and low Omega-6 diet (animal-based).
I created a video on this talking about my experience if anyone's interested: https://www.youtube.com/watch?v=kE27bYZ9uF0
Just for context, my animal-based method is still very effective. It's just extremely restrictive food-wise, which is why I am exploring other methods around here (and of course cures). My big picture goal is still to cure this darn thing, which Nanna1s theories have given me more confidence then ever...
So to that I really do say, Nanna1s theories have been an enormous breakthrough for me. The guy sounds like a genius.
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I recently gotten tested for viruses. These are the results:
Tested negative for HHV-1, HHV-2, EBV (HHV-4), CMV (HHV-5). Tested positive for VZV (HHV-3) and HHV-6.
I also want to mention Monolaurin. While Nanna1's stack was no longer working, I attempted his Immune Competence Therapy and was recommended Monolaurin and Propolis to take alongside it by my functional medicine specialist. Turns out Monolaurin was extremely effective for combating POIS symptoms including my food sensitivities. It was remarkable in the time that I used it and would completely recommend others to experiment with it (if you can't get Nanna1s POIS Cascade Stack working.) It is known to be a potent anti-viral, anti-microbial, anti-bacterial for a variety of pathogens/viruses. It is also relatively safe. It worked very well even when taken after symptoms presented. It is not as effective as the POIS Cascade Stack, but certainly 90-95% potent at reducing symptoms.
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Once again, tanks Warrior for these incredible informations and these new additions to Nanna1's theory :) Makes me want to get tested for the herpes virus.
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Just read that human Semen contains LARGE amounts of prostaglandins. These compounds have a huge role in inflammation. I think we are either reacting to them after O, or their replenishment. The diagram below shows a hypothesis from nanna1, not sure if he realizes that semen is loaded with Prostaglandins already. I assume so, but not certain.
A search of this forum shows that Niacin has an effect on Prostaglandins. I think we are on to something here guys! Prostaglandins also play a role in ME/CFS, and MCA. Go to Healthrising.com and do a search on the prostaglandins and you will see lots of hits.
Here is a link that states that Prostaglandins are abundant in semen:
https://www.nature.com/articles/s41598-023-31603-x
Do a search you will find lots more.
After over a decade, I believe I have cured my POIS. I wanted to open source my supplement stack to get feedback/improvemnets and to help others going through what I went through.
During orgasm there is a transient increase in norepinephrine release [1] (see Neuroendocrine responses to arousal and orgasm (https://poiscenter.com/forums/index.php?topic=2900.msg26917#msg26917)).
(https://i.imgur.com/43RWkMg.png)
Postorgasmic illness syndrome (POIS) occurs when there is an overexpression of the ?1-adrenergic (a1A) receptor and a subsequent over-stimulation of a1A by rising norepinephrine levels [2]. Part of the effect of ?1-adrenergic , a1A, stimulation is to obtain methyl groups (choline) from the phospholipid bilayer (http://aocs.files.cms-plus.com/LipidsLibrary/images/ImportedImages/lipidlibrary/animbio/phospholipases/Figure04.png) stored in the form of phosphatidylcholine (PC) [3]. a1A stimulation upregulates the enzymes Phospholipase A2 and C, which remove a PC-arachidonic acid molecule from the cell wall (lipid bilayer) and separates PC from arachidonic acid (omega-6 fatty acid, AA) [4]. PC is now free to produce choline and replenish the pool of methyl groups consumed in both semen and neurotransmitter production.
However, the release of arachidonic acid, or AA (https://en.wikipedia.org/wiki/Arachidonic_acid#The_synthesis_and_cascade_in_humans), is problematic since it is a key substrate for the production of inflammatory hormones by the enzymes 5-LOX, COX-2 and the CYP450 group [4]. It is the rapid release of AA and mass production of inflammatory hormones (such as prostaglandin E2) that triggers sickness associated with POIS.
During normal sexual activity, histamine is not elevated (Becker et. al. 2011 (https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0272.2011.01222.x)). However, POIS-like symptoms could be stimulated by non-coital external allergens (food, pollution, etc...), by replacing norepinephrine with either histamine or glutamate, and replacing a1A receptor with either the h1-histaminergic (h1H) or NMDA (NR2B) receptor. For example, histamine stimulation of h1H upregulates the enzyme Phospholipase A2, leading to the same release of PC and AA as discussed above [5, 6].
(https://i.imgur.com/cpuXuGZ.png)
Blocking both of the processes represented by red arrows in the figure above would, according to this theory, stop POIS. In other words, each red path is a required step for the disease to manifest. And the upregulation of NF-kB (NF-kappa Beta) by reactive oxygen species (ROS) is a required step for the increased production of COX-2 and inflammation (http://poiscenter.com/forums/index.php?topic=2683.msg23769#msg23769).
We can refer to the cascade of events, starting with simulation of the a1A, h1H, NR2B receptors and ending with the production of inflammatory prostaglandins, as the POIS Cascade. To stop POIS, you have to modify the POIS Cascade by inhibiting three key events:
1. ?1-adrenergic and h1-histamine receptor overexpression
2. NF-kB upregulation and inflammatory cytokine (https://en.wikipedia.org/wiki/Cytokine) production
3. arachidonic acid production and release from the PC-arachidonic acid complex
(1) a1A receptor expression is down regulated by the universal methyl group donor S-adenosyl-methionine (SAM-e) by donating its methyl group through methyltransferase enzymes [7]. In this way, SAM-e prevents the breakdown of the phospholipid bilayer [8] and the subsequent metabolism of AA [9]. h1H receptor expression is down regulated by Protein Kinase C (PKC) inhibition [10]. PKC is potently inhibited by thiamine diphosphate, the active form of vitamin B1 [11]. Moreover, thiamine supplementation reduces median histamine levels [12].
(2) Vitamin D3 is a strong inhibitor of NF-kB and COX-2 production [Ref link (http://www.jbc.org/content/289/17/11681.long)]. D3 accomplishes this by inhibiting the production of inflammatory cytokines such as TNF-a, IL-1B, IL-6, etc... [schematic diagram (https://i.imgur.com/xXCit9H.jpg)]
(3) In the absence of dietary AA, omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce AA incorporation into the phospholipid bilayer and decrease the production of inflammatory prostaglandins such as PGE2 [4, 13]. Moreover, EPA directly competes with AA for access to enzymes 5-LOX and COX-2 [4]. And unlike AA, the metabolic products of EPA interaction with these enzymes are anti-inflammatory (link (https://en.wikipedia.org/wiki/Resolvin)).
For a literature review of POIS related research see POIS literature review (https://poiscenter.com/forums/index.php?topic=2683.msg23777#msg23777):
-----------------------------------------
Below I provide two separate supplement stacks that have given me complete relief of POIS symptoms. "The Betaherpesvirinae stack" is a prepack that targets a specific reactivation mechanism of cytomegalovirus (CMV, HHV-5) and herpes virus 6 (HHV-6) involving suppression of NF-kB and COX activity (see RefSE1 (https://www.ncbi.nlm.nih.gov/pubmed/8943952), RefSE2 (https://www.ncbi.nlm.nih.gov/pubmed/9686761)). More details on how herpes viruses may initiate POIS can be found here (link (http://poiscenter.com/forums/index.php?topic=2683.msg23764#msg23764)). "The POIS Cascade stack" is the general daily health supplement (and vegan diet) regime that I use to treat my POIS, NE, and reduce exercise induced DOMS. These are two separate stacks which are not meant to be taken together. The below quantities for each stack are listed per dose.
The POIS Cascade stack:
On an empty stomach with water or juice, twice daily (water soluble):
---SAM-e (https://www.amazon.com/Jarrow-Formulas-Promotes-Strength-Enteric-Coated/dp/B0013OVW0O/ref=sr_1_4_s_it?s=hpc&ie=UTF8&qid=1504971308&sr=1-4&keywords=sam-e%2B200mg&th=1) (enteric coated)(200mg) [terminal methyl donor, a1A downregulator]
---Pyridoxal-5-phosphate, P-5-P vitamin B6 (2mg - 25mg) [homocysteine regulator]
---Metafolin or folinic acid, vitamin B9 (less than 200mcg) [methyl group cycler]
---cyanocobalamin, vitamin B12 (>50mcg, sublingual) [methyl group cycler] (https://www.amazon.com/Jarrow-Formulas-Pyridoxal-5-phosphate-Lozenges-Supports/dp/B01IJR5VM2/ref=sr_1_26?keywords=Metafolin&qid=1559879958&s=gateway&sr=8-26)
nannan1, thank you for your post, I want to ask what kind of Vitamin B12 should I take, you said cyanocobalamin should be taken, but the url you shows that it is methylcobalamin. and could you help me to know, the vitamin B9 you recommended is the same as the methylfolate@now as this https://www.amazon.com/NOW-Supplements-Metabolically-Co-Enzyme-Vitamin/dp/B01G5EQEWC/ref=sr_1_1?crid=7E5APE1IM2BI&keywords=methyl+folate&qid=1646050696&sprefix=methylfolate%2Caps%2C395&sr=8-1 . thank you!
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https://youtu.be/R0AB5Alx0pE?si=fKOe8RlFEhFZVhT9
I don’t have a scientific background, but from much of the info I’ve been researching in this topic, it’s still very effective to supplement high Omega-3 to reduce AA in the inflammatory cascade, even while following a diet high in AA. At least that’s what it seems.
High doses of Omega-3 are probably required to inhibit AA. Would be interesting to experiment with.
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I believe that for me pois is caused by inflammation too.
I have some shoulder and elbow issues that have always been on and off from over 10 years ago, seemingly randomly appearing out of nowhere and also disappearing. Only a year or two ago I came to understand that it happens when I am not feeling well in general (a pois episode for example) and have high inflammation in my body in general.
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Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
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Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
If I remember correctly:
The POIS Cascade Stack and the Betaherpesvirinae Stack are not intended to be taken together.
The POIS Cascacde Stack works to inhibit POIS inflammatory pathways via D3/methylation/zero AA, requiring a vegan diet (zero arachidonic acid [AA] consumption) and/or high Omega-3 to replace AA, but apparently only effective with vegan diet (zero AA). The Betaherpesvirinae stack works to inhibit those same inflammatory pathways (which he hypothesised the Herpes virus as a possible cause for POIS) but was created for those who can't go on a vegan diet (a diet devoid of AA which triggers one of the POIS inflammatory pathways according to him). He hypothesised you can stop AA inflammatory pathway (temporarily) through Betaherpesvirinae stack, even if consuming AA.
The Betaherpesvirinae stack has more pharmaceuticals so I would be more cautious taking long-term and make sure you take his drug detox recommendations along with it.
You could try both and just see what works. His intention with these stacks was to improve/fix POIS symptoms, not cure. His immune competence therapy (broad-spectrum pathogen load reduction) (https://poiscenter.com/forums/index.php?topic=3151.msg31889#msg31893) was intended as a potential cure.
-
Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
If I remember correctly:
The POIS Cascade Stack and the Betaherpesvirinae Stack are not intended to be taken together.
The POIS Cascacde Stack works to inhibit POIS inflammatory pathways via D3/methylation/zero AA, requiring a vegan diet (zero arachidonic acid [AA] consumption) and/or high Omega-3 to replace AA, but apparently only effective with vegan diet (zero AA). The Betaherpesvirinae stack works to inhibit those same inflammatory pathways (which he hypothesised the Herpes virus as a possible cause for POIS) but was created for those who can't go on a vegan diet (a diet devoid of AA which triggers one of the POIS inflammatory pathways according to him). He hypothesised you can stop AA inflammatory pathway (temporarily) through Betaherpesvirinae stack, even if consuming AA.
The Betaherpesvirinae stack has more pharmaceuticals so I would be more cautious taking long-term and make sure you take his drug detox recommendations along with it.
You could try both and just see what works. His intention with these stacks was to improve/fix POIS symptoms, not cure. His immune competence therapy (broad-spectrum pathogen load reduction) (https://poiscenter.com/forums/index.php?topic=3151.msg31889#msg31893) was intended as a potential cure.
Thanks Warrior.
I will begin Cascade Stack and take Betaherpesvirinae Stack before orgasm for now, as Cascade Stack is meant to be taken for a month before being efficient. I'll update.
-
Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
If I remember correctly:
The POIS Cascade Stack and the Betaherpesvirinae Stack are not intended to be taken together.
The POIS Cascacde Stack works to inhibit POIS inflammatory pathways via D3/methylation/zero AA, requiring a vegan diet (zero arachidonic acid [AA] consumption) and/or high Omega-3 to replace AA, but apparently only effective with vegan diet (zero AA). The Betaherpesvirinae stack works to inhibit those same inflammatory pathways (which he hypothesised the Herpes virus as a possible cause for POIS) but was created for those who can't go on a vegan diet (a diet devoid of AA which triggers one of the POIS inflammatory pathways according to him). He hypothesised you can stop AA inflammatory pathway (temporarily) through Betaherpesvirinae stack, even if consuming AA.
The Betaherpesvirinae stack has more pharmaceuticals so I would be more cautious taking long-term and make sure you take his drug detox recommendations along with it.
You could try both and just see what works. His intention with these stacks was to improve/fix POIS symptoms, not cure. His immune competence therapy (broad-spectrum pathogen load reduction) (https://poiscenter.com/forums/index.php?topic=3151.msg31889#msg31893) was intended as a potential cure.
Also, after the Cascade stack stopped being effective for you, could you fix it again ? Could you verify your theory on Omega 6 ?
-
Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
If I remember correctly:
The POIS Cascade Stack and the Betaherpesvirinae Stack are not intended to be taken together.
The POIS Cascacde Stack works to inhibit POIS inflammatory pathways via D3/methylation/zero AA, requiring a vegan diet (zero arachidonic acid [AA] consumption) and/or high Omega-3 to replace AA, but apparently only effective with vegan diet (zero AA). The Betaherpesvirinae stack works to inhibit those same inflammatory pathways (which he hypothesised the Herpes virus as a possible cause for POIS) but was created for those who can't go on a vegan diet (a diet devoid of AA which triggers one of the POIS inflammatory pathways according to him). He hypothesised you can stop AA inflammatory pathway (temporarily) through Betaherpesvirinae stack, even if consuming AA.
The Betaherpesvirinae stack has more pharmaceuticals so I would be more cautious taking long-term and make sure you take his drug detox recommendations along with it.
You could try both and just see what works. His intention with these stacks was to improve/fix POIS symptoms, not cure. His immune competence therapy (broad-spectrum pathogen load reduction) (https://poiscenter.com/forums/index.php?topic=3151.msg31889#msg31893) was intended as a potential cure.
Also, after the Cascade stack stopped being effective for you, could you fix it again ? Could you verify your theory on Omega 6 ?
Yes that's correct to some degree. When I first begun taking SAMe, it felt like a miracle. It was like an off switch for my entire condition, including my food sensitivities. This lasted around 3-4 weeks until symptoms began emerging again. For whatever reason, it stopped working at 100%. I tried lots of different methylation nutrients, supporting minerals, buffer nutrients like folate etc but nothing worked 100% long-term. But I do think it did "permanently" top up my methylation such that I no longer need to constantly take B vitamins, eggs (choline), etc. Before SAMe, I always felt an enormous difference before and after re my B complex, eggs, etc. Like I needed to take the B complex daily to feel good. These days I don't really feel the need as much for methylatio nutrients, apart from eggs and red meat for POIS.
For what it's worth tho, my sensitivties and POIS definitely seemed to permanently improve since the SAMe, but it's hard to put a number on exactly how much.
I also don't know about SAMe's long-term safety so I am personally hesitant to continue taking it long-term as well, even tho I do think it benefited me.
Nanna1's stack also taught me how important D3 serum is. D3 serum is king.
Re the Omega-6, I honestly have no idea. It's too difficult to test. These days I stick to a low seed oil diet given that I eat so much saturated and animal fat. Vegetable oils oxidise cholesterol apparently. The science is a bit controversial, but I definitely don't want to eat both concurrently. I'm also seeing a low-carb Dr here in Aus who advises to keep Omega-6/seed oils virtually to zero. I also personally haven't responded at all to Omega-3, hasn't made any impact on my POIS whatsoever but for others it's been a gamechanger.
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Does someone know if both Nanna?s stack can be combined ?
Meaning taking the cascade stack for long term and the other one as a pre pack.
Also, there are very few testimonies on his prepack.
If I remember correctly:
The POIS Cascade Stack and the Betaherpesvirinae Stack are not intended to be taken together.
The POIS Cascacde Stack works to inhibit POIS inflammatory pathways via D3/methylation/zero AA, requiring a vegan diet (zero arachidonic acid [AA] consumption) and/or high Omega-3 to replace AA, but apparently only effective with vegan diet (zero AA). The Betaherpesvirinae stack works to inhibit those same inflammatory pathways (which he hypothesised the Herpes virus as a possible cause for POIS) but was created for those who can't go on a vegan diet (a diet devoid of AA which triggers one of the POIS inflammatory pathways according to him). He hypothesised you can stop AA inflammatory pathway (temporarily) through Betaherpesvirinae stack, even if consuming AA.
The Betaherpesvirinae stack has more pharmaceuticals so I would be more cautious taking long-term and make sure you take his drug detox recommendations along with it.
You could try both and just see what works. His intention with these stacks was to improve/fix POIS symptoms, not cure. His immune competence therapy (broad-spectrum pathogen load reduction) (https://poiscenter.com/forums/index.php?topic=3151.msg31889#msg31893) was intended as a potential cure.
Also, after the Cascade stack stopped being effective for you, could you fix it again ? Could you verify your theory on Omega 6 ?
Yes that's correct to some degree. When I first begun taking SAMe, it felt like a miracle. It was like an off switch for my entire condition, including my food sensitivities. This lasted around 3-4 weeks until symptoms began emerging again. For whatever reason, it stopped working at 100%. I tried lots of different methylation nutrients, supporting minerals, buffer nutrients like folate etc but nothing worked 100% long-term. But I do think it did "permanently" top up my methylation such that I no longer need to constantly take B vitamins, eggs (choline), etc. Before SAMe, I always felt an enormous difference before and after re my B complex, eggs, etc. Like I needed to take the B complex daily to feel good. These days I don't really feel the need as much for methylatio nutrients, apart from eggs and red meat for POIS.
For what it's worth tho, my sensitivties and POIS definitely seemed to permanently improve since the SAMe, but it's hard to put a number on exactly how much.
I also don't know about SAMe's long-term safety so I am personally hesitant to continue taking it long-term as well, even tho I do think it benefited me.
Nanna1's stack also taught me how important D3 serum is. D3 serum is king.
Re the Omega-6, I honestly have no idea. It's too difficult to test. These days I stick to a low seed oil diet given that I eat so much saturated and animal fat. Vegetable oils oxidise cholesterol apparently. The science is a bit controversial, but I definitely don't want to eat both concurrently. I'm also seeing a low-carb Dr here in Aus who advises to keep Omega-6/seed oils virtually to zero. I also personally haven't responded at all to Omega-3, hasn't made any impact on my POIS whatsoever but for others it's been a gamechanger.
Thanks for the info. I don?t get why you don?t take the Betaherpesvirinae Stack as you reponded to the Cascade stack ?
I understand that Cascade Stack does not work well with meat as meat contains AA.
But Betaherpes should work fine for you ?
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Thanks for the info. I don?t get why you don?t take the Betaherpesvirinae Stack as you reponded to the Cascade stack ?
I understand that Cascade Stack does not work well with meat as meat contains AA.
But Betaherpes should work fine for you ?
Tbh I should try the pharmeceuticals purely from an experimentive/insight POV. The relief I get from my own method is already significant for POIS. I can pretty much release whenever I want without problem, but I do still experience a distinct shift in my state for a good 12-24hrs. Back then I was mostly trying to fix my food sensitivities which coincide with my POIS as I was desperate to get off the animal-based diet I was on back then. These days I have seemingly hit a new level of satisfaction with diet being on ketogenic and am happily tolerating lots of standard keto foods inc. veggies, dark choc, etc with the help of Monolaurin. My energy, hormones, and overall diet satisfaction has improved dramatically since going keto. Something I really struggled with while I was on animal-based, despite it being a huge breakthrough for my POIS.
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Thanks for the info. I don?t get why you don?t take the Betaherpesvirinae Stack as you reponded to the Cascade stack ?
I understand that Cascade Stack does not work well with meat as meat contains AA.
But Betaherpes should work fine for you ?
Tbh I should try the pharmeceuticals purely from an experimentive/insight POV. The relief I get from my own method is already significant for POIS. I can pretty much release whenever I want without problem, but I do still experience a distinct shift in my state for a good 12-24hrs. Back then I was mostly trying to fix my food sensitivities which coincide with my POIS as I was desperate to get off the animal-based diet I was on back then. These days I have seemingly hit a new level of satisfaction with diet being on ketogenic and am happily tolerating lots of standard keto foods inc. veggies, dark choc, etc with the help of Monolaurin. My energy, hormones, and overall diet satisfaction has improved dramatically since going keto. Something I really struggled with while I was on animal-based, despite it being a huge breakthrough for my POIS.
Hi Warrior,
Thanks for sharing.
What I had in mind is that the Betaherpes from my understanding is compatible with other methods to achieve 100% relief and the acid arachidonic blockers seemed to be efficient on you.
I?m currently trying to figure out if the acid arachidonic blocker methods (the 2 nanna?s stack) are efficient for me as well so that I can combine them with my current treatments to try and maximize relief.
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I also produced a simplified explanation of Nanna s theory using Chatgpt, I am posting it below as it could help some people getting the principles:
This theory on Post-Orgasmic Illness Syndrome (POIS) suggests that POIS symptoms result from a complex chain of biological events referred to here as the ?POIS Cascade starting with overstimulation of α1-adrenergic (α1A) and histaminergic (H1) receptors. This cascade triggers a rapid release of arachidonic acid (AA), leading to the production of inflammatory molecules, which then cause the flu-like symptoms associated with POIS.
Key Points of the Theory
1. Role of Norepinephrine and the α1-Adrenergic (α1A) Receptor:
- During orgasm, norepinephrine levels temporarily rise. In people with POIS, this norepinephrine surge overactivates the α1A receptor.
- Stimulation of α1A activates enzymes Phospholipase A2 and C, which release arachidonic acid (AA) from the cell membrane.
2. Release of Arachidonic Acid (AA):
- The release of AA, a pro-inflammatory omega-6 fatty acid, activates enzymes 5-LOX and COX-2, which convert AA into inflammatory prostaglandins (such as prostaglandin E2), causing POIS symptoms.
3. Similar Mechanisms with Histamine and Glutamate:
- External triggers (e.g., allergens, food) may produce POIS-like symptoms through different receptors (H1 for histamine, NMDA for glutamate), similarly leading to AA release and inflammation.
Intervention: Blocking the POIS Cascade
The theory proposes blocking three main steps in the cascade to prevent POIS:
1. Reduce α1A and H1 Receptor Expression:
- SAM-e (S-adenosyl-methionine) is suggested to regulate α1A expression through methylation processes, which help stabilize the cell membrane and reduce AA release.
- Activated Vitamin B1 (Benfotiamine) can help downregulate H1 receptor expression, reducing histamine-triggered inflammation.
2. Inhibit NF-kB and Inflammatory Cytokines:
- Vitamin D3 inhibits NF-kB and COX-2, reducing the production of inflammatory cytokines (like TNF-α, IL-1B), which contribute to POIS symptoms.
3. Decrease Arachidonic Acid Release and Inhibit Pro-Inflammatory Enzymes:
- Omega-3s (EPA and DHA): EPA and DHA can reduce AA production by limiting its integration into cell membranes, thereby preventing the formation of inflammatory prostaglandins.
- The author also reduces dietary AA (avoiding omega-6-rich meats), lowering the amount of AA available for release.
Supplement Strategies
The author suggests two supplement protocols to manage POIS, each tailored to different situations:
1. The POIS Cascade Stack:
- This includes daily supplements (SAM-e, EPA, DHA, Vitamin D3, and various B vitamins) to inhibit the inflammatory cascade and maintain a biochemical environment less prone to triggering POIS symptoms.
2. The Betaherpesvirinae Stack:
- This protocol addresses a potential link between POIS and viral reactivation (such as CMV or HHV-6). It involves immune regulators and antioxidants (Vitamin D3, N-acetylcysteine, and selenomethionine) to prevent virus-related inflammation, used before sexual activity.
Conclusion and Insights
This theory suggests that POIS may result from an exaggerated inflammatory response, with arachidonic acid release playing a central role. By targeting each step in this cascade with supplements that act on receptors, inflammation pathways, and AA availability, the author reports relief from POIS symptoms.
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Thanks for this. I found this simplified explanation by Physi / Chatgpt useful. I've tried to read Nanna's original post quite a few times but I found a lot of it difficult to follow.
I wonder what made Nanna think that the rapid release of arachidonic acid is associated with pois? (I'm not saying he's wrong, I just find it interesting).
One thing I've never tried is SAMe. I've never taken it because it's had a few negative reports in the media and it's expensive. Anyone got experience with SAMe? It seems to be an essential component of Nanna's pois treatment?
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Hi Sisyphus,
You?re welcome.
I think I have read on one of Nanna?s post that Sam e was an important component.