Author Topic: POIS treatment: theory & supplement stack  (Read 181316 times)

Rinat

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Re: POIS cure: theory & supplement stack
« Reply #60 on: September 13, 2017, 12:55:05 PM »
   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
 
« Last Edit: September 13, 2017, 12:58:07 PM by Rinat »

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #61 on: September 14, 2017, 09:53:36 AM »
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 [1, 2].

  TMG and alpha-GPC are natural osmolytes 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, 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.
2. https://en.wikipedia.org/wiki/Histamine_N-methyltransferase
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Rinat

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Re: POIS cure: theory & supplement stack
« Reply #62 on: September 14, 2017, 11:00:38 AM »
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)
« Last Edit: September 14, 2017, 11:08:58 AM by Rinat »

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #63 on: September 14, 2017, 11:30:24 AM »
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.). 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.
« Last Edit: September 14, 2017, 12:00:45 PM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

LAPOISSE

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Re: POIS cure: theory & supplement stack
« Reply #64 on: September 26, 2017, 03:55:44 PM »
  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].
  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 (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]


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 (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 to reducing homocysteine and recycling SAM-e (see #2 in Homocysteine Cycle). 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 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). 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. Therefore, it may be just as important to reduce dietary omega-6 (AA) consumption. 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 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] (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 found in the environment [22]. However, it is important to point out that whole-herbs like licorice (contains quercetin) and tumeric do not appear to have this negative effect, 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 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)
2.   Norepinephrine stimulates arachidonic acid release from vascular smooth muscle via activation of cPLA2. (1998)
3.   Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism. (2013)
4.   Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms. (2004)
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)
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) also link to full article
16.   Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury.
17.   Antioxidant status and reproductive hormones in women during reproductive, perimenopausal and postmenopausal phase of life. (2014)
18.   Progesterone Inhibits Mast Cell Secretion (2006)
19.   Tryptophan metabolism, disposition and utilization in pregnancy (2015)
20.   Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor (2013)
21.   Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity.
22.   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

fathom

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Re: POIS cure: theory & supplement stack
« Reply #65 on: September 26, 2017, 04:37:59 PM »
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 [1, 2].

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #66 on: September 29, 2017, 12:59:12 AM »
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.
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #67 on: September 29, 2017, 02:03:13 AM »
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
  • there are 5 adrenergic receptors (alpha1/a1, a2, beta1/b1, b2 and b3 receptor)link
  • 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 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 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:". 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). 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) and Norepinephrine (A.K.A. noradrenaline) 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).

   Adrenaline and noradrenaline (epinephrine and norepinephrine) cannot cross the blood brain barrier. 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/ 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. :)
« Last Edit: September 29, 2017, 04:17:28 AM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Nas

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Re: POIS cure: theory & supplement stack
« Reply #68 on: September 29, 2017, 07:35:38 AM »
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

Michael218

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Re: POIS cure: theory & supplement stack
« Reply #69 on: September 29, 2017, 07:47:52 AM »
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.

Michael218

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Re: POIS cure: theory & supplement stack
« Reply #70 on: September 29, 2017, 05:35:20 PM »
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 :)

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #71 on: September 30, 2017, 05:11:42 AM »
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 for others who are also customizing the stack without omega-3. I hope this was useful.
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #72 on: September 30, 2017, 05:13:51 AM »
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. 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. CREA production consumes choline/betaine-TMG in the liver. And CREA supplementation spares the consumption of betaine by the homocysteine cycles 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) 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.

  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 (supplying three methyl-groups) is less expensive, being ~40% the cost per methyl-group of creatine (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 (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.
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 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.

  Creatine loading 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.
« Last Edit: September 30, 2017, 06:56:11 AM by nanna1 »
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
Find medical test: https://www.findlabtest.com/

Quantum

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Re: POIS cure: theory & supplement stack
« Reply #73 on: September 30, 2017, 07:01:11 AM »
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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Quantum

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Re: POIS cure: theory & supplement stack
« Reply #74 on: September 30, 2017, 07:05:05 AM »
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 )

« Last Edit: September 30, 2017, 07:08:49 AM by Quantum »
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nanna1

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Re: POIS cure: theory & supplement stack
« Reply #75 on: September 30, 2017, 11:05:17 AM »
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.
POIS clusters: 1,3,4,5,7
POIS criteria: 1,2,3,4,5
2 stacks that give me complete relief of POIS symptoms are listed here: POIS cure: theory & supplement stack
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Nas

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Re: POIS cure: theory & supplement stack
« Reply #76 on: September 30, 2017, 10:07:47 PM »
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

Nas

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Re: POIS cure: theory & supplement stack
« Reply #77 on: October 01, 2017, 03:14:09 AM »
Oh and the Bentofetamine is 250 mg capsuls, so I won't take them twice a day.
« Last Edit: October 01, 2017, 03:38:20 AM by Nas »

Michael218

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Re: POIS cure: theory & supplement stack
« Reply #78 on: October 02, 2017, 06:19:11 AM »
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!

Quantum

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Re: POIS cure: theory & supplement stack
« Reply #79 on: October 02, 2017, 07:51:46 AM »
Great results, Michael!   You are on the right track for sure, 80%-90% relief is excellent.
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