Author Topic: POIS treatment: theory & supplement stack  (Read 167709 times)

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #40 on: August 11, 2017, 09:36:31 PM »
Thanks Romies for the gene testing info! Did you mean to write http://geneticgenie.org/? I'll definitely check it out.
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/

romies

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Re: POIS cure: theory & supplement stack
« Reply #41 on: August 12, 2017, 12:45:34 PM »
Thanks Romies for the gene testing info! Did you mean to write 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 Some of the interpretation from geneticgenie is outdated/inaccurate.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.

Quantum

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Re: POIS cure: theory & supplement stack
« Reply #42 on: August 19, 2017, 09:37:45 AM »
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.
« Last Edit: August 19, 2017, 09:59:28 PM by Quantum »
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Rinat

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Re: POIS cure: theory & supplement stack
« Reply #43 on: August 19, 2017, 09:24:12 PM »
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!
« Last Edit: August 20, 2017, 12:16:56 AM by Rinat »

ThisType

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Re: POIS cure: theory & supplement stack
« Reply #44 on: August 19, 2017, 10:20:08 PM »

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]
« Last Edit: August 20, 2017, 01:41:04 PM by ThisType »

POISse

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Re: POIS cure: theory & supplement stack
« Reply #45 on: August 20, 2017, 10:21:20 AM »
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?

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #46 on: August 20, 2017, 07:59:04 PM »
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, 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
2.   POIS cure: theory & supplement stack
3.   Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model
4.   Positive Feedback between Acetylcholine and the Neurotrophins Nerve Growth Factor and Brain-derived Neurotrophic Factor in the Rat Hippocampus
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
« Last Edit: August 20, 2017, 09:36:29 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/

Quantum

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Re: POIS cure: theory & supplement stack
« Reply #47 on: August 20, 2017, 08:14:29 PM »
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).   
You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #48 on: August 20, 2017, 10:53:01 PM »
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). Asprin is a pretty cheap COX inhibitor. Grapefruit juice and pygeum 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)


  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 (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: 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! :)
« Last Edit: August 20, 2017, 11:16:32 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/

Rinat

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Re: POIS cure: theory & supplement stack
« Reply #49 on: August 20, 2017, 11:53:57 PM »
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)
« Last Edit: August 21, 2017, 01:39:00 AM by Rinat »

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #50 on: August 28, 2017, 08:14:34 PM »
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!
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 #51 on: August 28, 2017, 08:34:51 PM »
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:

Quote
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) [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].
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.

  So flavonoid supplementation is primarily a type of hormone therapy [14]. This is why I cautioned against taking flavonoid extracts in the original post. At high concentrations, (achieved through extracts) some become estrogenic. I suspect that the deleterious effect that curcumin has on sperm[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 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 studied the 2nd reference, it appears that mistletoe and damiana had the largest progesterone/estrogen stimulation ratios (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.

Thanks again for sharing the article. 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)
2.   Estrogen and progestin bioactivity of foods, herbs, and spices. (1998)
3.   The Effects of Progesterone on Glial Cell Line-derived Neurotrophic Factor Secretion from C6 Glioma Cells
4.   Progesterone, BDNF and Neuroprotection
5.   Progesterone inhibits mast cell secretion. (2006)
6.   Role of female sex hormones, estradiol and progesterone, in mast cell behavior (2012)
7.   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)
11.   Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells.
12.   Copper toxicity, oxidative stress, and antioxidant nutrients (2003)
13.   Effect of estrogen on serum and tissue levels of copper and zinc.
14.   Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin
15.   Can curcumin provide an ideal contraceptive? (2011)
16.   Effects of Licorice Extract on Sperm Motility of Chilled Stored Ram Semen
17.   Improved In Vitro Fertilization Ability of Mouse Sperm Caused by the Addition of Licorice Extract to the Preincubation Medium
« Last Edit: August 31, 2017, 08:42:15 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 #52 on: August 29, 2017, 08:45:15 AM »
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.

« Last Edit: August 29, 2017, 08:51:25 AM by Quantum »
You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #53 on: August 30, 2017, 11:48:50 PM »
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.
« Last Edit: August 31, 2017, 12:12:55 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/

romies

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Re: POIS cure: theory & supplement stack
« Reply #54 on: August 31, 2017, 03:40:03 PM »
  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). Asprin is a pretty cheap COX inhibitor. Grapefruit juice and pygeum 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.

romies

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Re: POIS cure: theory & supplement stack
« Reply #55 on: August 31, 2017, 03:59:31 PM »
  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


romies

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Re: POIS cure: theory & supplement stack
« Reply #56 on: August 31, 2017, 04:16:16 PM »
  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: 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.

Nas

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Re: POIS cure: theory & supplement stack
« Reply #57 on: September 02, 2017, 01:13:21 AM »
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
« Last Edit: September 02, 2017, 01:17:38 AM by Nas »

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #58 on: September 02, 2017, 12:40:23 PM »
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). I know that is a really small amount. According to the National Institutes of Health, the upper B6 limit is 100mg per day. 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) or a combo pack like (NOW SAMe 200 mg,60 Tablets). 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.

« Last Edit: September 02, 2017, 01:15:59 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/

romies

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Re: POIS cure: theory & supplement stack
« Reply #59 on: September 02, 2017, 05:18:14 PM »
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). Also considering the half-life of quercetin is 11hrs, 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).

To set the right context, skin contact with thermal paper (receipts etc) for 4mins gives you a dose of BPA (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) [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.

  So flavonoid supplementation is primarily a type of hormone therapy [14]. This is why I cautioned against taking flavonoid extracts in the original post. 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 showing quercetin inhibits progesterone production.

I suspect that the deleterious effect that curcumin has on sperm[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). 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 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 studied the 2nd reference, it appears that mistletoe and damiana had the largest progesterone/estrogen stimulation ratios (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)

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.