POIS treatment: theory & supplement stack

[Iwillbeatthis]

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.

[Iwillbeatthis]

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.

[Bob Morane]

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
I have not tried it. I am just answering your question.

[Hakira117]

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.

[Lihua]

  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).

  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 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, 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). 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].

  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.
  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 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]. D3 accomplishes this by inhibiting the production of inflammatory cytokines such as TNF-a, IL-1B, IL-6, etc... [schematic diagram]
  (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).

For a literature review of POIS related research see POIS literature review:

-----------------------------------------

  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, RefSE2). More details on how herpes viruses may initiate POIS can be found here (link). "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 (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]

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!

[hapl]

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.

[Muon]

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

[sammy]

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!

[swell]

Where is nanna1 folks, I truly miss nanna1's presence here, he has contributed a wealth of knowledge here (and to me).

[demografx]

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

[demografx]

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).

[swell]

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).

[demografx]

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

[swell]

Thanks Demo.

[johnmic]

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

[Warrior]

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.

[Warrior]

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.

[Thomas]

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.

[Mr Raba]

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).

  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 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, 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). 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].

  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.
  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 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]. D3 accomplishes this by inhibiting the production of inflammatory cytokines such as TNF-a, IL-1B, IL-6, etc... [schematic diagram]
  (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).

For a literature review of POIS related research see POIS literature review:

-----------------------------------------

  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, RefSE2). More details on how herpes viruses may initiate POIS can be found here (link). "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 (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]

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!

[Warrior]

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.