POIS treatment: theory & supplement stack

[Muon]

Has anyone on this forum been tested for PGE2?

[taurusthree]

Hey nanna1, thanks for your efforts!

I have a question about the SAM-e dosage: is it total 200mg a day, or 400mg (2x 200mg). From the way the list is constructed I can assume it is 200mg (2x 100mg), however this seems like a very small dosage (given SAM-e has low oral bio availability) also it's not possible to find 100mg tablets anywhere (and breaking them is not an option).

[Vandemolen]

I want to report that Nanna’s stack didn’t work for me. But I only use it for 10 days. Nanna said that you have to use it for 3 or 4 weeks. So I will try about 2 or 3 weeks again. I was also already a bit sick because of my allergy of Cefuroxim. I finished the cure on Thursday. So why did I try yesterday? That’s because Wednesday I have an appointment with my POIS doctor. I thought if it worked I could try it Monday again to be sure it works for me. And then I could tell my POIS doctor. When it’s sure that it worked for me he would take it more serious.

I will report when I tried it again. Now my fingers, feet and skull are very dry. My troath, mouth, tongue and nose are dry. Niacin didn’t work for me but at least it helped a bit against a dry mouth and nose. There is also another thing. I also over masturbated. For more than 4 hours. Maybe it doesn’t work that long? Doing it for this period is also unhealthy for a man without POIS.

Nanna, could my shortage of IgM be the reason why your stack did not work for me? I am in a POIS state since I tried this stack.

[nanna1]

Hi taurusthree, each dose listed in the original post is per serving. So SAMe 2x(200mg) = 400mg per day. I hope that helps.

Hi Vandemolen,

Nanna, could my shortage of IgM be the reason why your stack did not work for me? I am in a POIS state since I tried this stack.

There seems to be a pattern emerging in the Medical Data/test thread show immunodeficiency in many of us POISers.

A few patterns in the data:
--4 of us have low neutrophil counts (nanna1, quotz, BluesBrother, certainlypois2).
--3 of us show normal neutrophil levels (Muon, Muon's brother, Nas).
--1 of us show low monocyte levels (quotz)
--1 of us show low Natural Killer cell (NK cells) levels (muon)
--1 of us show low lymphocyte levels (muon)
--1 of us show lymphocytes do not increase in response to lung infection (aswinpras06)

  I am only showing data of people who self-report, but Hopeoneday has also found several cases of neutropenia in POISers posted elsewhere. Immunodeficiency diseases are rare (low prevalence, post), so this seems very interesting. Most of the data is on Complete Blood Counts (CBC, neutrophils), but I think Muon's low NK cell levels is the most interesting result so far. This is because NK cells are the primary virus killers of the immune system. These immune deficiencies are all associated with the innate immune system. The innate immune cells (monocytes, neutrophils, NK cells) are the first responders to a harmful event (infection, cancer, poison, etc...). If the innate immune system fails, then the adaptive immune system (T cells, B cells, etc...) takes over and tries to control the harmful event.

  I mention all this because low immunoglobulin levels are sometimes used to measure immunodeficiency diseases. But this is usually done using the IgG subclasses (IgG1, IgG2, IgG3, IgG4). Kurtosis and Muon have written a few good post on immunoglobulins. I don't see any patterns in the POISer data related to IgM, and I do not see how this result would affect the stack. Immunoglobulin are mostly related to the innate and adaptive immune systems. But both stacks that I propose (vegan diet/POIS Cascade stack and Betaherpesvirinae stack) are manipulating the intrinsic immune system (arachidonic acid cascade, NF-kB, etc...). The Betaherpesvirinae stack directly suppresses the intrinsic immune system, but the POIS Cascade stack is suppose to reduce inflammation without suppressing any immune function. There could be a connection between IgM levels and the stacks, but I do not see any direct connection at this point in time. A test that measures NK, T and B cells would probably be more informative (Lymphocyte Subset Panel Test).

  I hope I understood what you were asking. Let me know if you have any additional information that might be useful. I am always learning new things from you guys. 

[Muon]

I've also taken B1 a lot, in different forms, and I found it highly useful. But ... indeed, you can build a tolerance. And I have found that after a while of taking 300 mg a day, I got problems breathing. As in: I had to think about breathing, otherwise it felt like my body/brain just didn't do it automatically. Quite scary. At one point I was afraid to go to sleep. Fortunately, all turned out well, but I'm more careful with B1 now.

It's a common problem on the DINET forum: ''Since last summer I have had a hard time breathing on and off. Some days it feels like my body is not breathing on its own.''

Some other note I want to add, is that my slightly elevated 11b-PGF2-alpha could be due to increased AA production. If you take a look at the AA precursors you will end up at lipids. Perhaps there is something wrong with lipid metabolism.

[Vandemolen]

Thank you Nanna. I am going to an immunogolist within a month. I hope he will do more blood tests. I will report in the blood test topic.

[demografx]

Unnecessary to re-play a huge post just to report an upcoming Dr visit.

[demografx]

I think I will be pointing my muonic cannon towards Chile today .

Pointed towards Santiago, Chile

[taurusthree]

Hi taurusthree, each dose listed in the original post is per serving. So SAMe 2x(200mg) = 400mg per day. I hope that helps.

Alpha-GPC for example (if chosen as the methyl donor), is currently listed as to be taken in 1.2g dosage. So is it 2x 1.2g = 2.4g? I doubt it, since later in the first post you suggest to

work your way up to a twice daily dose at 600mg over the course of one week.

And the latter, I assume, is the final dosage of Alpha-GPC.

[nanna1]

And the latter, I assume, is the final dosage of Alpha-GPC.

Hi taurusthree,
  Yes, you are correct! 600mg 2 times per day = 1.2g per day. I am sorry for my poor communication skills. Since this is a common question, I have corrected this in the original post. Also please see this conversation on Alpha-GPC for more details (post). Thanks 

[taurusthree]

Thanks for clarifications!

Almost 3 weeks on the daily total intake of below:
Vitamin B6 - 10mg;
Methylfolate - 1000mcg (will going to cut down the intake soon, currently have deficiency);
Vitamin B12 - 1000mcg;
SAM-e - 400mg;
Vitamin D - 5000IU (will going to cut down the intake soon, currently have deficiency);
Betaine - 1.5g (going to double the dose);
Vitamin C (1000mg) (can probably be beneficial for my joints and may support the immune system);

My story:
26, male. I have (and probably always had) POIS (mild - 1st day: IBS, watery eyes, random itching, brain fog and other cognitive issues; 2nd day: cognitive issues only), trio of [MCAS-POTS-hEDS] (probably inherited from maternal side), ADHD (seems to be distinctly inherited from paternal side), beta-Thalassemia minor (which potentially can contribute to the folate deficiency), allergies.
For more than a year was taking 25mg of SSRI Sertraline (which magically cured my chronic rhinitis, also helped me with my oversaturated emotions, reduced POIS by half, and overall gave me an energy). Didn't try stimulants for my ADHD, since those are banned in my country.
In 2017 I did a test for folate and homocysteine because Promethease suggested I have 2 of the MTHFR mutations (heterozygous). Though I am sceptical about the MTHFR stuff I decided to give a try. Everything was within the normal range. However a month ago the same test revealed I have low folate levels and pretty high homocysteine. My guess is - the activating antidepressant caused that. Also, recently discovered I have low levels of Vitamin D.

So I saw your post and decided to try the stack. 3 weeks after I can report the following:
1. POIS is way milder, mostly cognitive symptoms (could be my ADHD);
2. Gum bleeding during washing my teeth stopped (special thanks for this, I was really upsed by that for more than few years);
3. Overall less hEDS related pain (could be related to the antiinflammatory effect of Vitamin D, also to SAM-e/ methylation antidepressant action);
4. Less local infections (including complete elimination of feet fungus).

Your theory (alpha1 receptors overexpression) can potentially explain the following:
a. How SSRI helped with my chronic rhinitis. In my opinion the mechanism is following: [serotonin reuptake] --> [better parasympathetic tone] --> [less sympathetic tone] --> [less alpha1 receptor firing] --> ... --> [less inflammation];
b. The connection between MCAS, POTS and hEDS. So one of the teories is that hEDS-ers have elastic vessels, which don't hold up during the orthostatic stress induced higher heartbeat (which elevates further, which is the manifestation of POTS). Can't this over time potentially cause an overexpression of alpha1 receptors, so the vessels will be supported as much as possible? And this in turn may induce inflammation from slightest elevations of noradernaline - MCAS-ish symptoms.

[nanna1]

Hi taurusthree,

  Your stack looks good! But I assume you are skipping the omega-3/CLA portion. That's fine as long as you are improving. I am glad to hear about your results. I also like that you are customizing dosage based on your personal vitamin deficiency. Your post will be helpful for others who may have similar vitamin deficiencies and medical test results.

  I thought your explanation of the alpha1-receptor overexpression is brilliantly stated. When I first read your post, I did not know the exact mechanism for how the a1A-adrenergic receptor would become overexpressed. I only knew what the its properties were and the similarities with what is known about POIS. You actually brought up some ideas that I did not think of. For example, your explanation could be similar/related to Hyperadrenergic POTS. Also, the connection you made to hEDS makes a lot of sense. I will try to explain what I think you are asking/saying. But please add comments and corrections so that I understand fully what you are proposing. I will start from the perspective of POIS, but I assume the following principles could also be applied to Hyperadrenergic POTS, intense excersise or intense fear.

b. The connection between MCAS, POTS and hEDS. So one of the theories is that hEDS-ers have elastic vessels, which don't hold up during the orthostatic stress induced higher heartbeat (which elevates further, which is the manifestation of POTS).

  During sexual activity vasodilation increases (for example: erection and sex flush). Epinephrine (adrenaline) and norepinephrine (noradrenaline) is released during orgasm to produce ejaculation (Ref).

Figure from: Specificity of the neuroendocrine response to orgasm during sexual arousal in men. (U Hartmann, et al, 2003)

This noradrenaline release also causes Increased Heart Rate (IHR) similar to tachycardia. This is a normal part of sex physiology.

Figure from: Endocrine response to masturbation-induced orgasm in healthy men following a 3-week sexual abstinence (U Hartmann, et al, 2001)

  If the total blood volume in the body is constant, an increased heart rate (IHR) means that the heart is pumping with more force and producing larger pulses in blood pressure. This IHR puts greater stress on dilated blood vessels than it does on constricted blood vessels.

Figure from: HyperPhysics: Capillary Walls

  From the cylinder surface-tension equation (Laplace's Law): T=P*R, increasing the radius R also increases the surface tension stress T. So for a given blood pressure P, vasodilation (larger radius R) produces a higher surface tension stress (T) on the the blood vessel wall than vasoconstriction (smaller radius R). This increased tension can cause shear stress injury to the vasodilated blood vessels called balloon injury.

Figure from: HyperPhysics: Danger of Aneurysms

Can't this over time potentially cause an overexpression of alpha1 receptors, so the vessels will be supported as much as possible?

  As you have stated, vasoconstriction supports and protects the vessels. In response to ballon injury, norepinephrine-induced vasoconstriction protects vessels from undergoing more balloon injury than has already occurred.

"This is the first study to demonstrate enhanced adrenergic neurotransmission after balloon injury. The facilitation of adrenergic neurotransmission may be due to increased local concentrations of angiotensin II..." -Vascular Injury Augments Adrenergic Neurotransmission (RC Candipan, et. al.,1994)

 This may lead to alpha1-receptor over expression (Angiotensin II induces transcription and expression of alpha 1-adrenergic receptors in vascular smooth muscle cells, ZW Hu, et. al., 1994),  This overexpression causes vasoconstriction (reducing the vessel radius R) which results in reduced surface Tension stress (T = P*R, Laplace's Law) at the location of injury.

And this in turn may induce inflammation from slightest elevations of noradernaline - MCAS-ish symptoms.

  One side-effect of injury-induced alpha1-receptor over-expression can be chronic inflammation:
"Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the production and release of pro-inflammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alpha1A-adrenoceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alpha1-adrenoceptors to increase the production of the pro-inflammatory cytokine...These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome...Thus, activation of aberrantly-expressed alpha1-adrenoceptors may contribute to chronic inflammation and pain." -Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury (PD Drummond, 2014)

  One of Dr. Waldinger's POIS studies noted that pre-mature ejaculation seemed common (56%, error=+-7%) among POIS patients being studied (MD Waldinger, et. al., 2011). Ejaculation is caused by norepinephrine binding to the alpha1-Adrenergic receptor (Ref1, Ref2). If there is vascular or smooth muscle injury in the reproductive system causing alpha1A-receptor overexpression, this could explain the pre-mature ejaculation symptoms observed by Dr. Waldinger.

  It is an interesting coincidence that exercise causes vasodilation partly by down regulating the alpha1-adrenergic receptor.

"a1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, a2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity."
-Exercise attenuates alpha-adrenergic-receptor responsiveness in skeletal muscle vasculature (JB Buckwalter, et. al., 2001)

Exercise and fear also produce IHR by releasing epinephrine (adrenalin) and norepinephrine.

If this could explain parts of the POIS-trigger, I still would have a few questions:

• Where is the vascular/balloon injury located?
• What caused the original injury?
• Why does the injury not heal now?

In terms of question 1, POIS symptoms are top-bottom asymmetric in everyone but also left-right asymmetric in some. So the inability to heal properly would have to be localized to specific vessels in the body, while not affecting healing in other blood vessel locations. I suspect that the answers to questions 2 and 3 are the same. Whatever would cause the original injury is also probably keeping it from healing, unless the original injury was a random event.

If you have any corrections or other thoughts, please share. That was interesting!

[aswinpras06]

Another nice finding from you, Nanna1.

If chronic injury to blood vessels is causing inflammation the most likely place is likely to be the gut vessels.

Most of us have gut problems upon orgasm and it takes a while to get healed and it never heals completely.

Glutamine,aloe juice/jel, change in diet and gut healing foods helps many of us.

So if there is some unhealed inflammation, most likely it should be in the blood vessels of the gut.

[Hopeoneday]

Yeah , it could be a link with gut vesels, Muon posted link of people with
dysautonomia, its tightly conected to our symtopmes like pots etc,
and there some people is diagnosed with stomach aneurism, could be
posible that some of us hawe it, beside odher gut isues.
https://poiscenter.com/forums/index.php?topic=1417.msg13114;topicseen#msg1311

Pois damage our nerwes, cronic inflamation,
that folow systematic disbalance, gut mobility not
working, lack of nutrinents, thats why b vitamins works for some...

[Nas]

Good discussion guys!
I wonder do Habibou's tests correlate with this theory?

This theory has lot of sens for me , but my adrenalin results are actually really low... ! 
I will post again my neurotransmitters results :

  January 2011

Blood :
-adrenaline           <0.50 nmol/l         < 1.00
-noradrenaline        8.53 nmol/l       < 4.00                              1443 ng/l      < 675
-dopamine            <0.50 nmol/l         <1.00


Unrina during 24h :

-adrenaline       0.02 umol/l           < 0.10
-noradrenaline   0.42 umol/l          < 0.50
-dopamine        1.34 umol/l           < 3.00

All the blood tests were done 2 hours after an O.
The red standards are the unusual ones !

January 2012 :
ONLY Urina test, morning 10 hours after an O:

DOPA                      91.50 ug/g  (160 - 240)
34DOPAC                       0.40 mg/g    (0.70 - 4.00)
HVA                          1.90 mg/g    (2.43 - 5.20)
NORADRENALIN          10.30 ug/g   (15.70 - 34.30)
MHPG                          1.50 mg/g  (1.38 - 4.15)
VMA                            1.60 mg/g  (2.10 - 3.85)
ADRENALIN                  0.98  ug/g  (1.27 - 6.10)
SEROTONIN                62.40  ug/l   (61.50 - 116.80)
5HIAA                        2.30    mg/g (2.03 - 4.26)
HVA5HIAA                  0.83            (1.25 - 2.56)

[Nas]

I guess alpha-1 blockers should test if this theory holds merit.

[nanna1]

Good discussion guys!
I wonder do Habibou's tests correlate with this theory?

Good question! The main thing that stands out to me from Habibou's test are his high norepinephrine levels in the blood test 2 hours after orgasm.

January 2011

Blood :
-adrenaline           <0.50 nmol/l         < 1.00
-noradrenaline        8.53 nmol/l       < 4.00                              1443 ng/l      < 675
-dopamine            <0.50 nmol/l         <1.00

Neurotransmitters are released in an activity dependent manner depending on what you are doing or thinking. So the levels should rise and fall (fluctuate) fairly quickly. Norepinephrine levels should not be elevated for two whole hours. Maybe the levels fell right after orgasm but then rose again right before the blood test. I started a thread that shows the endocrine response for these neurotransmitters here (Neuroendocrine responses to arousal and orgasm).

  Assuming that his norepinephrine levels remained elevated for at least 2 hours, one way of interpreting Habibou's neurotransmitter test is that he has reduced functioning of his Aldehyde dehydrogenase (ALDH) enzyme (see dopamine degradation pathway, DOPAC, HVA). I would rule out monoamine oxidase (MAO) dysfunction because his serotonin and 5HIAA are normal. I would also rule out catechol-O-methyltransferase (COMT) dysfunction because his DOPAC levels are low and his MHPG is normal. DOPAC does not depend on COMT (diagram1) but MHPG does diagram2). The diagram below shows the enzymes responsible for the 3-Methoxy-4-hydroxyphenylglycol (MHPG) and Vanillylmandelic acid (VMA) parameters in his urine test:

  Decreased ALDH is most common among southeast Asians and is responsible for Asian Flush. I have a friend that goes through this every time they drink alcohol. This might explain his high blood norepinephrine levels, and it could also explain his low urine DOPAC, VMA, HVA and HVA:5HIAA ratio.

  Since COMT is a methyltransferase, taking a methylation stack (SAMe, folate, lecithin, etc...) might help remove dopamine metabolites quicker. I don't have an explanation for Habibou's low urine epinephrine and norepinephrine levels, but there are many other neurotransmitter metabolites that are not measured in his test. Also it is important to remember that urine is bodily waste. I could be wrong, but I don't think that urine levels accurately describe what is going on in the blood as much as a blood test.

  In terms of the idea Taurusthree shared and I wrote about where alpha1-adrenergic receptors are over-expressed to support/protect the blood vessels through vasoconstriction, it seems that inhibiting the alpha1-receptor with an alpha-blocker would cause additional injury to the vessel. When orgasm happens, alpha1-dependent vasoconstriction at the site of injury should occur at the same time as the increased heart rate/blood pressure because norepinephrine levels control both these events. Moreover, the amount of vasoconstriction should be in proportion to the heart rate because both of these are in proportion to norepinephrine levels. So, in theory, the alpha1-receptor should be protective and vasoconstriction should be protective. Relevant bio-markers to test if there is vascular balloon injury are angiotensin II, endothelin-1 and possibly creatine kinase.

  However, when I get blood test (medical test), the nurse sticks a needle in my arm and punctures a vein in order to extract the blood. My vein heals quickly (<24 hours) without any POIS or systemic immune reaction. So I do not think that there is anything global wrong with my arteries or veins. But if alpha1-receptor overexpression is causing POIS problems, it could be a possibility that norepinephrine and alpha1 are also triggering something else that is locally latent in that portion of the blood vessel and preventing proper healing of the vessel. This is the reason that I asked the questions:

If this could explain parts of the POIS-trigger, I still would have a few questions:

• Where is the vascular/balloon injury located?
• What caused the original injury?
• Why does the injury not heal now?

I don't think this thread is the best place to discuss a lot of detailed theory since many POISers here are rightfully interested in stacks. So I would prefer to discuss more detailed theories of POIS on other threads. Thanks Nas for your question!

[Nas]

Thanks for the detailed reply Nanna, as usual.

If you want start another thread and we can discuss this all right there. I don't to do it my self since I don't even know what would I call that thread.

I guess when it comes to the Alpha-1 blocker inquiry, Taurusthree mentioned that this constant over-expression is what leads to these inflammatory symptoms; MCAS-like symptoms. So perhaps the injury itself won't heal but the systematic symptoms can be better dealt with? Maybe I'll try an alpha-1 blocker and see if it does anything at all.

[Nas]

Nanna, I also wish in the future if you tack this, this is written by Waldinger:
''The lack of a local genital skin reaction after ejaculation, but the occurrence of multiple complaints after ejaculation, and the findings of the hyposensitization treatment suggest that in POIS immunologic reactions occur due to repeated close contact during ejaculation between seminal peptides and circulating T-lymphcytes. This leads to a systemic reaction with multiple physical and cognitive complaints.''

I think we have theorized many things that POIS can be. But we rarely paid attention to what Waldinger himself thinks. After all he worked closer with POIS than anyone of us.

I feel like this comment is his theory but incredibly summarized, and I wish it gets better explained. If POIS is actually an auto-immune disease, then how do we get systematic symptoms instead of localized ones?

[whateverestest]

Do you guys think it should work on Emotional symptoms like Social Anxiety? I get this for a couple of days after O, I'm totally less self-confident then...

What do you think guys?

Nanna1?

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