Author Topic: POIS treatment: theory & supplement stack  (Read 181307 times)

trusttheprocess

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Re: POIS cure: theory & supplement stack
« Reply #20 on: July 26, 2017, 02:56:03 AM »
Hey nanna1,

I've just read over your ideas on the inflammatory cascade involved in POIS and found it very informative.  I'll have to read further into these concepts, I'm also in the biomedical field and I've read a little about COX and AA pathways, a lot about histamine, methyl groups, and NDMA receptors, but not much about alpha-1-receptors, and your posts tie them all together very well.

I searched through the literature and found no mechanisms for antigen mediated POIS. The immune cells have access to the prostate. If there is enough antigen (or allergen) stored in the prostate to cause sickness, then I would expect the prostate would always be under attack by the immune system. I fully agree with the title rosscb used for the link you shared from kurtosis? post, ?The autoimmune theory is bogus?.

I have a small correction to make to this as it's important to my theory of POIS.  Quantum correctly stated earlier in this thread that white blood cells do not really reach the prostate, and most immune cells do not have access to the prostate.  The study "A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium" showed diffuse leukocyte infiltration and very restricted inflammatory cell penetrate into the prostate in rats, although the blood-prostate barrier in humans is referenced in several other publications.

Quantum also asked a very good question: "So, it could be possible that the sudden and heightened exposure to prostatic fluid and a potential prostatic antigen in it, following ejaculation, could trigger an auto-immune reaction otherwise not possible."  Yes, this is possible, and occurs in men with chronic prostatitis, as reported in the study "Autoimmune prostatitis: Evidence of T cell reactivity with normal prostatic proteins".  Furthermore urinary tract infection is a proven cause of autoimmune disease, with molecular mimicry and cross-reactivity proposed as the reason for the production of auto-antibodies, from the study "Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection".  These concepts, along with the presence of leukocytes in my urine following POIS, has led me to my theory that POIS is an infection of an immune privileged/"sanctuary site" of the urinary tract with a microorganism that exhibits molecular mimicry to normal human antigens.  I believe it to be a subset of chronic prostatitis, which researchers termed autoimmune prostatitis in one of the studies listed above.  Chronic prostatitis is a common syndrome that researchers believe is caused by a microorganism, which I think is likely fungi in most POIS sufferers due to our symptoms.  Below is the abstract of "Current treatment options in the management of chronic prostatitis", take a look at what is the first proven treatment listed.

"Chronic prostatitis is a disease with an unknown etiology that affects a large number of men. The optimal management for category III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unknown. The recent years have seen a significant increase in research efforts to understand, classify and treat CP/CPPS. Standard treatment usually consists of prolonged courses of antibiotics, even though well-designed clinical trials have failed to demonstrate their efficacy. Recent treatment strategies with some evidence of efficacy include: alpha-blockers, anti-inflammatory agents, hormonal manipulation, phytotherapy (quercetin, bee pollen), physiotherapy and chronic pain therapy. A stepwise, multimodal approach can be successful for the majority of patients who present with this difficult condition."

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #21 on: July 26, 2017, 06:23:21 PM »
Hi TrustTheProcess,

Thanks for commenting on the POIS cascade hypothesis and for taking the time to explain some details important to the Autoimmune Theory. I regret writing the sentences you show quoted from my July 24th post. I understand that people can be different and have different causes for their sickness. After so many years of suffering with a debilitating POIS, I am really excited and energized to share how I got cured (maybe too excited). I just want people cured, and I believe if we listen to our bodies and seek our greatest relief, we can all be our greatest fullest selves!
« Last Edit: July 26, 2017, 07:48:02 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 #22 on: July 26, 2017, 10:08:01 PM »
Very interesting discussion !

Thanks to Romies for the info about the enteric coated SAMe capsules.

Thanks TTP for his well-researched perspective on chronic prostatitis.

Thanks to nanni too, for his thorough and referenced discussion about the possible role of NMDA receptors in POIS.  Your references made clearer for me the link between the NMDAR activation and the AA neurotoxicity.

Stress management is good for about any health issue, and POIS is no exception, from my experience.  To add to your excellent explanation, I would mention that cortisol upregulates the TDO enzyme in the liver which further divert the tryptophan metabolism toward neurotoxic kynurenine products, diminishing at the same time the production of the most useful serotonin and niacin ( see at http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory )






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Quantum

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Re: POIS cure: theory & supplement stack
« Reply #23 on: July 26, 2017, 10:23:46 PM »

I?m looking for a cheaper source of alpha-GPC (choline). Maybe a bulk power. If find one please let me know. [Choline bitartrate messes up with my stomach.]


Have you considered using lecithin, which is cheap, and a good source of phosphatidylcholine ?
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Rinat

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Re: POIS cure: theory & supplement stack
« Reply #24 on: July 27, 2017, 01:56:25 AM »
Hi,Nanna1 :)
In advance I ask to excuse me for my English. I've read your theory about POIS. And I had questions:
1 How long has your treatment helped you?
2 You said that in a month you should stop taking B9. But how to do it if it is included in the SAM?
thank you,Rinat

romies

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Re: POIS cure: theory & supplement stack
« Reply #25 on: July 27, 2017, 12:34:28 PM »
Quantum and nanna1, thanks for the EPA/DHA dosage.  I am going to give high-dose EPA/DHA a try for 60 days and see how my POIS and exercise-induced fatigue may change.

nanna1, thanks for sharing your list of supplements. We are using many of the same brands.

On NDMA's role in AA release, there was one trial before by another forum member: https://poiscenter.com/forums/index.php?topic=2092.msg18484#msg18484

who gave memantine a try, but did not find much benefit.

I understand he could be on a different sub-type of POIS, and not related to NDMA. But many others could be still NDMA related. Just wondering if anyone has shown great response to memantine or other meds.

BTW, the first week on memantine is well known to cause brain fog etc, and is similar to the cognitive symptoms of POIS itself.

romies

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Re: POIS cure: theory & supplement stack
« Reply #26 on: July 27, 2017, 12:54:41 PM »
Regarding Flaxseed oil capsules, my reason for including them in my pre-pack is for the lignans in them, which are good antioxidants, and, mainly, have NMDAr blocking properties, so they protect against excitotoxicity, and thus reduces the POIS-induced anxiety and other CNS symptoms.

I do not consider flaxseed to be the most important part of my pre-pack, but who knows.  I could try only one capsule of flaxseed instead of 2, in my POIS pre-pack, and 2 capsules of omega-3 instead of one.   I did not made many changes or many new tests in the last two years.... if it's not broken, don't fix it ;)

That's quite interesting. I think the flaxseed oil I bought does not have much lignan in them. Lignan is a phytoestrogen, so I probably won't take a high dose.

Well, I see no harm at your dose of EPA/DHA. Very much agreed on "if it's not broken, don't fix it".

From month to month, I oscillate between adding supplements to my stacks and simplify them. I am in the adding mode right now, and probably will go into a subtraction mode in 3 months. lol

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #27 on: July 28, 2017, 01:11:50 AM »
  Thanks Quantum for the Lecithin recommendation. I was taking a daily Lecithin-betaine combo about a year ago and it was beneficial. But I really like alpha-GPC?s near 100% bioavailability. But if I cannot find a cheaper source, I may give Lecithin another try.

  To All, I highly recommend this article from Psychology Today on AA, DHA and EPA, which explains how to get the most out of an omega-3 supplement.
[What Are the Real Differences Between EPA and DHA? To reduce cellular inflammation, you need more EPA than DHA.] (https://www.psychologytoday.com/blog/in-the-zone/201204/what-are-the-real-differences-between-epa-and-dha)
P.S. The half-life of EPA in the body is roughly between 1.5 - 3 days depending on which form you buy, but it should not matter with daily supplementation. (must be taken with food)

  Relating to stress management, there is a really interesting 2010 study on lowering cortisol. Apparently, casual social interaction is a great way for men to lower cortisol/stress hormones unless it is with a woman that you find sexually attractive [1]. LOL!
(click to enlarge image)
  For those interested in receptor blockers of (norepinephrine, histamine, glutamate), it seems like you would have to take them before the orgasm to get any relief from POIS. I found this out from personal experience back when I used to take allergy meds (h1-histamine blocker). I used to wait until after I felt sick to take the h1H blocker, and it didn?t help me much. Then one day I took Claritin ~2 hour before the O and got partial (but not full) relief. The below study seems to suggest that alpha1 blockers must be taken before the O, because norepinephrine mediated AA release and enzyme up-regulation happens in a short window around the time of the O [2]. (legend: white squares->men watching a boring documentary; black quares->men watching a different type of film while administering self-coitus; time units=minutes)
(click to enlarge image)
  If there is not enough methyl donors to degrade histamine, h1H might continue to cause problems. But other than that, there shouldn?t be much receptor stimulated AA release 5 min after O. Fatty acids like AA, on the other hand, and its enzymatic byproducts tend to have longer half-lives. Assuming you forgot to take your supplements that day, the only inhibitors that might work after an orgasm are COX/LOX/CYP450 enzyme inhibitors (taken before sickness starts).

  Things are starting to pick-up at work. I am preparing to write a paper and apply for a research fellowship (unrelated to POIS). So I may not reply to the forum as often as I would like. Please forgive me if I do not reply in a timely manner.

1.   Contact with attractive women affects the release of cortisol in men (2010)
2.   Specificity of the neuroendocrine response to orgasm during sexual arousal in men (2003)
« Last Edit: July 28, 2017, 10:55:13 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 #28 on: July 28, 2017, 11:30:31 AM »
Hi Nanna,

Thanks for the link to that article on AA and EPA/DHA, it is very informative.  I have known for years that omega-3 acids were beneficial for my emotional state.  As mentioned, I do not have cognitive symptoms, but have a lot of emotional symptoms.  In fact, I use to have a high anxiety level and unstable emotions, even out of POIS, and that would skyrocket in POIS.   So, even before developing my pre-pack, I was using omega-3 to reduce anxiety, mood swings, irritability, and all of my emotional symptoms.    In the article you suggested, there is an interesting note about taking some gamma linolenic acid, or GLA, when you take DHA.  I was glad to see that hemp, which I add to my smoothies and cereals in the form of hemp heart, and spirulina, that I take on its own ( it ruins the taste of my smoothies!), are good sources of GLA.

LOL, about the 2010 study on cortisol, in order to lower cortisol and stress, I will have to hang out more with my tennis buddies and stay away from my spouse.... ;)    Unless I compensate with meditation, yoga and tai chi, like I have been doing :)

I totally agree with you, that inhibitors are more effective if taken before the triggering event occurs.  It was the premise of my pre-pack strategy, and leads to good results for me.   Inhibitors acting downstream ( cox, lox, cyp450), as you noticed, can still show high efficiency if taken after release but before the symptoms appears.  In that since NSAIDS like celecoxib blocking COX2 , and a good 5-LOX inhibitor like boswellia could be a good "last minute combo" after release, before symptoms appear.


About AA, it seems that the presence of lipid peroxidation products seriously aggravate the negative effects of AA ( https://en.wikipedia.org/wiki/Arachidonic_acid#Dietary_arachidonic_acid_and_inflammation ).  This could be another good reason for the various antioxidants of my pre-pack to help lower my POIS symptoms severity.  For example, my "friend" curcumin is good at inhibiting lipid peroxidation ( https://www.researchgate.net/publication/15483898_Curcuminoids_as_Potent_Inhibitors_of_Lipid_Peroxidation ), as well as the EGCG found in my green tea extract ( https://www.ncbi.nlm.nih.gov/pubmed/20852116 ).  And I suppose that my other antioxidants sources, like rosemary essential oil, must have that property, too.    All together, they do a good teamwork, though.

I would like to add, for the benefit of all members, that it is never too late to take substances and products that helps reducing inflammation and the POIS inflammatory cascade.  Granted, they are more efficient when taken before, but taking them late will be better than not taking them.

I wish you good luck for your research fellowship application, Nanni.  I look forward to continue this enriching discussion with yourself and the other members. 


In the meantime, I may do some tests and add some vitamin B1 to my pre-pack or on a "as needed" basis.  Your explanation about B1 being a downregulator of the h1H receptors through PKC inhibition was very interesting, and seems to make it a good addition to my overall approach.  In addition, it helps reduce histamine levels, which is good in my case, and in POIS cases in general, I think.   I have tolerance issues with methylfolate, but not with methylcobalamine, neither with thiamine, so it's not complicated for me to add some B1.





« Last Edit: August 02, 2017, 09:27:53 AM by Quantum »
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Quantum

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Re: POIS cure: theory & supplement stack
« Reply #29 on: July 28, 2017, 12:31:45 PM »
From month to month, I oscillate between adding supplements to my stacks and simplify them. I am in the adding mode right now, and probably will go into a subtraction mode in 3 months. lol

Lol, romies....hehe.... In my initial phase, I have done a huge number of tests.  After that, I just stayed there, didn't move, keep the course, everything seems ok.... like " i had enough up and downs and side effects, I want to keep it simple and calm".

Like I wrote, I may add a little vitamine B1, because I already know I tolerate it well. 

But I still have new ingredients/products I didn't try, even if I ordered them and have them here... like NADH, and Cat's claw.....   at some points, I was satisfied with my pre-pack, and didn't want to risk a bad reaction to an unknown product, like I had with methylfolate, even at low dose.   Anyway, I take at max 1/4 of the usual dose,  for years, when trying something new, as a tolerance test, and then I raise the dose sloooooowly :)
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 #30 on: August 01, 2017, 12:32:26 PM »
Hi All,
  I had been looking for a more economical methyl donor than alpha-GPC. So I recently purchased a tub of betaine (TMG) and tried it out for a few days. It seems to work well. I am still symptom free replacing alpha-GPC with TMG, and TMG is dirt cheap.

  So I updated the original (1st) post to use daily TMG supplementation:
tri-methylglycine, betaine (1.5g) [methyl group donor](https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_5_a_it?ie=UTF8&qid=1501608656&sr=8-5&keywords=betaine&th=1)
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 #31 on: August 01, 2017, 04:19:00 PM »
Hi All,
  I had been looking for a more economical methyl donor than alpha-GPC. So I recently purchased a tub of betaine (TMG) and tried it out for a few days. It seems to work well. I am still symptom free replacing alpha-GPC with TMG, and TMG is dirt cheap.

  So I updated the original (1st) post to use daily TMG supplementation:
tri-methylglycine, betaine (1.5g) [methyl group donor](https://www.amazon.com/Nutricost-Betaine-Anhydrous-Trimethylglycine-Powder/dp/B01BCQ3RLE/ref=sr_1_5_a_it?ie=UTF8&qid=1501608656&sr=8-5&keywords=betaine&th=1)

That's interesting. I've been taking TMG daily for years, and yet I still feel the difference when I take alpha-GPC or CDP-Choline.

My daily AM pack has one methyl guard capsule in it, and each capsule has
Vitamin B6 (as Pyridoxal 5'-Phosphate) 6.6 mg.
Folate (as L-5-Methyltetrahydrofolate from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt) 0.4 mg.
Vitamin B12 (as Methylcobalamin) 0.4 mg.
Betaine Anhydrous (Trimethylglycine) 0.6 g.

romies

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Re: POIS cure: theory & supplement stack
« Reply #32 on: August 01, 2017, 04:20:32 PM »
nanna1,

What is your C667T and A1298C status?

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #33 on: August 01, 2017, 05:25:27 PM »
Hi Romies,

I agree that alpha-GPC and CDP are higher quality sources than TMG because they both supply phosphorus at the right location and can be used to make phosphatidylcholine. I am just trying to conserve money and pure phosphatidylcholine does not seem to absorb so well from the gut. But in general, I think alpha-GPC is the best source.

I haven't done genetic testing, so I don't officially know the status of my MTHFR genes. However, in the Homocysteine Cycle, the betaine path (of homocysteine to methionine) bypasses the MTHFR (and B12) dependent folate cycle. I think that as long as I'm supplementing with SAM-e and a methyl donor (choline or betaine), the C667T and A1298C status shouldn't matter [1]. I could be wrong though.

1. Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets. (2016)
« Last Edit: August 01, 2017, 09:19:41 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 #34 on: August 02, 2017, 12:59:13 PM »
I haven't done genetic testing, so I don't officially know the status of my MTHFR genes. However, in the Homocysteine Cycle, the betaine path (of homocysteine to methionine) bypasses the MTHFR (and B12) dependent folate cycle. I think that as long as I'm supplementing with SAM-e and a methyl donor (choline or betaine), the C667T and A1298C status shouldn't matter [1]. I could be wrong though.

1. Betaine is as effective as folate at re-synthesizing methionine for protein synthesis during moderate methionine deficiency in piglets. (2016)

I agree with you that Betaine is an effective methyl donor, and it generates 1 SAMe and 2 methyl-folate molecule when it gets converted into glycine.

However, depending on your A1298C status, you might have excess SAMe in circulation from supplementation. Normally SAMe is an allosteric inhibitor of MTHFR., However, people with A1298C mutation reportedly don't have this negative feedback, as discussed in the first paper on A1298C
http://dx.doi.org/10.1006/mgme.1998.2714

Too high the serum SAMe can cause manic episodes for some people. But it may or may not be a risk for you.

I am personally A1298C homozygous, so I have been careful with SAMe, and I use a low-dose methylfolate supplement every day.

The cancer risk for methylfolate really kicks in when one takes *prolonged* doses 250% above RDA. The RDA is about 400 mcg/day. Folate deficiency and excess are both associated with colorectal cancer risk, and there are many journal pubs on this, a relative good review can be found: https://examine.com/supplements/folic-acid/

Moreever, depending on your C677T and A1298C status, your optimal folate intake level may be higher. That is why I asked you earlier.

romies

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Re: POIS cure: theory & supplement stack
« Reply #35 on: August 02, 2017, 01:10:45 PM »
I agree that alpha-GPC and CDP are higher quality sources than TMG because they both supply phosphorus at the right location and can be used to make phosphatidylcholine. I am just trying to conserve money and pure phosphatidylcholine does not seem to absorb so well from the gut. But in general, I think alpha-GPC is the best source.

Sorry to hear that Cholines are a lot more expensive than TMG in your country. I had no idea, since they are priced similarly in my country.

alpha-GPC and CDP are similar in raising brain levels of choline, but
   ? GPC is 40% choline by weight, while CDP is 18-19% ? a pretty major difference
   ? CDP is essentially a uridine supplement as well as a choline supplement
   ? CDP has been shown to restore dopamine receptor densities in aged rodents
                  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1908237/
   ? CDP was shown to improve symptoms of Parkinson?s, presumably through increasing dopamine receptor density
                  https://www.ncbi.nlm.nih.gov/pubmed/1863939
   ? Alpha-GPC has been studied and shown to enhance GH release.
                  https://www.ncbi.nlm.nih.gov/pubmed/22673596

nanna1

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Re: POIS cure: theory & supplement stack
« Reply #36 on: August 02, 2017, 08:47:17 PM »
Thanks Romies for sharing that information on the MTHFR variants. I was not aware of the complexity with the variants. I knew that some were more efficient than others. But this discussion makes me curious about my gene variants. I still have a bottle of Metafolin that I have had for almost a year. As you can tell I don't take it very often anymore. It would be nice to know what my optimum dosage should be. How do you get the genetic test done? Do you go to a doctor?

I guess I lucked out with SAM-e. I have not had any negative side effects, except for one time when I took it close to bed time. That night I had poor sleep and woke up with a headache that lasted five or six hours. But I learned my lesson.  :D

I agree alpha-GPC and CDP have a diverse array of benefits. I didn't know that a-GPC enhanced GH, but that makes sense since it increases acetylcholine. I may start back sup with a-GPC before my workouts! That effect of a-GPC on dopamine receptors is great for my mood. I thought about pairing my betaine dosage with equal-molar uridine monophosphate to try and mimic the cognitive effects CDP. Don't know if that will work since betaine is not apart of the CDP-choline cycle, but it may be worth a try. Thanks Romies
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 #37 on: August 07, 2017, 09:16:35 AM »
Thanks Romies for sharing that information on the MTHFR variants. I was not aware of the complexity with the variants. I knew that some were more efficient than others. But this discussion makes me curious about my gene variants. I still have a bottle of Metafolin that I have had for almost a year. As you can tell I don't take it very often anymore. It would be nice to know what my optimum dosage should be. How do you get the genetic test done? Do you go to a doctor?

I did my test with 23andme.com . I did not go through my doctor, because most of the primary physicians in my town are not well versed in genetic counselling

demografx

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Re: POIS cure: theory & supplement stack
« Reply #38 on: August 07, 2017, 02:49:33 PM »
Thanks, romies!
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

romies

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Re: POIS cure: theory & supplement stack
« Reply #39 on: August 10, 2017, 09:56:57 AM »
Regarding the genetic testing, I get the raw data from 23andme after testing, and then use http://geneticgenie.org/ (free) and https://promethease.com ($5) to run analysis. The MTHFR variants are mostly covered by geneticgene.

Edit: Corrected typos in the url. Hat tip nanna1.
« Last Edit: August 12, 2017, 12:42:52 PM by romies »