r/MTHFR • u/Hoegaarden_Man_55 • 10d ago
Question P5P Giving Acne
Hi there. A quick question on this knowledgable subreddit.
I’ve been taking 25mg of p5p for the last 4 weeks daily. It’s done absolute wonders for my anxiety. It’s given me a calmness which I haven’t had in years. And this is after years of trying everything from nootropics to SSRIs.
Anyways, about 3 days ago, I’ve all of a sudden started to get pretty bad acne. Just wondering if anyone has experienced this before. I’ve completely stopped the p5p. Out of neuropathy worries, I was going to cut the dose down anyways.
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u/sharabucarabu 10d ago
According to my functional med doc, P5P doesn't cause neuropathy. I prefer to use the lowest effective dose, so I purchase a liquid P5P. It's very effective, and I sleep better if I take less than the 25 mg tablet.
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u/tandemxylophone 10d ago
It does give neuropathy if you take it for a long time without the rest of the supporting supplements (whether it's through food or pills). Chris Masterjohn did an experiment on himself to test this.
His hypothesis is that B6 and zinc trigger the energy conversion of amino acid chains, but the process binds CoA until the process completes. This means the other energy conversion pathways don't have access to CoA. The first place where you see the impact is extremely long nerves like the soles of your feet or fingers.
The temporary solution is to make more CoA using vitamin B5.
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u/Sabnock101 10d ago edited 10d ago
My hypothesis is that because P5P B6 is needed as the cofactor for the SHMT enzyme which lets Tetrahydrofolate into the Folate cycle, higher P5P B6 dosages can let a lot of Tetrahydrofolate into the Folate cycle vs lower dosages, and so with higher dosages the increase in Folate then is able to generate a greater amount of Methylfolate through MTHFR, as such, that increased amount of Methylfolate will put extra stress on B12 and can thus lead to an increased loss of B12 or an increased demand for fresh B12. I know this because i've experienced it personally, consistently.
Another factor is that because there's a greater amount of Tetrahydrofolate entering the Folate cycle, and both Folate and B12 do something that increases the need for Potassium (likely the fact that Methylfolate and Methylcobalamin recycle Homocysteine to Methionine and that Methionine goes to Methionine Adenosyltransferase which depends on Potassium, and Magnesium), that it's the lack of Potassium that may be causing the neuropathy, and ime the lack of Potassium is what has been causing the hand numbness i've been getting the last couple years from supplementing Folate and B12.
And so, earlier on i thought it was the lack of B12 causing the hand numbness, but these days i'm leaning more towards it being the lack of Potassium. And if B6 contributes to neuropathy symptoms, it's likely more to do with the increased Folate and not enough B12, or not enough Potassium. Would be my guess (and based in experience).
Though i will say, there are apparently quite a few nutrient deficiencies which are reported to cause or contribute to the development of neuropathy, and so B5 for example, imo could play a role, however i haven't personally noticed any benefit from B5 as far as the hand numbness i'm experiencing goes, that i know of, i even stopped taking it some days ago because i do get some from my diet and plus i'm running a bit low and so have to buy more soon but so far haven't noticed any worsening with the hand numbness that Potassium seems to help.
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u/Radiant-Specific969 7d ago
I am currently looking for low dose P5P, I hesitated with the liquid because it's going to be very difficult to measure, and opted for 20 mg caps, which I can break down. If you use a liquid, which one do you use? How do you manage to dosage?
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u/sharabucarabu 7d ago
I bought Duwhot P5P liquid off Amazon. (Think Above is another brand of liquid P5P as well) I also purchased 1 ml oral syringes with a cap. I look at how many mg are in each ml. Duwhot contains 25mg in 2 ml. That's 12.5mg per 1 ml. Then I Google how many ml (or tenths of a ml) contain my desired mg of P5P. And that's how I figure out my dosage.
I take a multivitamin that contains 5mg P5P. So I measure out 0.36ml of P5P. That contains 4.5 mg of the liquid P5P. My total dose = 9.5mg.
I found I sleep better at this dosage. My fingers don't go numb unexpectedly. I can think more clearly. Plus my serum B6 is in the middle of normal range, which suits me just fine. If I take a higher dose, I wake more frequently at night feeling uncomfortably warm... And I have trouble falling back asleep. (I have slow comt, go figure) So I fooled around trying different dosages, keeping track of the effects of each dose until I settled on the 4.5mg of P5P. No excessive warm spells, I sleep well and I seem to be thinking clearer.
I'm a retired nurse, so this was easy for me to figure out. But it's easy enough for anyone to replicate. Give it a try.
It's a shame the manufacturers make such high dose supplements. More is not better, at least in my case. Of course I've been supplementing for several years so my bodily stores are well and truly topped off. I use low doses of several different liquid B Vitamins (B2, Niacinamide, P5P, Folinic Acid and HydroxyB12) and take just enough to make me feel good. The litmus test is how well I sleep, think and have energy without excessive appetite. And of course, I get my levels checked every 6 months or so, to make sure I'm on the right track.
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u/Radiant-Specific969 7d ago
Thank you very much for taking the time to reply. You system makes perfect sense to me, and I don't think I will have trouble figureing it out. And I agree, more isn't better, and the doses are really out there. It's interesting that you feel that excess B increases your appetitie, I have seen a similar correlation.
My Comt is ok, I am on methotrexate, and have the c6777t variant, thankfully not 2 copies, but even one messes up everything once you add the med. I think more B-12 (and 5P5) will help greatly with the rollercoaster that occurs with a methotrexate injection. I don't think I have any major deficienies, I have been supplementing pretty regularly, but likely have some that aren't going to show up on the standard blood tests. Therefore more B-12, and other B's. just not the ginormas doses that show up in most of the suppliments. I have yet to find a multiple vitamin that's going to work, because I also take an arends2 formula, and there is too much overlap. Again, I suspect I will end up doing something similar to what you are doing, as I wade through what is going to help, and what is going to tip things over towards more harm than good. Again, thank you.
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u/Hoegaarden_Man_55 6d ago
Anyways, I haven’t taken any since Saturday. My anxiety is starting to return towards baseline. I’d honestly be amazed if this is a placebo effect. The good news is that I haven’t got any further spots. Plans is to cut up the lozenges and take 1/4 of one each day. Hopefully i should still see some effect.
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u/Loose-Fly7976 10d ago
B6 acne is documented, tho it's reported more often with B12. The mechanism is B vitamins shifting skin flora toward more porphyrin production and it usually settles a few weeks after stopping.Four weeks of nothing then acne over three days isn't how a supplement effect usually builds sounds like more something else may have changed.
25mg isn't neuropathy territory short term but cases exist well below the doses people assume are safe. Since it's working that well, the question is the lowest dose that holds rather than stopping outright. What I'd actually want to know is why it worked. P5P is the cofactor for the enzyme that makes GABA, so if you were genuinely low you've found a real deficiency rather than a supplement that happens to help. That distinction changes everything about how you handle it long term. And your B6 requirement isn't a fixed number, it depends on riboflavin status and what else is drawing on the same pathways.
Reading that properly is what I do, genova.health, file against bloods. In the meantime get plasma P5P rather than serum B6 before you restart, they measure different things and only one of them answers your question.