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Comment · Fri, November 17, 2023 · ND Owner

Unable to tolerate P5P

Original post in this thread

deanr11 · 7 points

I am sensitive to neuropathy from supplements but recently started taking P5P at the recommendation of my doctor. I found the effects of P5P beneficial — help with focusing and attentiveness — but experienced neuropathy at doses as low as 7 mg.

Does anyone know why I might be experiencing this and how I can experience the benefits of B6 without the side effects? I know it is an important co-factor in dopamine production.

I have seen Lucas Aoun (recent guest on ND’s podcast) discuss how he doesn’t recommend supplanting B6 and has had clients who experience neuropathy with P5P even though it is thought to be well tolerated. Link to that here in comments

What they were answering

deanr11 · 1 points

I’m currently using Source Naturals 25mg because it’s a tablet and easier to split into a smaller dose

u/MisterYouAreSoDumb · ND Owner

So the mechanism behind high B6 levels causing peripheral neuropathy are a reduction in GABA, due to inhibition of PDXK, which results in disrupted GABA signaling. This should only happen with pyridoxine, though. This is because l-glutamic acid decarboxylase is a pyridoxal 5′-phosphate-dependent enzyme responsible for the formation of GABA, and taking too much pyridoxine can inhibit P5P formation, which then lowers GABA. I'd have to test Source Naturals product to see if it is really pure P5P. You could supplement GABA to help counteract this effect. There is evidence that not getting enough protein in your diet plays a role in whether you get toxicity from B6 supplementation.

Pyridoxine \(Vitamin B6\) Neurotoxicity: Enhancement by Protein-deficient Diet

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