Comment · Tue, September 12, 2023 · Nootropics Depot & Natrium Health
Is B6 toxicity actually something I need to be worried about?
Original post in this thread
Banjosolo69 · 18 points
I just started a B complex and I’m loving it but I’ve seen several people on here warn about the dangers of B6 toxicity. When I google it I only find evidence stating that only abnormally high doses will cause damage, and when you stop taking it it should go away. My current B complex contains 25mg Pyroxidine and 3.4mg Pyridoxal 5’-Phosphate. What are your personal experiences with this?
What they were answering
MisterYouAreSoDumb · 9 points
Only with high doses of pyroxidine in certain people. The Wikipedia page on B6 induced peripheral neuropathy needs to be updated. Wiki is really getting bad for validity of information lately. The study cited for the claim that it is a risk with P5P as well is from 1985... Plus, it doesn't actually say that. Many studies since then have elucidated the actual mechanism.
The observation that the phosphorylated derivative was not toxic also suggested that it was not a physical effect of the molecule on the cell membrane that produced cell injury. Several mechanisms might account for the correlation between ability to serve as active coenzyme and toxic effect. In high concentrations, pyridoxine compounds combine together or with a second unidentified intracellular constituent to inhibit the pyridoxal. This might involve the formation of a hydrazone or other molecule similar to that produced with isoniazid (McCormick and Snell, 1959; McCormick et al., 1960; McCormick and Snell, 1961). These derivatives inhibit pyridoxal kinase (ATP:pyridoxal 5-phosphotransferase, EC 2.7.1.35) that catalyzes the production of the phosphorylated coe…
u/MisterYouAreSoDumb · Nootropics Depot & Natrium Health
They even give P5P to people experiencing peripheral neuropathy from high pyridoxine supplementation, and it treats them! That's because peripheral neuropathy from high doses of pyridoxine manifests as B6 deficiency, because it is about pyridoxine inhibiting P5P in the body.
96% of case reports of peripheral neuropathy were from pyridoxine supplementation.
Hence, not only the dose, but also the vitamer present in the vitamin B6 supplements is important for the development of such adverse health effects. This is also presented by the data from Lareb, showing that more than 96 % of the reports is due to the use of PN in the supplements. The fact that the vast majority of the available vitamin B6 supplements contain PN must be taken into consideration here.
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
In that study, they only saw toxicity from pyridoxine in the animals fed low protein diets. Moreover, they injected large doses of P5P and did NOT see any toxicity at all, even in the low protein diet group. They discuss the factor of protein binding on the toxicity of pyridoxine as well. There is also evidence that pyridoxine toxicity to sensory neurons is due to a lowering of P5P centrally, likely through inhibition of PDXK, which results in disrupted GABA signaling. This is likely because l-glutamic acid decarboxylase is a pyridoxal 5′-phosphate-dependent enzyme responsible for the formation of GABA. Taking too much pyridoxine can inhibit P5P formation, which then goes to lower GABA concentrations, causing glutamate toxicity. Again, taking P5P solves this. This is the prevailing theory right now.
I copied some of this from other comments, but this gives you a good idea of the situation. What I want to see is someone that has gotten peripheral neuropathy from high dose pyridoxine being given a GABA supplement. If the mechanism is as the prevailing theory suggests, supplementing GABA direct should fix it. My neighbor is a physician treating peripheral neuropathy patients. I will see if he can get some of them to test the GABA supplement theory.