Some time ago, I mentioned that the form in which we take vitamin B6 is important. I think I linked to this paper:
Toxicol In Vitro . 2017 Oct;44:206-212.
doi: 10.1016/j.tiv.2017.07.009. Epub 2017 Jul 14.
The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function
Misha F Vrolijk 1 , Antoon Opperhuizen 2 , Eugène H J M Jansen 3 , Geja J Hageman 4 , Aalt Bast 4 , Guido R M M Haenen 4
• PMID: 28716455
• DOI: 10.1016/j.tiv.2017.07.009
Abstract
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
Keywords: Neuropathy; Neurotoxic; Pyridoxine; Supplements; Vitamin B6.
Full paper is, unfortunately, behind a paywall:
pubmed.ncbi.nlm.nih.gov/287...
In the paper, they define mega doses as > 50. And the low doses at which negative effects have been noticed being as little as 2. The conclusion of the paper says:
In conclusion, the present study strongly indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to the vitamer that is used in the supplements, namely pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-phosphate. As a consequence, the paradox arises that the symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency. Vitamin B6 supplements are used by a large number of people. The safety of vitamin B6 is debated and recently EFSA has lowered the upper limit for vitamin B6. The question is whether lowering the safe dose for vitamin B6 is the solution. Remarkably, even at relatively low dose, vitamin B6 supplementation has given rise to complaints. Our study indicates that the toxicity of vitamin B6 is not only determined by the dose, but by the vitamer in which it is taken. Perhaps it might be better to replace pyridoxine by pyridoxal or pyridoxal-phosphate as vitamin B6 supplements, which are much less toxic. In this way, the vitamin B6 paradox may potentially be prevented.
I'd rather play safe and avoid any pyridoxine in supplements.