The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function

Toxicol In Vitro. 2017 Oct:44:206-212. doi: 10.1016/j.tiv.2017.07.009. Epub 2017 Jul 14.


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.

MeSH terms

  • Alanine Transaminase / metabolism
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dietary Supplements / toxicity*
  • Humans
  • Polyneuropathies / chemically induced
  • Pyridines / toxicity*
  • Tyrosine Decarboxylase / metabolism
  • Vitamin B 6 Deficiency
  • Vitamins / toxicity


  • Pyridines
  • Vitamins
  • Alanine Transaminase
  • Tyrosine Decarboxylase