The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. (October 2017)

• Record Type: Journal Article
• Authors: Vrolijk, Misha F.; Opperhuizen, Antoon; Jansen, Eugène H.J.M.; Hageman, Geja J.; Bast, Aalt; Haenen, Guido R.M.M.
• Is Part Of: Toxicology in vitro. Volume 44(2017)
• Page Start: 206
• Page End: 212
• Publication Date: 2017-10
• Subjects: Vitamin B6 -- Neuropathy -- Pyridoxine -- Supplements -- Neurotoxic; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2017.07.009
• Languages: English
• ISSNs: 0887-2333

Abstract

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 24 h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24 h 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. Highlights: Pyridoxine is the toxic form of vitamin B6. Neuronal cells are sensitive to the toxic effects of pyridoxine. The inactive form PN competitively inhibits the active PLP. Symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.