The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function
The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function
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DOI：
10.1016/j.tiv.2017.07.009
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发表时间：
2017-10-01
影响因子：
3.2
通讯作者：
Haenen, Guido R. M. M.
中科院分区：
文献类型：
--
作者：
Vrolijk, Misha F.;Opperhuizen, Antoon;Haenen, Guido R. M. M.
维生素B6是一种水溶性维生素，在氨基酸、碳水化合物和脂肪代谢的许多反应中作为辅酶发挥作用。自2014年以来，共报告了50例因补充维生素B6引起的感觉神经元性疼痛。到目前为止，这种毒性的机制仍然是个谜，各种B6维生素对这种毒性的贡献在很大程度上还不清楚。在本研究中，测试了不同形式的维生素B6对SHSY5Y和Caco-2细胞的神经毒性。细胞暴露于吡哆醇、吡哆胺、吡哆醛、5-磷酸吡哆醛或5-磷酸吡哆胺作用24 h后，用四甲基偶氮唑盐比色法测定细胞存活率。染毒24 h后检测Bax和caspase-8的表达。实验还检测了维生素对两种5-磷酸吡哆醛依赖酶的影响。吡哆醇以浓度依赖的方式诱导SHSY5Y细胞死亡。其他维生素对细胞活力没有影响。吡哆醇显著增加Bax和caspase-8的表达。此外，两种5-磷酸吡哆醛依赖的酶都被吡哆醇抑制。综上所述，本研究表明，服用较高剂量的维生素B6补充剂后观察到的神经病变是由于吡哆醇引起的。非活性形式的吡哆醇竞争性地抑制活性的吡哆醛-5‘-磷酸。因此，补充维生素B6的症状与缺乏维生素B6的症状相似。
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-5phosphate 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.