Vrolijk · Toxicology in vitro : an international journal published in association with BIBRA 2017 · in vitro cell culture study · n=?

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

Cited 157 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

In vitro cell line and enzyme assay study (bench research)

PubMed 28716455 · doi:10.1016/j.tiv.2017.07.009 · record verified 2026-08-29

What was done

Human neuroblastoma (SHSY5Y) and intestinal epithelial (CaCo-2) cells were exposed for 24 hours to five distinct vitamin B6 vitamers: pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate, or pyridoxamine-5-phosphate. Following exposure, cell viability was measured using the MTT assay, and expression of apoptotic markers Bax and caspase-8 was quantified. The effects of the vitamers on the activity of two pyridoxal-5-phosphate-dependent enzymes were also evaluated.

What was found

The abstract reports no exact numerical values, concentrations, or effect sizes. It states that pyridoxine induced concentration-dependent cell death in SHSY5Y cells, whereas the other vitamers did not affect cell viability. Pyridoxine significantly increased Bax and caspase-8 expression and inhibited both pyridoxal-5-phosphate-dependent enzymes.

Why it matters

This study proposes a mechanistic basis for peripheral neuropathy caused by high-dose vitamin B6 supplementation, suggesting that inactive pyridoxine competitively inhibits the active coenzyme pyridoxal-5'-phosphate to cause functional B6 deficiency.

Limits

All experiments were conducted in vitro using immortalized cell lines (SHSY5Y and CaCo-2) and isolated enzyme assays, which cannot replicate human pharmacokinetics, metabolism, or blood-nerve barrier dynamics. The abstract does not report specific vitamer concentrations, effect magnitudes, or statistical parameters.

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