Clues to Mechanisms of Excessive-Pyridoxine-Induced Peripheral Neuropathy

Keep in mind that I haven't looked at these articles, and I'm not suggesting that anyone would want to try to protect against peripheral neuropathy due to excessive pyridoxine dosages. But understanding the mechanisms helps one understand vitamin B6 metabolism. The peripheral neuropathy isn't just going to suddenly appear at 201 mg/d and be absent at 200 mg/d. The same mechanisms are probably at work at the lower doses, but the same mechanism (activation of some enzyme) could produce a protective effect at one dose of pyridoxine and toxicity at another, for example, depending on any number of factors. Or the "toxic mechanism" could just work at a low level at lower doses. Here's an article showing that glutamate at 0.5 g/kg bw/d (by intraperitoneal infusion) protected against peripheral neuropathy caused by pyridoxine (vitamin B6) [Arkaravichien et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/12909271)]. Arkaravichien et al. (2003) also found that 1 mg/kg bw/d, i.p., worsened the neuropathy. Kaneda et al. (1997) [Kaneda et al., 1997: (http://www.ncbi.nlm.nih.gov/pubmed/9098696)], "in contrast," found that pyridoxine protected against glutamate neurotoxicity in cultured neurons. That's not a fair comparison, for various reasons. But pyridoxine has crazy and complex effects. One article I read recently discussed the fact that coenzymated pyridoxine is a cofactor for over 100 different enzymes.