There is good agreement concerning average requirements and reference intakes for vitamin B 6 but less agreement over safe upper levels from supplements. High-dose supplements cause sensory nerve damage. Supplements of vitamin B 6 have been advocated for treatment of the premenstrual syndrome, with little evidence of efficacy. There are plausible mechanisms for an antidepressant action and protection against steroid hormone-dependent cancers but no evidence from clinical trials. Pyridoxamine reduces the glycation of proteins and so could be beneficial in preventing the adverse effects of poor glycemic control in diabetes. There are plausible mechanisms for an antihypertensive action but only suggestive evidence from small intervention trials. There is no evidence that supplements of vitamin B 6 have any beneficial effect in hyperhomocysteinemia. There is neither a plausible mechanism nor any evidence from controlled trials for any effect of supplements of vitamin B 6 in preventing a decline in cognitive function with aging, amelioration of dementia or autism, or improvement of the carpal tunnel syndrome.Average adult requirements for vitamin B 6 are of the order of 1.3 to 1.4 mg/d, and reference intakes for adults are between 1.5 to 1.7 mg/d, with a slightly higher reference intake for people aged more than 65 years. These requirements and reference intakes have been based on normalization of tryptophan metabolism, optimization of plasma transaminase activity, and the plasma concentration of pyridoxal phosphate or total vitamin B 6 . 1-4 A number of dietary surveys have shown that a significant number of people in developed countries have inadequate intakes of vitamin B 6 , 5 and in various studies, 10% to 20% of healthy people show signs of biochemical inadequacy or marginal deficiency 6 by one or another of the indices of nutritional status.The main form of vitamin B 6 used in supplements is pyridoxine; as shown in Figure 1, this is readily phosphorylated and oxidized to the metabolically active coenzyme pyridoxal phosphate. Pyridoxal phosphate is involved in 3 main areas of metabolism: as the coenzyme for many reactions in amino acid metabolism, where it is the aldehyde group that is important 7 ; as the coenzyme for glycogen phosphorylase in liver and muscle, where it is the phosphate group that is important 8 ; and in attenuating the nuclear actions of steroid hormones, where it is again the aldehyde group that is important. 9 Pyridoxamine phosphate is formed in some reactions and is readily interconvertible with pyridoxal phosphate.In a small number of very rare genetic conditions, a mutation in a pyridoxal phosphate-dependent enzyme results in a very low affinity of the enzyme for its coenzyme, and the affected enzyme only has significant activity when the tissue concentration of pyridoxal phosphate is very much higher than normal. For these conditions, supplements of vitamin B 6 of between 200 and 1000 mg/d are required throughout life. [10][11][12] The antituberculosis drug isoniazid (iso-nicotinic acid ...