Pyridoxine

Uses

Pyridoxine is used to prevent adverse nervous system reactions to isoniazid [ , ]. Adherence to therapy is improved by prescribing combined tablets containing 20 mg of pyridoxine per 100 mg of isoniazid.

Megadoses of pyridoxine are commonly used to treat homocystinuria, cystathioninuria, and primary oxalosis type I [ , ]. In some diseases pyridoxine is used empirically, including rheumatic diseases, degenerative joint diseases, carpal tunnel syndrome, Chinese restaurant syndrome, and premenstrual syndrome. A rare form of neonatal seizures, reported as early as 1954, seems to respond only to large doses of pyridoxine [ , ]. Occasionally, the condition can appear up to 2 years after birth. Affected patients can have abrupt seizure cessation and dramatic improvement in the electroencephalogram after receiving an intravenous dose of pyridoxine 50–100 mg. The mechanism of this rare condition is unclear. It has been suggested that in these infants there is a shift in the balance of glutamate and GABA in the central nervous system; giving pyridoxine increases the co-enzyme pool, offsetting the adverse kinetics that result from altered glutamate decarboxylase binding. One adverse consequence of the large dose of pyridoxine required is a diffuse inhibitory state, with effects ranging from excessive drowsiness to coma and electrocerebral silence. Resuscitation equipment should be on hand if this treatment is used.

Extremely high doses of pyridoxine, even up to 6000 mg/day, have also sometimes been used therapeutically. While few problems arise from controlled application of high doses of pyridoxine under medical supervision, self-medication in doses exceeding 300–500 mg/day can lead to adverse effects, especially when continued over a long period of time. Many patients have self-medicated with more than 2000 mg/day for long periods of time.

In many countries, pyridoxine is a component of “vitamin B complex” products, administered orally or parenterally as “tonics,” commonly because of their supposedly beneficial effects on the nervous system. Pyridoxine is marketed for stress in general, for depression associated with premenstrual syndrome and oral contraceptives, and for carpal tunnel syndrome, although it is doubtful that it has more than a placebo effect.

Under the headline “Still time for rational debate about vitamin B6” the controversial debate on the safety of pyridoxine has been revived in a Lancet editorial, which refers to the attempts of the UK Government’s Committee on Toxicity to find the safe level of daily consumption of pyridoxine [ ]. In July 1997 the committee recommended that the sale of pyridoxine in, for instance, health-food shops would be restricted to doses of 10 mg/day. Doses between 10 and 50 mg would be restricted to sale at pharmacies; and doses of 50 mg and above would be available only on prescription. Contrary to these UK recommendations the Committee of the US National Academy of Science concluded that there were no convincing reports of adverse events at doses of up to 200 mg/day. Paying attention to the fact that recommendations tend to be more cautious than might seem necessary from the available evidence, the US experts halved the 200 mg/day dose to define their limit as 100 mg/day. The author of the editorial found fault with the fact that the US experts have based their recommendations on the slimmest of evidence.

In a letter to the editor, Beckett [ ] pointed out that daily doses of 200 mg or less have been taken by millions of people worldwide for several decades without evident toxicity and that testimonials from clinicians expert in the use of pyridoxine have attested to its safety in these doses [ ]. Referring to the editorial, the author of the study in question stated that their study referred to 172 women with raised blood concentrations of pyridoxine that reverted to normal within 4 days of stopping pyridoxine, and was not a “self-recall series.” In a recent follow-up of these women who had raised blood concentrations, compared with controls from the same practice who had had a blood test in 1985–86 and whose record showed that they were not taking pyridoxine or multivitamins at that time or since, 16 of 50 respondents had subsequently had autoimmune disease, compared with one of the 38 controls. The autoimmune diseases included thyroid disease (n = 5), rheumatoid arthritis (n = 3), diabetes (n = 2), Sjögren’s syndrome (n = 2), primary biliary cirrhosis (n = 1), polymyalgia rheumatica (n = 1), and polyarteritis nodosa (n = 1). In the controls there was one case of diabetes.

In another letter to the editor [ ] it was mentioned that the suspicion of partiality about the Committee on Toxicity becomes more plausible when one considers the issue of homocysteine. This intermediate metabolite may well turn out to be of greater importance as a risk factor for cardiovascular disease than cholesterol and blood pressure. Raised homocysteine concentrations appear to be accessible to treatment with pyridoxine (100 mg/day) together with vitamin B ₁₂ and folic acid [ ]. Furthermore, the statement that there is no good evidence for the efficacy of pyridoxine in any disease, apart from depression, was criticized, because this ignores important studies in autism, pregnancy outcome, asthma, and sickle-cell anemia [ ].

In a systematic review on the efficacy of pyridoxine in the treatment of premenstrual syndrome, adverse reactions were reported in 63 patients (6.7%) (see Table 1 ) [ ]. In another study of 940 women one had a neuropathy associated with pyridoxine toxicity [ ].