Pharmacological Uses and Toxicity of Vitamin B6 Supplements

Supplements of vitamin B6 ranging from 25 to 500 mg/day, and sometimes higher, have been recommended for treatment of a variety of conditions in which there is an underlying physiological or biochemical mechanism to justify the use of supplements, although in most cases there is little evidence of efficacy. Such conditions include postnatal depression, depression and other side effects associated with oral contraceptives, hyperemesis of pregnancy, and the premenstrual syndrome.

Supplements have also been used empirically, with little or no rational basis, and little or no evidence of efficacy, in the treatment of a variety of conditions, including acute alcohol intoxication, atopic dermatitis, autism, carpal tunnel syndrome, dental caries, diabetic neuropathy, Down's syndrome, Huntington's chorea, schizophrenia, and steroid-dependent asthma.

Doses of 50-200 mg per day have an antiemetic effect, and the vitamin is widely used, alone or in conjunction with other antiemetics, to minimize the nausea associated with radiotherapy and to treat pregnancy sickness. There is no evidence that vitamin B6 has any beneficial effect in pregnancy sickness, nor that women who suffer from morning sickness have lower vitamin B6 nutritional status than other pregnant women.

Vitamin B6 and the Side Effects of Oral Contraceptives

Although oestrogens do not cause vitamin B6 deficiency, the administration of vitamin B6 supplements has beneficial effects on some of the side effects of both administered and endogenous oestrogens. The supplements act in two main areas: in normalizing glucose tolerance and as an antidepressant.

Impairment of glucose tolerance is common in pregnancy and may indeed be severe enough to be classified as gestational diabetes mellitus, which generally resolves at parturition, although in some subjects it may persist. High-estrogen oral contraceptives may also cause impaired glucose tolerance. This seems to be the result of increased tissue and blood concentrations of xanthurenic acid, because of the inhibition of kynureninase by estrogen metabolites. Xanthurenic acid forms a complex with insulin which has little or no hormonal activity. Vitamin B6 supplements may have a beneficial effect by activating apokynureninase or kynureni-nase that has been inactivated by undergoing transamination.

One of the relatively common side effects of oestrogenic oral contraceptives is depression, affecting about 6% of women in some studies. This frequently responds well to the administration of relatively large amounts of vitamin B6 (generally in excess of 40 mg per day). Postnatal depression also responds to similar supplements in some studies.

Again, this does not seem to be due to correction of vitamin B6 deficiency, but rather to a direct effect of pyridoxal phosphate on the metabolism of tryp-tophan. High concentrations of pyridoxal phosphate attenuate the response to glucocorticoid hormones; tryptophan dioxygenase is a glucocorticoid-induced enzyme, and thus its synthesis and activity will be reduced by high intakes of vitamin B6. This reduces the oxidative metabolism of tryptophan and increases the amount available for synthesis of 5-hydroxytryptamine in the brain.

Vitamin B6 in the Premenstrual Syndrome

The studies showing a beneficial action of vitamin B6 in overcoming depression associated with oral contraceptives have led to the use of the vitamin in depression and other pathology associated with endogenous estrogens in the premenstrual syndrome. There is no evidence of poorer vitamin B6 nutritional status in women who suffer from the premenstrual syndrome.

There are few well-controlled studies of the effects of vitamin B6 in premenstrual syndrome. In general, those that have been properly controlled report little benefit from doses between 50 and 200 mg per day compared with placebo, although some studies do claim a beneficial effect. Interestingly, meta-analysis of controlled crossover trials shows that whichever treatment is used second, active vitamin or placebo, is (marginally) more effective. There is no obvious explanation for this observation.

Despite the lack of evidence of efficacy, vitamin B6 is widely prescribed (and self-prescribed) for the treatment of premenstrual syndrome.

Vitamin B6 for Prevention of the Complications of Diabetes Mellitus

A number of studies have suggested that vitamin B6 (and specifically pyridoxamine) may be effective in preventing the adverse effects of poor glycemic control that lead to the development of the complications of diabetes mellitus, many of which are mediated by nonenzymic glycation of proteins. Pyr-idoxamine is a potent inhibitor of the rearrangement of the immediate product of protein glycation to the 'advanced glycation end-product.'

Toxicity of Vitamin B6

Animal studies have demonstrated the development of signs of peripheral neuropathy, with ataxia, muscle weakness, and loss of balance, in dogs given 200 mg pyridoxine per kilogram body weight for 40-75 days, and the development of a swaying gait and ataxia within 9 days at a dose of 300 mg per kilogram body weight. At a dose of 50mgper kilogram body weight, there are no clinical signs of toxicity, but histologically there is a loss of myelin in dorsal nerve roots. At higher doses there is more widespread neuronal damage, with loss of myelin and degeneration of sensory fibers in peripheral nerves, the dorsal columns of the spinal cord, and the descending spinal tract of the trigeminal nerve. The clinical signs of vitamin B6 toxicity in animals regress after withdrawal of these massive doses, but sensory nerve conduction velocity, which decreases during the development of the neuropathy, does not recover fully. The mechanism of the neurotoxic action of vitamin B6 is unknown.

The development of sensory neuropathy has been reported in patients taking 2-7 g of pyridoxine per day. Although there was residual damage in some patients, withdrawal of these extremely high doses resulted in a considerable recovery of sensory nerve function.

There is little evidence that intakes of up 200 mg vitamin B6 per day for prolonged periods are associated with any adverse effects. The US Food and Nutrition Board set a tolerable upper level for adults of 100mg/day; the EU Scientific Committee on Food set 25 mg/day.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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