High pyridoxine diet in the rate: Implications for clinical megavitamin therapy

Megavitamin therapy has found increased clinical application. Although the toxicity of fat soluble vitamins is well established, little has been learned of the actions and fate of massive doses of the water soluble vitamins. Current interest in the use of vitamin B6 in the treatment of homocystinuria due to cystathionine synthase deficiency prompted us to explore its mode of action and metabolic side effects in the rat. Large amounts of pyridoxine in the diet had no effect on appetite but resulted in a 20% increase in body weight and 40% in liver weight of pair-fed controls. The fat/protein ratio and the percentage of each in liver was unchanged despite the increased liver weight. The weights of brain, pancreas and kidney were unaffected. There appeared to be an increase in peritoneal fat, however, the epiyimal fat pads were significantly smaller in the high-pyridoxine group becuase of smaller cell size. Concentrations of free amino acids were unchanged as were the activities of cystathionine synthase and cystathionase. Incorporation of 35S from both methionine and cystine into the proteins of various organs were also unchanged. In the rats on high-pyridoxine diets there was greater incorporation of 35S from cystine into reduced glutathione and less into oxidized glutathione. Since the amounts of pyridoxine consumed by the experimental group was of the order of magnitude as that currently used in the treatment of homocystinuria, further studies are needed before it can be assumed that massive doses of water soluble vitamins can be used with impunity.