VITAMIN-B-6 NORMALIZES THE ALTERED SULFUR AMINO-ACID STATUS OF RATS FED DIETS CONTAINING PHARMACOLOGICAL LEVELS OF NIACIN WITHOUT REDUCING NIACINS HYPOLIPIDEMIC EFFECTS

Niacin (nicotinic acid) in large doses (>2 g) has been increasingly th e choice of lipid-lowering agent by clinicians. However, the potential risks of the use of high doses of the vitamin have not been criticall y considered in the same way as has the use of other lipid-lowering dr ugs. The present study provides evidence that pharmacological levels o f niacin interfere with the metabolism of methionine, leading to hyper homocysteinemia and hypocysteinemia. Male Sprague-Dawley rats were fed a semisynthetic diet supplemented with either 400 or 4000 mg niacin/k g (compared with 47 mg/kg diet in the control diet). In Experiment 1, feeding these diets for 3 wk resulted in a dose-related increase in th e plasma and urine methionine concentrations while cysteine levels wer e decreased. This altered methionine metabolism was accompanied by a l ower plasma vitamin B-6 concentration in niacin-supplemented rats comp ared with controls. In Experiment 2, the methionine and cysteine level s in plasma and urine were normalized when vitamin B-6 (10 mg/kg diet) was added to the diet containing 4000 mg niacin/kg and led for 6 wk. This experiment also showed that plasma and urine homocysteine concent rations were increased by niacin and normalized by vitamin B-6. The hy polipidemic action of niacin was unaffected by the presence of vitamin B-6. These results indicate that niacin at large dosages interferes w ith methionine metabolism by affecting vitamin B-6 status. The treatme nt of dyslipidemia with simultaneous administration of niacin and vita min B-6 could be a better therapy than the use of niacin alone.