Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin's hypolipidemic effects

Niacin (nicotinic acid) in large doses (>2 g) has been increasingly the choice of lipid-lowering agent by clinicians. However, the potential risks of the use of high doses of the vitamin have not been critically considered in the same way as has the use of other lipid-lowering drugs. The present study provides evidence that pharmacological levels of niacin interfere with the metabolism of methionine, leading to hyperhomocysteinemia and hypocysteinemia. Male Sprague-Dawley rats were fed a semisynthetic diet supplemented with either 400 or 4000 mg niacin/kg (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 the plasma and urine methionine concentrations while cysteine levels were decreased. This altered methionine metabolism was accompanied by a lower plasma vitamin B-6 concentration in niacin-supplemented rats compared with controls. In Experiment 2, the methionine and cysteine levels 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 concentrations were increased by niacin and normalized by vitamin B-6. The hypolipidemic action of niacin was unaffected by the presence of vitamin B-6. These results indicate that niacin at large dosages interferes with methionine metabolism by affecting vitamin B-6 status. The treatment of dyslipidemia with simultaneous administration of niacin and vitamin B-6 could be a better therapy than the use of niacin alone.