Low dose niacin (50 mg/kg diet and 250 mg/kg diet) when supplemented in combination with leucine (24 g/kg diet) has a similar effect on lowering cholesterol in mice than standard therapeutic dose (1000 mg/kg diet) of niacin without leucine supplementation. Leucine amplifies niacin effect on lipid metabolism, hyperlipidemia and atherosclerosis in mice, at least in part by activation of the AMPK/Sirt1 axis.