Objectives-Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear. Methods and Results-We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR. Conclusion-Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48. Key Words: apolipoprotein Ⅲ high-density lipoprotein Ⅲ kinetics Ⅲ lipid-lowering medications Ⅲ triglyceride T he cholesterol-lowering effect of the vitamin nicotinic acid, or niacin, was first reported by Altschul et al 1 more than 50 years ago. Since then, treatment with pharmacological doses of niacin has been found to significantly lower the risk of coronary heart disease (CHD). 2,3 Several trials have also tested the effect of niacin in combination with other lipid-lowering medications on CHD risk, overall showing a beneficial effect. 4 -6 Niacin primarily decreases plasma triglyceride (TG) levels and very low-density lipoprotein (VLDL) cholesterol (C) levels and increases plasma highdensity lipoprotein (HDL)-C levels. 2,7 It has been hypothesized that the reduction in TG and VLDL-C is mediated by the niacin-associated inhibition of free-fatty acid (FFA) release from the adipose tissue, which may lead to reduced substrate availability for TG synthesis and secretion in hepatic cells. 8 However, a study conducted in 1 hypertriglyceridemic subject showed faster clearance of autologous 125 Ilabeled VLDL after niacin treatment. 9 Niacin is one of the most potent HDL-C-raising agents currently available. Two previous studies have attempted to elucidate the effect of niacin on HDL metabolism in young normocholesterolemic subjects. 10,11 The first study was conducted in 2 subjects and found an increase in HDL-C levels associated with a slower HDL catabolism with niacin. 10 The second study, in 5 young healthy subjects, found a significant increase in plasma HDL-C and apolipoprotein (apo) A-I levels with niacin withou...