We evaluated the effects of a three-carbon compound, pyruvate, on plasma lipid concentrations in hyperlipidemic patients consuming a high-cholesterol (560-620 mg), high-fat (45-47% of energy; 18-20% of energy as saturated fatty acid), anabolic diet (0.11-0.12 MJ/kg body wt) for 6 wk. Forty subjects consumed the diet, randomly supplemented with 36-53 g pyruvate (n = 19) or 21-37 g polyglucose (placebo, Polycose, n = 21) as a portion of carbohydrate energy. Plasma cholesterol and LDL-cholesterol concentrations were unchanged in the placebo group, but decreased by 4% and 5%, respectively, in the pyruvate group (P < 0.05 vs placebo). Plasma HDL-cholesterol, HDL3-cholesterol, and triglyceride concentrations were similar in both groups. Resting heart rate, diastolic blood pressure, and rate-pressure product were unchanged after 6 wk of therapy in the placebo group, but decreased by 9%, 6%, and 12%, respectively with pyruvate supplementation (P < 0.05 vs placebo). We conclude that pyruvate supplementation of a high-fat, high-cholesterol, anabolic diet will decrease plasma cholesterol and LDL-cholesterol concentrations without affecting the HDL-cholesterol concentration.