Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism

Background: High-carbohydrate diets improve plasma cholesterol concentratio ns but increase triacylglycerol concentrations; the latter effect increases the risk of cardiovascular disease (CVD). Triacylglycerol concentrations i ncrease only during very-high-carbohydrate diets consisting mainly of simpl e sugars. Objective: We compared the CVD risk profile, cholesterol metabolism, and gl ucose tolerance of 7 healthy subjects during 2 isoenergetic diets: a high-f at, low-carbohydrate diet (HF diet) and a moderately high-carbohydrate, low -fat diet (HC diet). Design: In a randomized crossover study, we measured the effects of the HF diet [40% carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15% polyunsaturated)] and HC diet [55% carbohydrate (mainly complex) and 3 0% fat (10% saturated, 10% monounsaturated, and 10% polyunsaturated)] (3 wk each) on plasma lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the messenger RNA (mRNA) concentrations of beta -hydrox y-beta -methylglutaryl coenzyme A (HMG-CoA) reductase, the LDL receptor, an d the LDL-receptor-related protein (LRP). Results: Compared with the HF diet, the HC diet lowered total, LDL, and HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL c holesterol; triacylglycerol concentrations were unchanged. Lower cholestero l concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05) and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL rece ptor mRNA concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and oral glucose tolerance was better (P < 0.05) with the HC d iet. Conclusion: The beneficial effects of the HC diet on glucose tolerance and plasma cholesterol concentrations without increases in triacylglycerol show that this diet had favorable effects on both insulin sensitivity and the p lasma lipid profile.