Diet fat saturation and feeding state modulate rates of cholesterol synthesis in normolipidemic men.

To determine whether diets differing in fats affect cholesterol synthesis in normal individuals, nine men were randomly assigned to three groups that received three diets in a crossover design for 2 wk. Diets were either monounsaturated (MONO), polyunsaturated (POLY), or saturated (SAT). Subjects then drank a dose of deuterium oxide, and unesterified cholesterol fractional synthesis rates (FSR) were calculated during consecutive fed and unfed periods. Absolute synthesis was calculated as the product of FSR and pool size, the latter obtained from a decay curve following a [4-(14)C]cholesterol injection. Serum cholesterol concentrations varied with each diet consumed (P = 0.001); the SAT diet produced the highest and the POLY diet the lowest. Triglyceride concentrations were highest when subjects consumed the SAT diet and lowest with the POLY diet (P = 0.03); values obtained with the MONO diet did not differ significantly from those seen otherwise. HDL cholesterol concentrations were lowest when the SAT diet was consumed, highest when subjects were fed the MONO diet (P = 0.05), and midway but not significantly different with the POLY diet. Cholesterol FSR were greater when subjects consumed (P = 0.001) rather than not, and FSR during 12-h periods were greater (P = 0.045) when subjects ate the POLY diet rather than the SAT diet. Absolute synthesis was also greater (P = 0.04) when subjects were fed, but did not differ with fat type (P = 0.789). Results suggest that cholesterol synthesis is greater when men are fed than when they are not fed, and reduced synthesis is not responsible for the effect of different fats on cholesterol concentrations.