Effect of dietary macronutrients on intestinal cholesterol absorption and endogenous cholesterol synthesis: a randomized crossover trial

BACKGROUND AND AIMS: Extensive research showed a diurnal rhythm of endogenous cholesterol synthesis, whereas recent research reported no diurnal rhythm of intestinal cholesterol absorption in males who consumed low-fat meals. Little is known about the acute effect of macronutrient consumption on cholesterol metabolism, and hence if meal composition may explain this absence of rhythmicity in cholesterol absorption. Therefore, we examined the effect of a high-fat, high-carbohydrate, and high-protein meal on postprandial intestinal cholesterol absorption and endogenous cholesterol synthesis in apparently healthy overweight and slightly obese males. METHODS AND RESULTS: Eighteen males consumed in random order an isoenergetic high-fat, high-carbohydrate, and high-protein meal on three occasions. Serum total cholesterol concentrations, cholesterol absorption markers (campesterol, cholestanol, and sitosterol), and cholesterol synthesis intermediates (7-dehydrocholesterol, 7-dehydrodesmosterol, desmosterol, dihydrolanosterol, lanosterol, lathosterol, zymostenol, and zymosterol) were measured at baseline (T0) and 240 min postprandially (T240). Meal consumption did not significantly change total cholesterol concentrations and cholesterol absorption marker levels (all p > 0.05). Serum levels of 7-dehydrocholesterol, lanosterol, lathosterol, zymostenol, and zymosterol decreased significantly between T0 and T240 (all p < 0.05). These decreases were not significantly different between the three meals (all p > 0.05), except for a larger decrease in dihydrolanosterol levels after the high-fat versus the high-carbohydrate meal (p = 0.009). CONCLUSION: The high-fat, high-carbohydrate, and high-protein meal did not significantly influence postprandial intestinal cholesterol absorption. Several cholesterol synthesis intermediates decreased postprandially, but the individual macronutrients did not differentially affect these intermediates, except for a possible effect on dihydrolanosterol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03139890.