Background:
It is well established that endogenous cholesterol synthesis has a diurnal rhythm. In contrast, no diurnal rhythm of intestinal cholesterol absorption was found in men adhering to a low-fat diet. Exploring the effect of dietary macronutrients on cholesterol metabolism is needed to understand whether meal composition may have a role in generating these rhythms. Hence, we performed a side-by-side comparison of a high-fat, high-carbohydrate, and high-protein meal on intestinal cholesterol absorption and endogenous cholesterol synthesis in apparently healthy overweight and slightly obese men.

Methods:
In this randomized, double-blind, cross-over study, men (n = 18) consumed an isoenergetic (953 kcal) high-fat (fat (f)/carbohydrates (c)/protein (p): 52.3 en%/ 39.2 en%/ 8.0 en%), high-carbohydrate (f/c/p: 9.6 en%/ 81.5 en%/ 8.6 en%), and high-protein (f/c/p: 10.6 en%/ 51.5 en%/ 36.9 en%) meal during three sessions separated by at least one week. The cholesterol absorption markers cholestanol, campesterol, and sitosterol, the cholesterol synthesis markers 7-dehydrocholesterol, 7-dehydrodesmosterol, desmosterol, dihydrolanosterol, lanosterol, lathosterol, zymostenol, and zymosterol, and total cholesterol concentrations were measured in serum in the fasted state and four hours postprandially.

Results:
Cholestanol, campesterol, sitosterol, and total cholesterol concentrations did not significantly change after intake of the three meals (all P > 0.05). A significant postprandial decrease was found for 7-dehydrocholesterol, lanosterol, lathosterol, zymostenol, and zymosterol (all P < 0.05). These postprandial effects did not significantly differ between the high-fat, high-carbohydrate, and high-protein meal (all P > 0.05), with the exception of dihydrolanosterol, which showed a significantly stronger decrease after high-fat compared to high-carbohydrate intake (P = 0.009).

Conclusion:
Meal consumption did not significantly change intestinal cholesterol absorption. Various endogenous cholesterol synthesis markers decreased over the postprandial period. These postprandial effects did not differ between the high-fat, high-carbohydrate, and high-protein meal, except for dihydrolanosterol.

The trial was registered on ClinicalTrials.gov under number NCT03139890 in May 2017.