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

Maite M Schroor,Jogchum Plat,Maurice C.J.M Konings,Ellen T.H.C Smeets,Ronald P Mensink

doi:10.1016/j.numecd.2021.01.010

Maite M Schroor, Jogchum Plat + Show 3 more

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https://doi.org/10.1016/j.numecd.2021.01.010

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Abstract

Background and aimsExtensive 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 resultsEighteen 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). ConclusionThe 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 registrationClinicalTrials.gov, NCT03139890.

Highlights

Whole body cholesterol homeostasis is tightly regulated by endogenous de novo cholesterol synthesis, intestinal biliary and dietary cholesterol absorption, and bile acid synthesis and excretion [1]
The aim of this study was to compare in apparently healthy overweight or slightly obese men the effects of high-fat, high-carbohydrate, and high-protein meals on markers reflecting intestinal cholesterol absorption and endogenous cholesterol synthesis
Healthy men consumed low-fat diets throughout the study. Since it is well-known that external factors, including the diet, may influence these fluctuations over time [21], we questioned whether the low-fat diet might have been the reason for the lack of rhythmicity in intestinal cholesterol absorption

Summary

Introduction

Whole body cholesterol homeostasis is tightly regulated by endogenous de novo cholesterol synthesis, intestinal biliary and dietary cholesterol absorption, and bile acid synthesis and excretion [1]. I.e. campesterol and sitosterol, and the cholesterol metabolite cholestanol reflect fractional intestinal cholesterol absorption, while the cholesterol precursors lathosterol and desmosterol reflect whole body endogenous cholesterol synthesis [2,3]. 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. 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). Serum levels of 7dehydrocholesterol, 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 Z 0.009).

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