The profile of cholesterol metabolism does not interfere with the cholesterol-lowering efficacy of phytostanol esters

Background & aims: Increasing evidence suggests that high cholesterol absorption efficiency enhances the risk of atherosclerotic cardiovascular diseases. It is not known whether inhibiting cholesterol absorption has different metabolic effects in high- vs. low cholesterol absorbers. We evaluated the effects of phytostanol esters on serum lipids and cholesterol metabolism in a post hoc study of three randomized, double-blind, controlled trials. The participants were classified into low (n = 20) and high (n = 21) cholesterol absorbers by median cholesterol absorption efficiency based on the plasma cholesterol absorption marker cholestanol at baseline. Methods: The participants consumed mayonnaise or margarine without or with phytostanol esters for six to nine weeks without other changes in the diet or lifestyle. Serum cholesterol, cholestanol, lathosterol, and faecal neutral sterols and bile acids were analysed by gas-liquid chromatography. According to power calculations, the size of the study population (n = 41) was appropriate. Results: During the control period, cholesterol synthesis, and faecal neutral sterols and bile acids were lower in high- vs. low absorbers (p < 0.05 for all). Phytostanol esters reduced low-density lipoprotein cholesterol by 10-13% in both groups, and directly measured cholesterol absorption efficiency by 41 +/- 7% in low- and 47 +/- 5% in high absorbers (p < 0.001 for all) without side effects. Cholesterol synthesis and faecal neutral sterols (p < 0.01) increased in both groups, more markedly in the high vs. low absorbers (p < 0.01). Conclusions: Low cholesterol absorption combined with high faecal neutral sterol excretion are components of reverse cholesterol transport. Thus, high- vs. low absorbers had a more disadvantageous metabolic profile at baseline. In both groups, phytostanol esters induced favourable changes in serum, lipoprotein, and metabolic variables known to help in prevention of the development of atherosclerotic cardiovascular diseases. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).