High cholesterol absorption efficiency interferes with bile acid metabolism and cholesterol elimination from the body

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BACKGROUND: Elevated low-density lipoprotein (LDL) cholesterol causes atherosclerotic cardiovascular diseases. Variables of whole-body cholesterol metabolism, for example, high cholesterol absorption efficiency, might also be atherogenic, whereas the role of bile acids is controversial. OBJECTIVES: This post hoc study concerns the impact of cholesterol absorption on bile acid metabolism. The hypothesis was that cholesterol absorption efficiency interferes with bile acid metabolism. METHODS: Cholesterol metabolism was studied using absolute and relative methods. Elimination of cholesterol from the body as bile acids and neutral sterols was assessed from 24-h faecal collections and analysed by gas-liquid chromatography. Cholesterol absorption efficiency was evaluated by a peroral continuous dual-isotope feeding method, and cholesterol synthesis by a sterol-balance technique. The relative methods included analyses of serum biomarkers of cholesterol absorption efficiency and cholesterol synthesis by gas-liquid chromatography. RESULTS: Faecal bile acids, neutral sterols and cholesterol synthesis were lower in high- versus low-cholesterol absorbers. Elimination of cholesterol from the body as bile acids and neutral sterols was reduced in high- versus low-cholesterol absorbers. Serum and LDL cholesterol levels did not differ in low- versus high-cholesterol absorbers. Absolute and relative methods of cholesterol metabolism correlated with each other, suggesting that the results can be considered valid. CONCLUSION: In high-cholesterol absorbers, poor elimination of cholesterol from the body as bile acids and neutral sterols may indicate an increased risk of atherosclerosis. It can be prevented by decreasing cholesterol absorption and increasing reverse cholesterol transport by dietary means combined with ezetimibe and statin treatment, when needed.

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