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Journal of Lipid Research, Vol. 46, 2692-2698, December 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe

Lily Jakulj^*, Mieke D. Trip, Thomas Sudhop, Klaus von Bergmann, John J. P. Kastelein^* and Maud N. Vissers^1,*

^* Departments of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany

Published, JLR Papers in Press, September 14, 2005. DOI 10.1194/jlr.M500260-JLR200

¹ To whom correspondence should be addressed. e-mail: m.n.vissers{at}amc.uva.nl

Consumption of plant sterols and treatment with ezetimibe both reduce cholesterol absorption in the intestine. However, the mechanism of action differs between the two treatments, and the consequences of combination treatment are unknown. Therefore, we performed a double-blind, placebo-controlled, crossover study for the plant sterol component with open-label ezetimibe treatment. Forty mildly hypercholesterolemic subjects were randomized to the following treatments for 4 weeks each: 10 mg/day ezetimibe combined with 25 g/day control spread; 10 mg/day ezetimibe combined with 25 g/day spread containing 2.0 g of plant sterols; 25 g/day spread containing 2.0 g of plant sterols; and placebo treatment consisting of 25 g/day control spread. Combination treatment of plant sterols and ezetimibe reduced low density lipoprotein cholesterol (LDL-C) by 1.06 mmol/l (25.2%; P < 0.001) compared with 0.23 mmol/l (4.7%; P = 0.006) with plant sterols and 0.94 mmol/l (22.2%; P < 0.001) with ezetimibe monotherapy. LDL-C reduction conferred by the combination treatment did not differ significantly from ezetimibe monotherapy (–0.12 mmol/l or –3.5%; P = 0.13). Additionally, the plasma lathosterol-to-cholesterol ratio increased with all treatments. Sitosterol and campesterol ratios increased after plant sterol treatment and decreased upon ezetimibe and combination therapy.

Our results indicate that the combination of plant sterols and ezetimibe has no therapeutic benefit over ezetimibe monotherapy in subjects with mild hypercholesterolemia.

Supplementary key words low density lipoprotein • humans • sitosterol • hypercholesterolemia

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