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Journal of Lipid Research, Vol. 47, 2820-2824, December 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

The lipid-lowering effect of ezetimibe in pure vegetarians

Jacob J. Clarenbach¹, Michael Reber¹, Dieter Lütjohann, Klaus von Bergmann and Thomas Sudhop²

Department of Clinical Pharmacology, University of Bonn, Bonn, Germany

Published, JLR Papers in Press, September 11, 2006.

¹ J. J. Clarenbach and M. Reber contributed equally to this work.

² To whom correspondence should be addressed. e-mail: sudhop{at}bfarm.de

ABSTRACT

Results of previous studies have shown that ezetimibe (10 mg/day) reduces LDL cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol diet (dietary intake of 200–500 mg/day) by 16–22%. However, the LDL cholesterol-lowering effect of ezetimibe in subjects with an extremely low dietary cholesterol intake (vegetarians) has not been studied. We conducted a randomized, double-blind, placebo-controlled, two-phase crossover study in 18 healthy pure vegetarians to assess the effect of ezetimibe (10 mg/day) on plasma lipids, cholesterol absorption, and its synthesis. Treatment periods lasted 2 weeks each, with an intervening 2 week washout period. Fractional cholesterol absorption was determined using the continuous dual stable isotope feeding method. Mean dietary cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 ± 16.8 and 31.4 ± 14.4 mg/day during the placebo and ezetimibe administration phases, respectively. Fractional cholesterol absorption during the placebo phase was 48.2 ± 8.2% and was decreased by 58% during ezetimibe treatment to 20.2 ± 6.2% (P < 0.001). This change in intestinal cholesterol absorption was followed by a significant reduction in LDL cholesterol of 17.3%. In individuals with extremely low dietary cholesterol intake, treatment with ezetimibe (10 mg/day) leads to a significant reduction of cholesterol absorption and a clinically relevant decrease of plasma LDL cholesterol, comparable to that of subjects with a normal dietary cholesterol intake. Thus, the lipid-lowering effect of ezetimibe is mediated mainly through a reduction of the absorption of endogenous (biliary) cholesterol.

Supplementary key words cholesterol absorption • cholesterol synthesis • campesterol • sitosterol • lathosterol

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