The lipid-lowering effect of ezetimibe in pure vegetarians.
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.
Clarenbach
Jacob J
JJ
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany.
Reber
Michael
M
Lütjohann
Dieter
D
von Bergmann
Klaus
K
Sudhop
Thomas
T
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000493:pharmacokinetics; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D014676:Diet, Vegetarian; D004311:Double-Blind Method; D000069438:Ezetimibe; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D013261:Sterols / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D013261:Sterols; D002784:Cholesterol; D000069438:Ezetimibe