出版社：American Society for Biochemistry and Molecular Biology
摘要：Results of previous studies have shown that ezetimibe (10 mg/day)reduces LDL cholesterol in patients with mild hypercholesterolemiaon a normal-cholesterol diet (dietary intake of 200–500mg/day) by 16–22%. However, the LDL cholesterol-loweringeffect of ezetimibe in subjects with an extremely low dietarycholesterol intake (vegetarians) has not been studied. We conducteda randomized, double-blind, placebo-controlled, two-phase crossoverstudy in 18 healthy pure vegetarians to assess the effect ofezetimibe (10 mg/day) on plasma lipids, cholesterol absorption,and its synthesis. Treatment periods lasted 2 weeks each, withan intervening 2 week washout period. Fractional cholesterolabsorption was determined using the continuous dual stable isotopefeeding method. Mean dietary cholesterol intake in the purevegetarians was extremely low and averaged 29.4 ± 16.8and 31.4 ± 14.4 mg/day during the placebo and ezetimibeadministration phases, respectively. Fractional cholesterolabsorption during the placebo phase was 48.2 ± 8.2% andwas decreased by 58% during ezetimibe treatment to 20.2 ±6.2% (P < 0.001). This change in intestinal cholesterol absorptionwas followed by a significant reduction in LDL cholesterol of17.3%. In individuals with extremely low dietary cholesterolintake, treatment with ezetimibe (10 mg/day) leads to a significantreduction of cholesterol absorption and a clinically relevantdecrease of plasma LDL cholesterol, comparable to that of subjectswith a normal dietary cholesterol intake. Thus, the lipid-loweringeffect of ezetimibe is mediated mainly through a reduction ofthe absorption of endogenous (biliary) cholesterol.Supplementary key words cholesterol absorption • cholesterol synthesis • campesterol • sitosterol • lathosterol
