Orlistat inhibits dietary cholesterol absorption.

Author: Mittendorfer B, Ostlund RE Jr, Patterson BW, Klein S

Author affiliation: Department of Internal Medicine and Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Publication date & source: 2001.10, Obes Res., 9(10):599-604.

Publication type: Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.

OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low-density lipoprotein-cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration. RESEARCH METHODS AND PROCEDURES: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption. RESULTS: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.