Orlistat inhibits dietary cholesterol absorption

Objective: Orlistat decreases the absorption of dietary triglycerides by in hibiting 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 mechani sm for the independent effect of orlistat on plasma cholesterol concentrati on. Research Methods and Procedures: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class Il abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous admi nistration of intravenous ([H-2(6)] cholesterol) and oral ([H-2(5)] cholest erol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption wa s determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol a bsorption was determined with and without orlistat therapy in a prospective , randomized, crossover design to assess the effect of orlistat on choleste rol absorption. Results: In protocol 1, cholesterol absorption from the tes t meal was the same on both occasions (53 +/- 5% and 51 +/- 5%). In protoco l 2, orlistat treatment caused a 25% reduction in cholesterol absorption, f rom 59 +/- 6% to 44 +/- 5% (p < 0.01). Discussion: These data demonstrate that orlistat inhibits dietary cholester ol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.