Orlistat inhibits dietary cholesterol absorption.
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.


METHODS
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).


CONCLUSIONS
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.
Mittendorfer
B
B
Department of Internal Medicine and Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ostlund
R E
RE
Patterson
B W
BW
Klein
S
S
D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000201:enzymology; D007553:Isotope Labeling; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D000077403:Orlistat; D011446:Prospective Studies; D015203:Reproducibility of Results
D019440:Anti-Obesity Agents; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D007783:Lactones; D000077403:Orlistat; D008049:Lipase