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Researchers find that weight loss drug blocks cholesterol absorption

Washington University In St Louis : 01 November, 2000  (Technical Article)
Washington University investigators have shown that a weight-loss drug, orlistat, can help prevent obese people from absorbing cholesterol from their food. They present their findings today at the annual scientific meeting of the North American Association for the Study of Obesity in Long Beach, Calif.
'This is the first time that a medication has been shown to block the absorption of cholesterol,' said Samuel Klein, M.D., the Danforth Professor of Medicine and Nutritional Science at Washington University School of Medicine in St. Louis. 'The results from our study suggest that orlistat therapy in obese patients may have beneficial effects on blood cholesterol that are independent of its effects on body weight.'

Previous clinical trials have shown that orlistat (commercially known as Xenical) blocks the absorption of dietary fat and that obese subjects who dieted and took orlistat lost more weight than those who dieted and took an inactive placebo. In addition, those who lost weight while taking orlistat had lower blood cholesterol levels than those who slimmed down without the drug. The Washington University researchers wanted to learn why.

'The results from large, clinical trials found that obese subjects who lost weight by dieting and taking orlistat with meals had a greater reduction in blood cholesterol concentration than those who lost the same amount of weight by dieting without orlistat,' said Klein, who also serves as director of the University’s Center for Human Nutrition.

Klein and colleagues hypothesized that the drug might interfere with the absorption of dietary cholesterol, just as it blocks absorption of dietary fat. So they studied cholesterol absorption in 20 volunteers, using a method developed by Richard E. Ostlund Jr., M.D., professor of medicine and a co-investigator in this study.

'The technique we used involves oral and intravenous administration of non-radioactive, stable isotope tracers of cholesterol. It allows us to accurately measure absorption from a standard meal,' Ostlund said.

When test subjects ate the meal with orlistat, they absorbed 25 percent less cholesterol than when they ate the test meal without the drug.

'The results from our study suggest that orlistat’s effect on cholesterol absorption may be the reason for its independent effect of reducing plasma cholesterol concentrations in obese patients,' Klein said.

Klein cautions that 'It is important to remember that the cornerstone of obesity therapy involves the difficult process of making lifestyle changes in dietary intake and physical activity. Orlistat and other drugs can be used as additional tools to help selected patients successfully achieve long-term weight management. But drug therapy should only be used as part of a comprehensive weight management program that includes medical exams, dietary counseling, education about physical activity and behavior modification.'
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