Published online in Nature Structural and Molecular Biology, the study is the first to report how the drug orlistat (Xenical or Alli) binds and interacts with a protein found in tumor cells. The drug blocks the protein's function and causes cell death. The project started five years ago when Steven Kridel, Ph. D., an assistant professor in the Department of Cancer Biology, analyzed prostate cancer cells to see which enzymes were expressed at high levels. His hope was that treatments to inhibit those enzymes could also stop tumor growth. “We found that a protein known as fatty acid synthase is expressed at high levels in prostate tumor cells, and is fairly absent in normal cells,” said Kridel. Other research has shown that the protein is found in many tumor cells including breast, colon, ovarian, liver, lung and brain. A study released today sends out a strongly worded warning about risks of kidney, liver, and other organ damage from the most popular weight drugs on the market. According to a University of Rhode Island study funded by the National Institutes of Health (NIH), orlistat, which goes by the prescription brand name Xenical and the over-the-counter name Alli, can cause "severe toxicity" to major internal organs. The research results obtained by pharmacology professor Bingfan Yan were worrying enough that he immediately reported the results to the FDA, which approved orlistat in 1999. Liver and kidney damage are serious enough, but Yan's team also reported another finding, just as concerning, that orlistat's metabolic action reduces the effectiveness of many medications, including life-saving cancer treatments. In fact, the researchers reported that cancer cells multiplied faster under the influence of orlistat. Orlistat also boosts the anti-clotting effects of aspirin, raising the risk of bleeding both internal and external. Yan and his team found that orlistat - even at low doses - limits the function of a key enzyme called carboxylesterase-2, which has an important role in detoxifying the liver, kidneys, and entire gastrointestinal tract.
This medication is used with a doctor-approved exercise, behavior change, and reduced-calorie diet program to help you lose weight. It is used by certain overweight people, such as those who are obese or have weight-related medical problems. Taking orlistat can also help keep you from gaining back weight you have lost. Losing weight and keeping it off can lessen the many health risks that come with obesity, including heart disease, diabetes, high blood pressure, and a shorter life. Dietary fats need to be broken down into smaller pieces before the body can absorb them. Orlistat works by blocking the enzyme that breaks down fats in your diet. This undigested fat then passes out of your body in your bowel movement. Objective To examine the risk of colorectal cancer after orlistat initiation in the UK population. Setting Data from the UK Clinical Practice Research Datalink from September 1998 to December 2008. Participants 33 625 adults aged 18 years or over who started treatment with orlistat; each orlistat initiator was matched to up to five non-initiators (n=160 347) on age, sex, body mass index, and calendar time. Main outcome measures Associations between orlistat initiation and the risk of colorectal cancer, assessed by calculating hazard ratios with propensity score adjusted Cox proportional hazard models. Results Of 193 972 patients with a median age of 47 (interquartile range 37-57) years, 77% were women and approximately 90% were obese (body mass index ≥30). Orlistat initiators were more likely to have a previous history of diabetes or hypertension and to receive prescriptions for anti-diabetes drugs, statins, and aspirin compared with non-initiators. In the intention to treat analysis, 57 colorectal cancer events were identified among orlistat initiators and 246 among non-initiators, with median follow-up times of 2.96 and 2.86 years, respectively. The calculated incidence rate of colorectal cancer per 100 000 person years was 53 (95% confidence interval 41 to 69) for orlistat initiators and 50 (44 to 57) for non-initiators.
Read about hernia pain, types of hernias, surgery, surgery complications, and treatment. Learn the signs and symptoms of hernias in men, in women, and in children. A. Aug 27, 2013. It is limited by the relatively short follow-up time, and the possibility of adverse effects of long term orlistat use on risk of colorectal cancer cannot.