Diet drug poisons kidneys, hampers cancer drugs

Thursday, December 13, 2012 by: David Gutierrez, staff writer
Tags: diet drugs, kidney damage, toxicity

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(NaturalNews) The popular weight loss drug orlistat, marketed under names including Alli and Xenical, is highly toxic to the kidneys and liver, and may interact dangerously with other drugs, according to a study conducted by a researcher from the University of Rhode Island and funded by the National Institutes of Health.

Researcher Bingfang Yan has already notified the FDA of his findings, some of which were published in the journal Biochemical Pharmacology.

Orlistat received FDA approval as a prescription drug in 1999. With the release of Alli in 2007, it became the first over-the-counter weight loss drug approved by the agency. According to Yan, it has been the most widely used weight loss drug in the United States for at least 10 years.

The drug works by preventing the intestine from absorbing fat. According to the conventional wisdom, orlistat itself also remains in the gut, unabsorbed.

"But orlistat is reportedly absorbed, and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption," Yan said.

Highly toxic

Even at the time of Alli's release, manufacturer GlaxoSmithKline admitted that approximately half of users could be expected to experience gastrointestinal side effects, including loose stools and anal leakage. But reports of more sinister side effects soon emerged, such that by 2010, the FDA issued a warning that users of orlistat should immediately contact a doctor if they suffered any of the symptoms associated with liver damage - anything from fever or fatigue to nausea, vomiting, stomach pain, brown urine or jaundice.

"Since it has been available over-the-counter, there has been a drastic increase of toxicity among patients using the drug," Yan said. "It has been linked to severe liver failure, acute pancreatic failure and acute renal [kidney] failure."

Now Yan has discovered the mechanism behind these problems: orlistat inhibits the enzyme carboxylesterase-2, which plays a major detoxifying role in the kidneys, liver and gastrointestinal tract. Even low levels of orlistat can cause severe and irreversible toxicity to internal organs, Yan found.

"When the activity of this enzyme drop[s] in those organs, toxicity increases or the efficacy of some drugs are altered," he said.

Just as troubling, the enzyme blocked by orlistat also plays an important role in helping the body metabolize a wide variety of drugs, from aspirin to several important cancer drugs.

"Alli-based interactions can be key factors in the efficacy of medicines," Yan said.

Yan found that when cancer cells were exposed to various cancer drugs along with orlistat, they multiplied more prolifically than when exposed to the cancer drugs alone.

"This study shows that orlistat profoundly alters the therapeutic potential of the anti-cancer drugs," Yan said. "In the case of the anti-cancer drugs, it weakens their effectiveness."

Although interfering with aspirin may seem like a more mild effect, that can also have serious consequences.

"Aspirin is used to treat blood clots," Yan said. "Orlistat would increase the therapeutic potential of aspirin, which may increase the tendency of bleeding."



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