Drug Trial Raises Doubts About Resveratrol's Anti-Aging Powers

Just because something is natural doesn't mean it's safe.
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On December 2, pharmaceutical giant GlaxoSmithKline quietly halted a clinical trial of SRT501, a concentrated form of resveratrol, which is the much-hyped substance found in red wine grapes.

The reason this matters is that SRT501 had been one of the most closely watched molecules in the Big Pharma pipeline ever since 2008, when GlaxoSmithKline snapped it up in a $720 million acquisition of Sirtris Pharmaceuticals -- the company that first suggested resveratrol might be useful for treating age-related diseases.

SRT501 was being tested in a rare form of cancer called multiple myeloma, but Glaxo had grander plans for it and similar molecules. As Sirtris discovered, resveratrol modulates a gene called sir2, which produces the enzyme sirtuin. In mice, turning this gene on extends life by as much as 30 percent. Glaxo has been studying sirtuin-modulating drugs in a range of diseases common in aging people, including diabetes, psoriasis and colon cancer.

Resveratrol will no longer be part of that research, Glaxo says. Signs of trouble first emerged back in the spring, when the company halted the multiple myeloma trial because several patients developed kidney failure. Glaxo investigated, and concluded that the kidney complications may have stemmed from the underlying cancer, but that the SRT501 clearly didn't help matters. The resveratrol formulation "was not well tolerated, and side effects of nausea/vomiting/diarrhea may have indirectly led to dehydration, which exacerbated the development of the acute renal failure," said GSK spokeswoman Melinda Stubbee in an e-mail.

What scares me most about this news is that resveratrol is an incredibly popular over-the-counter supplement among healthy people who think it will help them live longer. Sales hit $30 million in 2008 and were forecast to double this year, according to Nutrition Business Journal. Resveratrol is widely available in mega-doses online and from health food stores.

And a lot of that excitement has been generated by Sirtris. The company's co-founder, Harvard scientist David Sinclair, became something of a media darling after he discovered resveratrol's effect on sir2 in the early 2000s. Sinclair was featured on "60 Minutes" and on an ABC News television special called "Live to Be 150 ... Can You Do It?" On the ABC program, which aired in 2008, Sinclair and Barbara Walters toasted each other with red wine, and Walters asked how many glasses she would have to drink to get the anti-aging benefits. "A thousand bottles a day," Sinclair answered.

Despite Sinclair's insistence that resveratrol's utility in humans had yet to be proven, media attention spawned an entrepreneurial free-for-all. Dozens of companies popped up offering free trials of resveratrol on the Internet. Some of them featured clips of Sinclair, as if to imply he had endorsed specific resveratrol supplements. (He had not.) Thousands of consumers were scammed into signing up for monthly shipments of resveratrol for $90 or more a month.

Many people believe the natural form of the red-wine supplement is perfectly safe and maybe even a lifesaver. Some blame Glaxo for somehow adulterating resveratrol when they turned it into a drug. A patient commenting last week on a Website for multiple myeloma patients called SRT501 "a corruption of the natural resveratrol molecule created by Glaxo to allow them to patent it and control the distribution through pharmaceutical channels."

But the fact is, "SRT501 is resveratrol," Stubbee says. It's purified and concentrated, but other than that, it's no different from the molecule found in your typical vineyard. Resveratrol seems to activate the longevity gene to some extent, but it's "not selective, meaning that it does many other things," she says. In the multiple myeloma trial, those things were not so pleasant.

Glaxo is now focusing on developing far more selective compounds, Stubbee says. They have no chemical relationship to resveratrol. "There are no further plans to develop SRT501."

To me, the moral of this story is clear: Just because something is natural doesn't mean it's safe. Sure, you can go to your local health food store and self-medicate with huge doses of resveratrol if you're so inclined. But if your goal is to live longer, I'd think twice.

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