Pfizer muddies the waters of red wine's fountain of youth

A key ingredient in red wine may not unlock the fountain of youth after all.

That's the conclusion from a study by Pfizer Inc. scientists in Groton who looked at a component of red wine called resveratrol. The scientists, led by Kay Ahn, published a paper last month in the Journal of Biological Chemistry that called into question previous research suggesting compounds like resveratrol may boost an enzyme that slows down the aging process.

"Efforts to slow the march of old age with a pill have been dealt a blow," concluded an article about the study in New Scientist magazine.

Nature magazine says the new study about resveratrol "deepens the divide between those who are confident in its potential and those who think it is too good to be true."

Despite the Pfizer study, authorities such as Philip Norrie, an Australian doctor who has written books about wine and health, said people shouldn't give up on resveratrol or the good health effects of drinking moderate amounts of their favorite red vintages.

Norrie, in an e-mail, questioned the Pfizer study, saying that it looked at resveratrol only as a direct activator of beneficial biochemical pathways.

"If it is an indirect activator/stimulator of a certain pathway, it would thus not show up as a direct activator to researchers such as in this instance with Pfizer, but it would still be causing the same resultant beneficial effect," he said. "Biochemical pathways are very complex with many interactions, checks and balances - it is not always simple and in a straight line."

"The overwhelming evidence is that moderate consumption of red wine leads to better health and lowers mortality," added Thomas Matthews, executive editor of Wine Spectator magazine, in a phone interview.

Dipak Das, a researcher at the University of Connecticut Health Center in Farmington and a national expert on resveratrol, agreed about the benefits of red wine and said in a phone interview that his research shows resveratrol in small doses can promote good health. He said there appears to be something about the way wine delivers resveratrol to the body that helps people derive benefits not seen in experimental scenarios.

"The benefit is without a doubt," said Das, who has been invited to address a National Institutes of Health seminar about the resveratrol controversy next month.

Das said resveratrol has to be delivered in a relatively small dose; larger doses can actually do damage. The formulation of the compound must also be as pure as possible to show the best effect, he said.

Bill Sardi, partner in a California firm that markets a so-called nutraceutical formulation of resveratrol called Longevinex, added that 60 milligrams of the drug can be found in a 5-ounce glass of wine, with maximum benefits derived by those who drink three to five glasses daily.

Sardi, a former health journalist, said studies of resveratrol have been hampered in the past by the lack of a biomarker to determine a beneficial effect. But he said in the past two years scientists have focused on the width of red blood cells as a good marker for how we age, giving hope that progress will be made.

Scientists have targeted resveratrol for study because it appears to activate an enzyme that protects cells from the kinds of damage that lead to aging. Resveratrol can be found in the skin of red grapes, though apparently not in significant enough quantities to explain the so-called "French paradox" noted by researchers looking to explain the low incidence of heart disease in France, despite the population's high-fat diet.

"Activation of this enzyme is thought to play a role in delaying the onset and reducing the incidence of age-related diseases including type 2 diabetes, as had been reported in scientific publications," Pfizer said in a statement.

But Ahn's team at Pfizer's research campus in Groton found, after "extensive biochemical and biophysical studies," that resveratrol as well as several other similar chemicals "are not direct activators" of this enzyme, according to company spokeswoman Liz Power.

Specifically, low doses of resveratrol did not help mice on a high-fat diet cut their blood-sugar levels, according to Ahn's study. And high doses of the drug killed three of the eight mice studied, Pfizer researchers said.

Pfizer did not make the local researchers available for interviews.

But Ahn, quoted in an article last month in Nature magazine, downplayed the significance of her study.

"Under our conditions we didn't see beneficial effects, but we don't want to make a big conclusion out of those results," she said.

The Pfizer team's research contradicted a highly publicized study done by Harvard University researcher David Sinclair and calls into question the assumptions behind new drugs being developed by Sirtris, a Massachusetts-based company purchased two years ago by GlaxoSmithKline for $720 million.

Sirtris has three experimental compounds in early- and mid-stage development that use proteins known as sirtuins against such diseases as cancer and diabetes.

Glaxo said in a statement that "scientific debate around the interpretation of data is a normal part of discovery in emerging areas of research."

But Glaxo said Pfizer's interpretation of data "is at odds with multiple studies conducted at Sirtris and those published by independent investigators."

The company added that the "purity of the compounds that were used in their study ... cannot be ascertained due to the lack of data provided. The publication also does not cite nor discuss multiple scientific publications which are in direct contrast to their primary conclusions; as such it is unclear how to place this work in perspective of what has been found by other investigators."

Glaxo said the Pfizer study appeared to be trying to prove a negative.

"The study falls short of that goal while adding little to the advancement of sirtuin biology," the company said.

The Pfizer scientists involved in the resveratrol study were listed as Michelle Pacholec, Boris A. Chrunyk, David Cunningham, Declan Flynn, David A. Griffith, Matt Griffor, Pat Loulakis, Brandon Pabst, Xiayang Qiu, Brian Stockman, Venkataraman Thanabal, Alison Varghese, Jessica Ward and Jane Withka.

Another study, published in an October issue of Chemical Biology & Drug Design by scientists from Amgen, found results similar to Pfizer's research.

As the science behind the ties between red wine and longevity becomes more controversial, resveratrol continues to be a favorite "miracle product" of fly-by-night marketers, said Sardi, the California businessman.

"Spammers have done more to sell resveratrol pills than any science," he said.

A one-month supply of the dietary supplements can sell for as little as $5, he reports, which is much cheaper than buying the aged red wines that he says bring the most beneficial health effects.

Still, Sardi conceded that marketing the benefits of red wine in pill form has drawbacks.

"You can't replace the romance and relaxation of wine," he said.

"Wine is our oldest medicine and best preventative medicine," added Norrie, a researcher known as The Wine Doctor.


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