NIH resveratrol study raises varied concerns among experts

A new study by the National Institutes of Health sheds light on the action of resveratrol in cells. One resveratrol supplier has hailed the results, while another believes it promotes a pharmaceutical application, as opposed to a dietary supplement.

Researchers with the National Institutes of Health say they have identified a possible method of action for resveratrol. The study used mice to show that resveratrol affects the activity of sirtuin 1, a protein associated with aging, via an indirect as opposed to a direct pathway.

“This is good news. Despite well-documented health benefits of resveratrol, the mechanism of action has been elusive,” said Michael I. McBurney, PhD, head of scientific affairs for DSM Nutritional Products. DSM markets a nature-identical form of resveratrol under the ResVida brand.

Several previous studies suggested that resveratrol's primary target is sirtuin 1. The lead author of the study, Jay H. Chung, MD, PhD, and his colleagues suspected otherwise when they found that resveratrol activity required another protein called AMPK. This would not be the case if resveratrol directly interacted with sirtuin 1. The study found that resveratrol inhibits certain types of proteins known as phosphodiesterases (PDEs), enzymes that help regulate cell energy.

“It has been hypothesized that the health benefits of resveratrol are modulated through energy-sensing pathways involving the sirtuin family of proteins, but the mechanism of action was unknown. These findings from the NIH are intriguing because they provide insight,” McBurney said.

While the NIH study is promising, it won’t affect the messaging surrounding ResVida in the short term.

“In nutrition, understanding mechanisms of action is of paramount importance. However, DSM bases its resVida claims on clinical studies in humans,” McBurney said.

This study comes on the heels of other recent research on resveratrol’s effects. A study in 2011 published in Cell Metabolism showed that 150mg daily of resveratrol lowered subjects’ resting metabolism, mimicking the effect of a calorie-restricted diet.

Where does resveratrol research go from here?

Resveratrol research has had a rough go lately. In January, prominent resveratrol researcher Dr. Dipak Das of the University of Connecticut was accused of falsifying the data included in up to 150 studies. Many of the allegations centered on the use, or misuse, of western blots, which are graphic representations of protein analysis.

An internal audit by the university censored Das. Some industry sources came to Das’ defense, contending that it is common practice to alter these blots to improve legibility. Others pointed to the large number of positive studies that don't have Das' name on them.

But Das’ work centered on resveratrol’s affect on cardiovascular health. His difficulties have not dimmed the prospects for research into resveratrol’s anti-aging properties.

Dr. David Sinclair, a resveratrol researcher at the Harvard Medical School, was quoted by CBS News as saying, "there is a comprehensive body of literature in mouse and rats indicating that resveratrol is effective in preventing numerous diseases in those animals, including type II diabetes, neurodegeneration, fatty liver and inflammation. These results would not be in question, even if some of his work is retracted."

The NIH study does raise issues about the potential toxicity associated with resveratrol supplementation, a warning that is unfounded according to resveratrol expert Bill Sardi, who manufactures Longevinex, a resveratrol supplement. Sardi said the dosage level is critical with resveratrol—too little and there is no effect, too much and the molecule can start to act like pro-oxidant as opposed to an antioxidant. Many studies have used a 1gm/day dosage, Sardi said, in order to provoke a vigorous effect. Lovgevinex, on the other hand, has a recommended dosage of 100mg/day of resveratrol, combined with quercetin.

Sardi was critical of the use of the pharmaceutical Rolipram as a control in the study. The study authors claimed Rolipram “reproduced all of the biochemical effects and health benefits of resveratrol.”

“The study itself removes the cloud over the initial gene target of resveratrol,” Sardi said. “However the NIH is leading us to the doorstep of using drugs that inhibit that gene target, when resveratrol is far safer and should be considered the primary agent to work on that gene pathway.”

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