Resveratrol: Of Mice and Men

We would all like to live longer. The most promising longevity research indicates that severe calorie restriction might extend life span, but such a diet is difficult to follow. Resveratrol, a phytochemical found in red wine, has been evaluated as a possible way out of the dilemma. When given to obese mice on a high calorie diet, it produced a number of changes associated with improved health, such as increased insulin sensitivity, and it increased survival. Perhaps by taking resveratrol you could eat as much as you want and get fat without suffering the usual consequences. Perhaps you could get the longevity benefits of severe calorie restriction without restricting calories.

In addition to fat mice, resveratrol also extends the life of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster (yeast, nematodes, and fruit flies). But a study in non-obese mice found no increase in survival (although it did find several signs of improved health). Besides the anti-aging claims, there is also some evidence from in vitro and animal studies that it might have cardiovascular effects and anti-cancer effects.

The ads for one product (Vinotrol) say:
• “Life is short… or maybe not.
• Top Harvard researcher says it’s “the Holy Grail of aging research.”
• As seen on CBS “60 Minutes.”
• Harvard Medical School, Johns Hopkins, Salk Institute and UC Davis Medical Research Proves that Powerful Red Wine Extract Holds the Secret to Living a Longer, Healthier and More Vibrant Life
• Has the “French Paradox” finally been explained?
• Trick your body into “aging in slow motion.”
• Can you live years longer and feel years younger?
• “extends the life of every species it’s been given to.”
• Vinotrol, with 50 mg of resveratrol derived from grapes and roots, provides the equivalent of the resveratrol in 278 five ounce glasses of Pinot Noir.
• Promoting circulation, blood flow, [what’s the difference between these two?] immune system [ Mark Crislip has recently explained to us what that means], energy and healthy arteries.
• In tiny print at the bottom, it offers this disclaimer:

 These statements have not been evaluated by the FDA. This product is not meant to diagnose or treat any disease. Vinotrol is not endorsed, associated or affiliated in any way with Harvard University, Johns Hopkins, Salk Institute or UC Davis Medical.

Dr. Stephen Barrett of Quackwatch has summarized the evidence for resveratrol at “Resveratrol: Don’t Buy the Hype.” It was recently evaluated by the “gold standard” publication The Medical Letter (Vol. 51 Issue 1321, p. 74-5, September 21, 2009). They pointed out “studies in humans are limited” and concluded

Resveratrol appears to produce some of the same effects as calorie-restricted diets that have reduced the incidence of age-related diseases in animals. Whether it has any benefit in humans remains to be established. 

The Natural Medicines Comprehensive Database says

There is insufficient reliable information available about the effectiveness of resveratrol.

Its safety has not been established, and there is speculation that it might potentiate certain cancers. The Natural Medicines Comprehensive Database concluded

 There is insufficient reliable information available about the safety of resveratrol when used in supplemental doses in amounts greater than those found in foods.

There are concerns about interactions with other drugs. It has antiplatelet effects and preliminary evidence shows that resveratrol might inhibit the cytochrome P450 enzymes, CYP3A, CYP1A, and CYP2E1.

Resveratrol products have been associated with scams and false advertising. Researcher Dr. David Sinclair is quoted in ads without his permission. He commented

His lab showed that mice fed the chemicals live at least 15% longer than normal mice. But to get such benefits, human beings might have to consume up to 5 grams of resveratrol a day, he says. That’s about 80 pills, at doses found in a typical bottle.

The properties of resveratrol are intriguing, and it may turn out to be a useful drug. But so far the studies on resveratrol are pre-clinical studies. We have no data on its effects in humans. Few people would want to take a proposed prescription drug that had not yet undergone clinical trials: why should resveratrol be any different? In the absence of clinical trials, resveratrol might be recommended for obese mice, but not for men.

Posted in: Herbs & Supplements

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8 thoughts on “Resveratrol: Of Mice and Men

  1. Dr Benway says:

    How to lie by telling the truth.

    Harvard Medical School, Johns Hopkins, Salk Institute and UC Davis Medical Research Proves that Powerful Red Wine Extract Holds the Secret to Living a Longer, Healthier and More Vibrant Life


    Vinotrol is not endorsed, associated or affiliated in any way with Harvard University, Johns Hopkins, Salk Institute or UC Davis Medical.

    Thanks to context and the way the brain resolves ambiguity when inspired to wish, people will read the above but only remember that researchers at these fine institutions found that Vinotrol makes you live longer.

  2. Scott says:

    And will the supplement hawkers take responsibility, or even attempt to find out, if these doses of resveratrol, say, cause strokes? Of course not.

  3. Enkidu says:

    My local sports talk radio station runs ads for Resveratrol constantly. A former NFL player even promotes it for them. Every time I heard the ad I wondered what in the heck the stuff was.

  4. Draal says:

    In vitro studies have shown that resveratrol activates the SIRTI gene which is presumed to be involved during calorie restriction. Dr. Sinclair identified resveratrol within a screening library a being a potent activator. He has subsequently identified a much more potent small molecule. He sold his company Sirtris to the tune of $720 million. So…. big pharma is impressed by the possibilities, big time. (Put that into your skeptical pipe and smoke it. :) )

  5. IR says:

    Just out of curiosity, did anyone see the segment on resveratrol being studied in rhesus monkey’s? Don’t hold me to it but I think it was a segment in a PBS program, NOVA or NOVA ScienceNow.

  6. KT says:

    For now, I will just drink lots of red wine. :) And eat small meals, I guess.

  7. Lawrence C. says:

    I am always amazed at how fast the latest cure is announced and marketed then shown to be, at the very least, inadequate to the claims. Already compounds called procyanidins are now thought to either be more important than resveratrol or working together with it (along with other chemicals in wine) to produce some beneficial effect.

    The only sensible thing to do, as KT notes, is to continue to drink red wine to get all the good stuff. :-)

  8. fyh78 says:

    The in vitro SIRT1 activation results are an artefact of the in vitro test. I says nothing about the in vivo workings of resveratrol.

    Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity.

    Resveratrol is a plant polyphenol capable of exerting beneficial metabolic effects which are thought to be mediated in large by the activation of the NAD(+)-dependent protein deacetylase SIRT1. Although resveratrol has been claimed to be a bona fide SIRT1 activator using a peptide substrate (Fluor de Lys-SIRT1 peptide substrate), recent reports indicate that this finding might be an experimental artifact and need to be clarified. Here, we show that: (i) the Fluor de Lys-SIRT1 peptide is an artificial SIRT1 substrate because in the absence of the covalently linked fluorophore the peptide itself is not a substrate of the enzyme, (ii) resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii) although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme. In consequence, our data challenge the overall utility of resveratrol as a pharmacological tool to directly activate SIRT1.

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