Thursday, December 15, 2011
Mice, men, and the measure of resveratrol
Based on a small, brief, but nonetheless profound and compelling study in the current issue of the highly regarded scientific journal, Cell Metabolism, I intend to start taking resveratrol.
Rarely is anything that comes in a capsule or pill worth comparing to the power over medical destiny exerted by living well, good use of feet and forks in particular. Lifestyle can do what no pill can do. That will doubtless prove true of resveratrol as well, but thus far its promise looks all but unprecedented to me. The study in Cell Metabolism did, in fact, compare this particular pill to the power of lifestyle, and the pill measured up.
And rarely is it prudent to make a leap of faith from mice to men. Rodent studies often suggest benefits that fail to materialize when therapies are tested in humans. But having shown early promise in mice, resveratrol has nimbly made the leap to men (with, presumably, the same implications for women) in the new study.
The study in question assigned 11 obese but otherwise healthy men to 30 days of placebo and 30 days of 150 mg of resveratrol daily in random order. The study was double-blinded, meaning neither the participants nor the researchers knew who was taking what when. The fundamental study hypothesis, based on prior work in animals, was that resveratrol supplementation would mimic the effects of calorie restriction.
Calorie restriction has long shown promise for extending lifespan. Studies in a number of species have shown clear gains in longevity with administration of a nutritionally adequate, but calorically restricted diet (roughly 30% fewer calories than would be considered a "normal" level for maintenance of healthy weight). There have been no such studies in humans, for some fairly obvious reasons, salient among them the fact that if such an intervention worked, it would take longer than the researcher's lifespan to find out!
That said, the metabolic effects of calorie restriction in humans suggest opportunities for both health promotion, and life extension. But there are also some jokes attached to the notion of extending survival by practicing a state of carefully controlled, semi-starvation. Among the better ones: You may live forever, or maybe it will just feel that way. Or: It may well extend your life, but you'll keep wishing you would die!
Of course, adherents to so-called caloric restriction deny the downside, and report feeling vital while anticipating a long life. They intend to have the last laugh. Whether or not they get it, I wish them well.
But I also recognize that no matter what the benefits of calorie restriction, most people will not practice it. After all, we know there are profound benefits of controlling weight just by eating the recommended level of calories, and we can't get most people to do that! So 30% less? Fuggedaboutit.
Resveratrol is a compound concentrated in grape skin, and thus red wine. Early studies suggested it functioned as a potent antioxidant. While that might be of health benefit on its own, the history of isolated antioxidant supplements is one of perennial disappointment. Our high hopes for clear health benefits with supplements of vitamin C, beta-carotene, vitamin E, lycopene, and combinations have been consistently dashed. Meta-analyses of antioxidant trials suggest no benefit, and potential harm, serving up a starkly precautionary message.
But resveratrol is not just an antioxidant. It influences mitochondrial function and energy metabolism. And most importantly, resveratrol is a gene modifier. It influences the activity of a gene complex called SIRT1, which influences a wide array of metabolic activity, is considered a regulator of the "health span," and is the very gene complex influenced by calorie restriction.
The new study was published in Cell Metabolism for a reason, it reports changes in biochemical measures and cell biology and is thus a bit dense in its details. But the take-away message was clear enough. Daily dosing of resveratrol for a month mimicked most effects of calorie restriction, improving energy metabolism in muscle, improving insulin sensitivity, lowering blood pressure, and apparently enhancing fitness. There were no adverse effects of resveratrol.
Of course, there is much we don't know. The beneficial effects of resveratrol might wear off in time, or be too modest to matter. Or perhaps adverse effects might show up late. Calorie restriction, for instance, is associated with reduced fertility, and reduced libido. I count myself among those who would consider the latter of those effects too high a price to pay for any metabolic benefits. We don't know if resveratrol can facilitate weight loss, although that looks promising. We don't know, and won't for a very long time, if it can extend the human life span.
But we do have the first clear evidence that a natural compound can exert the same profound effects on metabolism, weight and genes, in humans, as calorie restriction. There is at least reason to hope a meaningful anti-aging effect could be appreciated as well.
Resveratrol has made the leap from mice to men. It will take some time to ascertain the true medical measure of this compound. While it is certainly premature to declare it a "wonder drug," I find myself wondering about that possibility. It's the best contender for a profound medical advance in a pill I have seen in a long time.
And so, I intend to try it for the next six months or so to see what effects I discern (less, of course, if I discern any I don't like). I can't yet recommend resveratrol to you with any great conviction, but I can share my excitement about its apparent promise, and I promise to share the results of my personal experience with it. Stay tuned!
David L. Katz, MD, FACP, MPH, FACPM, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care. He is a board certified specialist in both Internal Medicine, and Preventive Medicine/Public Health, and Associate Professor (adjunct) in Public Health Practice at the Yale University School of Medicine. He is the Director and founder (1998) of Yale University's Prevention Research Center; Director and founder of the Integrative Medicine Center at Griffin Hospital (2000) in Derby, Conn.; founder and president of the non-profit Turn the Tide Foundation; and formerly the Director of Medical Studies in Public Health at the Yale School of Medicine for eight years. This post originally appeared on his blog at The Huffington Post.
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Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.
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Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.
Suneel Dhand, MD, ACP Member
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Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.
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David Katz, MD
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