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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.

Enter resveratrol.

Uva en Paterna (Valencia) by Herbolario Allium via Flickr and a Creative Commons licenseResveratrol 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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Blog log

Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Auscultation
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.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Richmond, Va., with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

DrDialogue
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

FutureDocs
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.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, 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.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

KevinMD
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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