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. 
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.
Labels: David Katz, diet, diet calorie restriction, guest post, lifestyle, longevity, supplements
posted by David L. Katz, MD at
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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.
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.
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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