Speakers: Joseph Baur (University of Pennsylvania) and Nick Venditti (Frankly Wines)Presented by the Sackler Institute for Nutrition Science and Science & the City
Reported by Jaclyn Jansen | Posted September 6, 2012
It is hard to imagine a way to improve the appeal of a glass of red wine and a bar of chocolate; indeed, most people need little incentive to indulge more often. Yet recent research suggests that perhaps we should do just that. A few years ago, resveratrol—a compound found in red wine and dark chocolate—made a splash in the news as an anti-aging wonder. Although resveratrol may offer health benefits and has shown some signs of affecting longevity in laboratory models, research is only in its early stages. Since the media touts a new food as a fountain of youth almost daily, it can be difficult to separate the facts from the sales pitches. To explicate the latest research behind these claims, the Sackler Institute for Nutrition Science and Science & the City presented a seminar titled The Science Behind the Hype: Resveratrol in Wine & Chocolate on June 5, 2012. Joseph Baur, a biomedical research scientist at the University of Pennsylvania, described his research into resveratrol's action and explained studies that indicate some promising results, from improved cardiovascular health to alleviated diabetic symptoms. The seminar also delved into the practical applications of this research—how to choose the best glass of wine—with a presentation of local wines by Nick Venditti from Frankly Wines.
The search for a mechanism to slow aging and prolong life has pervaded human history; literature is filled with references to a “fountain of youth” that could keep us in the prime of our lives. While scientists have made great strides in treating and curing disease, little is known about how to increase longevity in an otherwise healthy individual. Until recently, research into the mechanisms underlying aging and longevity has been regarded as “pseudoscience.” Some have argued that such research is futile because the aging process is too complex; however, scientists have made some notable progress in the area. For example, some studies in the roundworm C. elegans have found that mutation of just one gene can dramatically increase its lifespan. Furthermore, while some argue that human lifespan has reached a plateau, Baur pointed to an analysis by Oeppen and Vaupel claiming that over the past 150 years humans’ maximum lifespan has increased steadily and shows no sign of slowing. According to Baur, fears that extended life could pose a public health crisis because “the older you get the sicker you get,” are unwarranted. Baur cited studies demonstrating that individuals who live longer are generally healthier throughout their lives and represent a smaller burden on the healthcare system than those with a shorter lifespan.
Conventional wisdom suggests that there are many steps we can take to increase our life expectancy and researchers have quantified these effects. For instance, quitting smoking can add almost ten years to life expectancy, exercising regularly can add five years, reducing weight (body mass index) can add from 2 to 10 years depending on the weight differential, and it is estimated that curing cancer could add three years. In contrast, antioxidant supplements have shown almost no benefit. Perhaps surprisingly, one epidemiological study by Streppel and others suggested that consuming about half a glass of red wine each day increases lifespan by approximately five years; its alcohol content may account for two of these years (alcohol has some cardiovascular benefits), but other compounds must be responsible for the additional three. Likely candidates are found in a class of compounds known as polyphenols, a large and diverse group of antioxidants found in many foods, including red wine, blueberries, chocolate, coffee, and tea. Resveratrol is a polyphenol that is relatively specific to red wine and chocolate and is produced most abundantly in plants grown under conditions of environmental stress. It has documented protective neurological and cardiovascular benefits and is commonly used in Asian medicinal herbs.
How is resveratrol linked to longevity and aging? Baur explained that it emerged as a compound of interest out of a large body of aging-related research. A number of studies in organisms ranging in complexity from yeast to Rhesus macaques have suggested that caloric restriction can increase maximum lifespan and promote health. [Editor’s note: A recent study by Mattison et al., did not confirm the prior report of lifespan extension in Rhesus macaques, although caloric restriction still delayed the onset of cancer and diabetes]. Investigating how caloric restriction works to extend lifespan, researchers identified a gene in yeast called Sir2 (SIRT1 in mammals) that may be involved. In a search for agents to activate SIRT1, researchers screened over 20,000 molecules: resveratrol emerged as the top hit. Subsequent research has demonstrated that resveratrol treatment promotes increased lifespan in organisms as varied as yeast, worms, and fish.
Resveratrol may mimic the effects of caloric restriction to increase lifespan and slow aging in a variety of organisms by activating the Sir2 gene. This experiment found that the Sir2 gene must be present for resveratrol treatment to result in lifespan extension. (Image courtesy of Joseph Baur)
Tests in mammals—most informative for determining potential efficacy in humans—have revealed significant health benefits. Obese mice treated with resveratrol had improved motor function and had gene-expression profiles similar to those found in calorie-restricted mice. Baur’s group found that treating mice on a high calorie diet with resveratrol reduced fasting insulin levels, returned livers to normal size, and restored lifespan to that of lean mice, consistent with experiments in other organisms. It is important to note that these effects were independent of weight loss, as the obese mice did not become leaner.
Resveratrol shows promise for improving health outcomes as we age and for promoting longevity, but many questions remain. Baur noted that it did not extend the lifespan of lean mice, as it did that of obese mice, suggesting that our understanding of caloric restriction and longevity is incomplete and further work in this area is needed. In addition, the molecular mechanisms of resveratrol’s action have been difficult to determine and are still disputed. Research is underway to determine whether resveratrol works by binding directly to the SIRT1 enzyme or activates SIRT1 through a different mechanism. Resveratrol has numerous known targets in addition to SIRT1, and may exert its effects through any number of these; its anti-diabetic effects, for example, were observed in SIRT1-knockout mice. In contrast, its effect on mitochondria biogenesis was shown to be dependent on the presence of SIRT1.
Although resveratrol is already marketed in anti-aging products, human clinical trials are in fact only now underway. There are more than forty studies examining its effect on a slew of ailments, including cancer, diabetes, and even cellulite. Although the end results of these studies have yet to be reported, clinical trials assessing safety have found that doses of up to about one gram are generally well tolerated by most individuals (one bottle of wine contains only five milligrams); nonetheless, Baur noted that larger long-term studies are required to determine whether the compound is safe overall. Small trials have begun to report promising results for the use of resveratrol to treat some health problems. For example, one study showed increased blood flow to the brain, with possible beneficial effects on cognition; another found improvements in insulin sensitivity in pre-diabetic older adults. When combined with statins, resveratrol reduced risk factors associated with cardiovascular disease. In another small study, obese men treated with resveratrol for just 30 days exhibited outcomes consistent with caloric restriction, including decreased insulin resistance, decreased inflammatory markers in the blood, some reduction of fat content in the liver, and increased ability of mitochondria to oxidize fat. Notably, this was the first study to use a low enough dose of resveratrol to be obtainable from a nonlethal dose of red wine—the equivalent of about two bottles per day. Another study found improved heart attack survival and improved ventricular function with doses within a range that could be obtained from red wine. Although research is in early stages, results from small studies indicate promise of efficacy in humans.
Chocolate also contains resveratrol, but in much lower quantities than red wine. Research into the possible benefits of chocolate has been mainly observational in nature. Moderate chocolate intake has been associated with a reduced risk of heart attack and large-scale analysis of the existing literature suggests that chocolate consumption can reduce LDL cholesterol levels and blood pressure. Baur noted that it is difficult to recommend chocolate as a source of resveratrol because of its high fat and sugar content.
Nick Venditti from Frankly Wines followed Baur’s presentation with a discussion of the benefits of choosing local wines. Resveratrol is found in the highest concentration in thick-skinned grapes that are grown in a stressful environment; the climate in New York is much less hospitable than other areas, making local New York wines rich in resveratrol. In addition to the health benefits derived from their high resveratrol content, Venditti offered other incentives to drink New York wines: these wines tend to be more cost effective than their Californian counterparts and are an investment in the local area. Venditti concluded his discussion with some suggestions for how to taste wine, and participants had the opportunity to test his methods on samples offered after the presentation. As we await definitive results from human trials, we can hope to extend our lives while enjoying a glass of red wine and a bite of chocolate.
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Presentations available from:
Joseph Baur (University of Pennsylvania)
Nick Venditti (Frankly Wines)