Research Article: The journey of resveratrol from yeast to human

Date Published: March 12, 2012

Publisher: Impact Journals LLC

Author(s): Silvie Timmers, Johan Auwerx, Patrick Schrauwen.



The natural polyphenolic compound resveratrol was first discovered in the 1940s. In the recent years, this compound received renewed interest as several findings implicated resveratrol as a potent SIRT1 activator capable of mimicking the effects of calorie restriction, and regulating longevity in lower organisms. Given the worldwide increase in age-related metabolic diseases the beneficial effects of resveratrol on metabolism and healthy aging in humans are currently a topic of intense investigation.

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Resveratrol is a small polyphenol found in various berries, nuts, and other plant sources [6]. A number of studies have demonstrated that resveratrol and other polyphenols have a very low bioavailability, leading to the concern that many of the beneficial health effects observed in either cells or biochemical assays, may not be achievable in humans due to rapid metabolism [19]. So, one important question – though difficult to answer – is “what dose of resveratrol should be used?”.

The exact mechanisms through which resveratrol exerts a wide range of beneficial effects across species and disease models is currently still unclear [6]. Similar to most other polyphenols, resveratrol is suggested to possess intrinsic anti-oxidant capacity, but it is also implicated to induce the expression of a number of anti-oxidant enzymes, with probably both mechanisms contributing to an overall reduction in oxidative stress [32]. Resveratrol further interacts with a large number of receptors, kinases, and other enzymes that could plausibly make a major contribution to its biological effects.

In rodent models of diet-induced obesity, a high dose of resveratrol (400 mg/kg/d) improves insulin sensitivity and lowers body weight [10], which has increased the interest and the speculation about its potential use as an anti-diabetic agent in humans. However, applying a lower dose of resveratrol (~ 22.5 mg/kg/d) appeared insufficient to produce weight loss, although it still improved glucose tolerance [9]. In fact, low doses of resveratrol are shown to prolong survival in obese mice while simultaneously increasing body weight [29]. One observation that is made, is that animals supplemented with a high dose of resveratrol are capable of increasing their energy expenditure, based on their ability to increase their running distance or tolerate cold longer compared to their untreated controls. However, whether these observations underlie the reduction in body weight is not clear, as voluntary exercise is actually lower in the resveratrol-treated group and body temperature is not detectably changed under basal conditions [10]. Nevertheless, recent work has shown that a one-year intervention with resveratrol at a dose of 200 mg/kg/d seems to cause an increase in basal metabolic rate and total daily energy expenditure in the non-human primate Microcebus murinus [49, 50]; indicating that resveratrol might have the potency to enhance energy expenditure thereby promoting weight loss.





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