Resveratrol Pennington Biomedical Research Center Division of Education Heli J. Roy PhD Shanna Lundy, BS Phillip Brantley, PhD, Director

PBRC 2005 Belongs to a class of polyphenolic compounds called stilbenes Some types of plants produce Resveratrol and other stilbenes in response to: –stress, injury, fungal infection, and ultraviolet (UV) radiation It is a fat soluble compound that occurs in a trans and a cis configuration RESVERATROL: General information

PBRC 2005 Both cis and trans resveratrol also occur as glucosides (bound to a glucose molecule) Resveratrol-3-O-beta-glucoside is also called piceid RESVERATROL: General information

PBRC 2005 Resveratrol is a phytoalexin, a class of antibiotic compounds produced as a part of a plant’s defense system against disease For example: In response to an invading fungus, resveratrol is synthesized from p-coumaroyl CoA and malonly CoA Since fungal infections are more common in cooler climates, grapes grown in cooler climates have a higher concentration of resveratrol RESVERATROL: General information

PBRC 2005 Food Sources Found in grapes, wine, grape juice, and berries of Vaccinum species including blueberries, bilberries, and cranberries In grapes, resveratrol is found only in the skins The amount of resveratrol in grape skins varies with the grape cultivar, its geographic origin, and exposure to fungal infection

PBRC 2005 Food Sources Also, the amount of fermentation time a wine spends in contact with grape skins is an important determinant of Its resveratrol content White and rose wines generally contain less resveratrol than red wines, which is because the skins are removed earlier during their production, lessening the amount that is extracted Red or purple grape juices may also be good sources of resveratrol

BeverageTotal resveratrol (mg/liter) Total resveratrol in a 5 ounce glass (mg) White wines (Spanish) Rose’ wines (Spanish) Red wines (Spanish) Red wines (global) Red grape juice (Spanish) Total Resveratrol Content of Wines and Grape Juice

FoodServingTotal resveratrol (mg) Peanuts (raw)1 c (146 g) Peanuts (boiled)1 c (180 g) Peanut butter1 c (258 g) Red grapes1 c (160 g) Total Resveratrol Content of Selected Foods

PBRC 2005 Although trans-resveratrol appear to be well-absorbed by humans when taken orally, its bioavailability is relatively low due to its rapid metabolism and elimination Information about the bioavailability of resveratrol in humans is important This is because much of the basic research on resveratrol has been conducted in cultured cells exposed to unmetabolized resveratrol at concentrations that are often times greater than peak concentrations observed in human plasma after oral consumption Metabolism and Bioavailability

DISEASE Prevention

PBRC 2005 Red wine polyphenols Significant reductions in cardiovascular disease risk have been associated with moderate consumption of alcoholic beverages Cardiovascular Disease

PBRC 2005 The French Paradox The French Paradox was the observation that mortality from coronary heart disease is relatively low in France despite relatively high levels of dietary saturated fat and cigarette smoking This led to the idea that the regular consumption of red wine might provide additional protection from cardiovascular disease Cardiovascular Disease

PBRC 2005 The French Paradox Red wine contains resveratrol and even higher levels of flavonoids These polyphenolic compounds have antioxidant, anti- inflammatory, and other potentially anti-atherogenic effects in the test tube and in some animal models of atherosclerosis Although moderate alcohol consumption has been consistently associated with 20-30% reductions in coronary heart disease risk, it is not yet clear whether red wine polyphenols confer any additional risk reduction Cardiovascular Disease

PBRC 2005 Resveratrol Resveratrol has been found to exert a number of potentially cardioprotective effects in vitro including: –Inhibition of platelet aggregation –Promotion of vasodilation by enhancing the production of NO –Inhibition of inflammatory enzymes But, concentrations of resveratrol required to produce these effects are often higher than those that have been measured in human plasma after oral consumption of resveratrol Cardiovascular Disease

PBRC 2005 Resveratrol Although its presence in red wine has stimulated much interest in the area of cardiovascular disease prevention, currently there is no convincing evidence that resveratrol has cardioprotective effects in humans Especially in the amounts present in 1-2 glasses of red wine Cardiovascular Disease

PBRC 2005 Resveratrol has been found to inhibit the proliferation of a variety of human cancer cell lines, including those from breast, prostate, stomach, colon, pancreatic and thyroid cancers when added to cells cultured outside the body In animal models, there has been marked inhibition in the development of esophageal, intestinal, and breast cancer with oral administration of resveratrol In mice, genetically predisposed to colon cancer, effects from oral resveratrol administration have been mixed Cancer

PBRC 2005 It is currently not known whether or not high intakes of resveratrol can help prevent cancer in humans Studies suggest that even very high dietary intakes of resveratrol may not result in tissue levels that are high enough to demonstrate the protective effects that resveratrol has shown in cell culture studies Cancer

PBRC 2005 Caloric restriction has been proven to extend the lifespan of a number of species, including mammals In yeast, a caloric restriction stimulates the activity of an enzyme referred to as Sir2 Administering resveratrol to yeast increased Sir2 activity in the absence of caloric restriction and extended the replicative lifespan of yeast by 70% Longevity

PBRC 2005 Although resveratrol did increase the activity of the homologous human enzyme (Sirt1) in the test tube, whether or not resveratrol can extend the human lifespan is currently unknown And again, the resveratrol concentrations that were necessary to increase Sirt1 activity in the test tube were considerably higher than any concentration previously measured in human plasma Longevity

PBRC 2005 Reasons why recommending a population-wide increase would be premature: 1.Little is known about the absorption and clearance of resveratrol, the identities of its metabolic products, or its effects on the liver 2.The research on resveratrol has focused on its short-term effects and has been dominated by in vitro studies on non- human models

PBRC 2005 Reasons why recommending a population-wide increase would be premature: 3.Its role as a potentiator of breast carcinomas may significantly limit its use, even for its proven benefits 4. Its main dietary source is red wine, which is not only extremely variable, but possibly harmful to be recommending increased intakes of red wine to the population at this point

PBRC 2005 At present, relatively little is known about the effects of resveratrol in humans In Conclusion…

PBRC 2005 SITES eratrol.htmlhttp:// eratrol.html