History of Resveratrol
 trans-Resveratrol In 1940, Resveratrol was identified as the active component in Cassia quniquangulata (cinnamon) extract and was shown to be responsible for the anti-inflammatory properties of Polygonum cuspidatum roots, used in traditional Chinese and Japanese medicine (Takaoka). Since then, studies have shown that resveratrol is a member of a class of compounds called phytoalexins, which are used as a defense mechanism in plants in response to pathogens. Grapes, blueberries, and bilberries produce appreciable levels of resveratraol, and thus the main sources of resveratrol in the human diet are red wine, grape juice, peanuts, and cranberry juice. The discovery of Resveratrol in wine (1992), implicated a role for this compound in underlying the “French Paradox”, i.e., the observation that French exhibit a relatively low risk of cardiovascular disease even though they exhibit a diet that is high in saturated fats [4].
Health Benefits of Resveratrol
 History of Resveratrol Citatitions on PubMed Notice Semilog Plot A PubMed search for “resveratrol”, indicates that scientific interest in the health benefits of resveratrol is growing exponentially. To date, a diverse array of health benefits have been associated with resveratrol, including:
1. Improved insulin sensitivity. Resveratrol has been shown as a potent therapeutic for type 2 diabetes [27]. Pharmaceuticals based on resveratrol-like compounds for the treatment of diabetes are currently in Phase I clinical trials [28].
2. Inhibits carcinogenesis. Resveratrol induces cell death specifically in cancerous cells. This property has been demonstrated for a variety of cancers, including colon [5-7], pancreatic [8], prostate [9,10], breast [11,12], and skin [13,14] cancer. Several ongoing phase I human clinical trials are investigating resveratrol as a cancer therapy [15,16]
3. Extended lifespan. Resveratrol mimics the effects of caloric restriction in mammals and has been shown to extend lifespans in invertebrates [29,30], anda fish model [31]. In addition, resveratrol reduces the genetic changes associated with aging in a mammalian mouse model [4,18,32]. PGC-1alpha levels was decreased threefold by induction of genes for oxidative phosphorylation and mitochondrial biogenesis in wt SIRT1 mice but no change in SIRT1(-/-) MEFs [33].
4. Improved cardiovascular function. Resveratrol exhibits cardioprotective effects, such as the suppression of atherosclerosis, inhibition of platelet aggregation, vasorelaxation promotion, and modulation of triglyceride blood levels [1-4].
5. Reduced Neurodegeneration. Mouse models of Alzheimer's and Parkinson's disease have provided evidence that resveratrol functions as a protective agent against degenerative neural diseases[22,23]. In addition, Experiments with rats, mice, and gerbils show that resveratrol administration protects against brain damage following isochemic stroke [24-26].
6. Decreases inflammation. NEED A SENTENCE OR TWO SUMMARIZING THESE CITATIONS [18-21].
Our understanding of Resveratrol effects on cellular function is currently too limited to explain the biochemical origin of the diverse pharmacological effects that have been observed to date.
Rationale for Creating Resveratrol-Enriched Beer
One of the best sources of resveratrol is wine, with red wine having concentrations ranging from 0.1 to 14.3mg/L and white wine having concentrations ranging from <0.1 to 2.1mg/L (Sinclair). Unfortunately, the abundance of resveratrol in this beverage is thought to be too low to allow for all of the health benefits that have been demonstrated in model organisms, beneficial effects have been shown at levels readily achieved in humans [4].
Beer is also expected to contain resveratrol. Hops that is used to flavor beer contains 0.5 to 1 µg resveratrol/g (Sinclair review), and beer is produced under fermentative conditions, which is likely to prevent the air oxidation and inactivation of resveratrol from the hops. While the levels of resveratrol in beer are less than that of wine, beer represents >85% of all alcoholic beverages consumed in the US (National Institute on Alcohol Abuse and Alcoholism), and thus a better vehicle for widespread delivery of air-sensitive prophylactics like resveratrol. To increase the level of resveratrol present in beer, we are working to engineer a brewers yeast that synthesizes resveratrol from tyrosine.
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