Chemically, resveratrol is classified as a polyphenol, a broad group of plant-derived compounds further subdivided into other categories including the familiar group flavonoids, as well as tannins, lignins, and phenylpropanoids. One common source of resveratrol is wine, a drink that has recently gained notoriety for promoting some important health benefits. In a study of 25,000 people, Danish researchers recently determined that wine drinkers reduce their overall risk of dying from any cause (all-cause mortality) by roughly 40%.[1] Consequently, some believe resveratrol may be at least partially responsible for this beneficial health effect.

Because resveratrol forms in wine grapes in response to and as a defense against fungal infection, it is substantially present only in organic grapes—and predominately in red rather than white wines. Wine grapes grown by typical Western farming methods are treated so heavily with fungicides that resveratrol is produced only in very small quantities, e.g., less than one milligram per glass of red wine.

To qualify as a true calorie restriction mimetic (See Background), a substance must reduce the incidence of chronic diseases as well as activate genetic “switch” mechanisms which induce longevity, both of which occur in response to the calorie restriction protocol. Resveratrol seems to have both of these abilities by working through similar physiological mechanisms as CR. It is known to be a powerful antioxidant, inhibiting low-density lipoprotein (LDL) oxidation and scavenging hydroxyl radicals—a highly-reactive radical with a half-life of only 10-9 seconds, but capable of damaging amino acids, lipids, and nucleic acids. It also preserves levels of glutathione, the body’s master antioxidant.

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Resveratrol also boosts energy in the mitochondria, the reduction of which is a principal cause of aging and age-related chronic disease. Perhaps most interestingly, it is a gene expression modifier, as is calorie restriction. As such, both resveratrol and calorie restriction exert small quantitative effects on the level of expression of various genes. That is, they modulate (activate or inhibit) genetic pathways involved in life-span extension. Resveratrol’s life-extending capability may result from its ability to modify the SIRT2 gene, one of the family of sirtuin longevity-related genes.[2]

In the summer of 2003, Harvard researchers published a landmark study that shocked the anti-aging world.[3] The Harvard team demonstrated resveratrol—even in small amounts—is able to extend the life of yeast cells by 60-80%, as measured by the number of surviving generations. These results are similar to those obtained by caloric restriction. The researchers concluded that resveratrol activates a longevity gene in yeast cells in a fashion similar to the activation by calorie restriction of similar genes in the many animal species discussed. In other words, resveratrol extends survival by regulating a longevity gene or genes present in all life forms investigated, from yeast cells to humans.

By means of a sophisticated technique known as molecular pathway analysis, both resveratrol-treated as well as calorie-restricted animals show a significant overlap of modulated gene expression. Genes affected by resveratrol control over 100 key molecular pathways, including metabolism, DNA repair, and normal cell death. Apparently, it is the chemical structure of resveratrol rather than its other attributes (antioxidant properties, etc.) that is responsible for its gene-regulating ability.

In cancer studies, both in the laboratory (in vitro) and in animals (in vivo), resveratrol has been shown to inhibit cellular events associated with all three mechanisms of cancer formation—tumor initiation, promotion, and progression.[4] In laboratory cell cultures, it shows anti-cancer effects on many types cancer cells including breast, cervix, colon, esophagus, leukemia, lung, melanoma, neuroblastoma, ovary, pancreas, prostate, stomach, and thyroid.[5] Additionally, resveratrol increases the effectiveness of chemotherapeutic cancer drugs by sensitizing the targeted cancer cells, while at the same time reducing the toxic effects so characteristic of this class of drugs.[6]

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In 2004, a group of Taiwanese researchers showed that resveratrol-fed laboratory mice experienced delayed skin tumor-induced tumor formation, with fewer tumors per animal compared to the untreated control group.[7] Other researchers treated rats implanted with hepatoma cells, one of the most aggressive forms of cancer. Tumor growth and metastasis were reduced in two studies.[8] Resveratrol was further shown to enhance the efficacy and reduce the toxicity of the anti-cancer drug 5-FU.[9] Significant anti-tumor effects were shown in lab animals implanted with glioma, a type of brain tumor. Positive effects included slower tumor growth, higher survival rates, and longer survival times.[10] It has been noted that the powerful antioxidant effects of resveratrol may serve to inhibit healthy tissues from chemotherapy-induced damage.