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Life Extension Magazine

LE Magazine March 2007
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Growing Evidence Links Resveratrol to Extended Life Span


By Laurie Barclay, MD

Specific Health Applications of Resveratrol

While resveratrol’s impact on cardiovascular disease has undergone the most scrutiny to date, researchers are also exploring its effects on a broad array of diseases, including cancer, arthritis, diabetes, and Alzheimer’s.16,17

Cardiovascular Health

One of resveratrol’s most studied applications involves the prevention of cardiovascular disease. “The cardioprotective effects of resveratrol have been studied for years, based largely on the association of wine consumption with reduced risk of coronary heart disease,” notes Dr. Zhao-Wilson.

This plant-derived compound appears to act through several mechanisms to protect the cardiovascular system. Resveratrol may inhibit platelets from clumping together, thus reducing the risk of deadly blood clots that can lead to heart attack and stroke.18-21 Furthermore, resveratrol helps improve blood flow by exerting beneficial effects on the linings of small blood vessels, known as the endothelium. This is a critical finding, since endothelial dysfunction is believed to underlie the progression of atherosclerosis.22-24

Does Resveratrol Explain the “French Paradox”?

Although French cuisine is world renowned for its rich sauces, gourmet cheeses, and fine wines, the French enjoy a relatively low incidence of coronary heart disease.12,13 This apparent anomaly has led scientists to wonder what dietary or lifestyle factors might account for the so-called “French paradox.” Studies suggest that resveratrol, a constituent of red wine, may help protect the French from the adverse health effects of their traditionally rich diet, while also protecting the liver against the toxic effects of alcohol.14

Technically, resveratrol is a chemical known as trans-3,5,4’-trihydroxystilbene. Produced by grapes, berries, peanuts, and certain other plants in response to stressful conditions, resveratrol and related biochemicals known as phytoalexins function as natural antibiotics, protecting plants against attack by pathogens.15

Life Extension recently discussed the French paradox with Milos Sovak, MD, founder of Biophysica, Inc., a California-based biomedical and pharmaceutical research company. According to Dr. Sovak, the hearty wines of southern France, produced from the Vitis vinifera vine, used to produce up to 30 mg of resveratrol per liter. This is no longer the case.

“The French who consumed up to 1 liter/day of wines originating in the South have had convincingly fewer cardiovascular afflictions than their brethren to the North,” says Dr. Sovak. “That situation is rapidly changing. With the advent of pesticides, plants are now producing almost no phytoalexins and it is rare today to find more than 2-3 mg of resveratrol per liter. That alone should be sufficient reason for supplementation with this compound regardless of the many studies—some reliable, some not—that show various advantages to red wine.”

Dr. Sovak notes that while grapes may no longer be a reliable source of resveratrol, this compound can be extracted from a shrub-like plant known as Polygonum cuspidatum, which originated in Japan and China but has since migrated to the United States and Europe. This plant contains high concentrations of resveratrol, up to 3-4%.

Cancer

In addition to its cardioprotective effects,25-27 resveratrol exhibits a range of anti-cancer properties.28 In laboratory cell studies, resveratrol has been found to inhibit the growth of numerous types of cancer, including leukemias, multiple myeloma, melanoma, and cancers of the breast, ovaries, prostate, stomach, colon, liver, pancreas, thyroid, uterine cervix, and head and neck.29,30

Resveratrol suppresses tumor growth by increasing or decreasing the production of various enzymes and molecules that regulate cellular reproduction and blood supply to the tumor.30,31 Through these mechanisms, resveratrol may enhance the anti-cancer effects of chemotherapeutic drugs and radiation.29 With its potent antioxidant capabilities,32,33 resveratrol may even protect healthy tissues from damage induced by chemotherapy. Since chemotherapy harms both healthy and cancerous tissues, this finding may have important applications in helping cancer patients tolerate its effects.34

Clinical trials in humans have shown that resveratrol has an excellent safety profile, and structural modifications of resveratrol with improved bioavailability are being studied as potential anti-cancer treatments.29

“Resveratrol is currently the subject of National Institutes of Health-sponsored clinical studies to evaluate its chemoprevention (cancer-preventive) effects,” according to Dr. Zhao-Wilson. An ongoing clinical trial at the University of California is studying resveratrol in patients with colon cancer.

Inflammation and Arthritis

A common culprit in heart disease, cancer, and arthritis is chronic inflammation, mediated by naturally produced compounds in the body known as prostaglandins and cytokines. By blocking the activity of such inflammatory compounds, resveratrol may have therapeutic applications for all of these conditions.35,36

In a recently published study, scientists reported that resveratrol shows promise as a potential therapy for arthritis. When administered to animals with experimentally induced inflammatory arthritis, resveratrol protected cartilage against inflammatory changes related to the disease.37

Neuroprotection

Resveratrol shows promise in protecting the brain and nervous system against disorders associated with aging and genetic factors. In laboratory studies, resveratrol’s antioxidant effect has been shown to protect against nerve cell damage caused by beta-amyloid peptide, which accumulates in the brains of Alzheimer’s sufferers.38-40 This has led several research teams to propose that resveratrol may be a useful treatment for Alzheimer’s disease.41-43

According to a recent report, resveratrol demonstrated a protective effect against Huntington’s disease in animal models.44 Huntington’s is a genetic disease associated with impaired motor skills and reduced mental abilities.

Additionally, grape seed extract appears to protect rat brain cells and maintain the overall viability of the nervous system. Grape seed exerts these effects by modulating proteins implicated in cognitive disorders.24

Diabetes

Resveratrol may offer benefits in preventing or managing conditions associated with high blood sugar, such as metabolic syndrome or diabetes. Sirtris Pharmaceuticals, a company founded by Dr. David Sinclair, leader of the Harvard resveratrol study, is conducting a clinical trial to evaluate resveratrol’s effects in controlling blood sugar in patients with diabetes.

BioMarker Pharmaceuticals: Pioneering Life Extension Research

BioMarker Pharmaceuticals was recently recognized by the Wall Street Journal as a pioneer in the field of resveratrol research. Based in San Jose, California, BioMarker is an innovative research institute dedicated to the study of lengthening and enhancing the quality of human life.

With support from the Life Extension Foundation, BioMarker is currently studying how resveratrol affects specific genes and cellular pathways to increase longevity. Leading these research efforts is Dr. Xi Zhao-Wilson, BioMarker’s chief scientist.

“BioMarker as a company is committed to conducting high-quality scientific research to support products that will help people live longer, healthier lives,” Dr. Zhao-Wilson told Life Extension. “The science in this area is young, but we are witnessing an explosion of information about how genes, proteins, specific molecular pathways, and normal and disease states are influenced by natural compounds like resveratrol. We believe this is just the tip of the iceberg, and that there will be tremendous advances in understanding the mechanisms underlying aging, and how these relate to diseases or maintenance of a disease-preventive state.”

Under Dr. Zhao-Wilson’s direction, BioMarker was one of the first companies to conduct a high-quality, controlled, single-dose study of resveratrol and grape extract in a large group of mice. BioMarker scientists compared mice given resveratrol and grape extract with a group of calorie-restricted mice. Using techniques of genetic analysis developed in collaboration with other research groups, the scientists then determined similarities and differences in gene expression in the groups of mice. Preliminary data analysis suggests that resveratrol’s benefits overlap with those of caloric restriction. Much like caloric restriction, resveratrol appears to offer tremendous promise in extending life span and improving quality of life.

According to Dr. Zhao-Wilson, “Our focus as a company is to pursue known and novel compounds . . . to understand the mechanisms underlying the disease-preventive and life-span-extending effects of interventions that mimic the beneficial effects of caloric restriction. Resveratrol . . . has been very helpful in elucidating some aspects of the total caloric-restriction picture.”

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