Resveratrol

What is Resveratrol?

Resveratrol is a naturally occurring substance that is found in the vines, roots, seeds, skins and stalks of grapes, peanuts, mulberries, the Japanese knotweed plant and several other plants. Resveratrol, along with other polyphenols including quercetin, catechins, gallocatechins, procyanidins and prodelphidins are extracted from grape seeds and skins and found in red wine. Commercial resveratrol supplements generally obtain their resveratrol from the Japanese knotweed plant.

Resveratrol is a phytoalexin. It is produced by plants in response to injury or fungal infections as a defense against pathogens that would injure the plant. Resveratrol may have anti-microbial activity for humans as well. Research suggests that resveratrol may improve heart and cardiovascular health, reduce the risk of cancer, fight some infections, and increase the life span of humans.

Resveratrol and Life Extension

Recent research has demonstrated that resveratrol may trigger a genetic expression that facilitates extended life span. This is the same life extension effect that is associated with calorie restricted diets. Restricting calorie intake in laboratory animals has been shown to prolong their life span by as much as 60%. The same effect has not been proven in humans, but the research is ongoing and looks promising. Restricted calorie diets, however, lack popularity. The possibility that resveratrol may provide a similar benefit has caused considerable interest.

Recent studies show that resveratrol activates molecular pathways involved in life-span extension. This effect has now been demonstrated in yeast, worms, flies, fish, and mice. While this effect has not yet been demonstrated in humans, research is ongoing and looks promising. Research with mice also demonstrates that resveratrol mitigates the harmful effects of high calorie diets, including metabolic changes resembling diabetes, liver and heart damage, and premature death. Resveratrol may enhance health and support longevity via multiple mechanisms, including potent antioxidant effects, enhancement of cellular energy production and influence of gene expression patterns in a manner similar to caloric restriction.

Resveratrol and Heart Health

Resveratrol and the other polyphenols in wine are believed to account for the so-called French Paradox. The French Paradox, the fact that the rate of coronary heart disease mortality in France is lower than observed in other industrialized countries, has been attributed to an increased consumption of red wine by the French.

Resveratrol inhibits the oxidation of low-density lipoprotein (LDL) cholesterol, inhibits smooth muscle cell proliferation and inhibits platelet aggregation. Resveratrol also reduces the synthesis of lipids in the liver and inhibits the production of proatherogenic eicosanoids by human platelets and neutrophils. Thus, it helps maintain healthy levels of blood lipids and cholesterol, reduces the formation of arterial plaque and reduces the hardening and thickening of arterial walls.

It is believed that some of the beneficial effects of resveratrol are a result of its anti-oxidant properties. These include the inhibition of LDL cholesterol oxidation and the increase in nitric oxide synthesis. Nitric oxide is involved in vasodilation and improved circulation.

The inhibition of platelet aggregation translates to a reduction in the tendency to form blood clots. Resveratrol, therefore, may reduce the frequency and severity of heart attacks and strokes. It has been proposed as an alternative to low dose aspirin for this purpose.

Resveratrol is an Anti-Oxidant

Resveratrol also has been found to exert a strong inhibitory effect on superoxide anion and hydrogen peroxide production by macrophages. It also has been demonstrated to decrease pro-inflammatory arachidonic acid release. It has hydroxyl-radical scavenging activity and glutathione-sparing activity.

Cancer and Resveratrol

Resveratrol is being actively researched as both a cancer preventive and treatment. Resveratrol is a broad-spectrum agent that stops cancer in many diverse ways, including blocking estrogen and androgens and modulating genes. Cancer types that may be responsive to resveratrol include colon, neuroblastoma, esophageal, breast (all types), prostate (all types), leukemia, bone, skin, pancreas, ovarian, melanoma, liver, lung, stomach, oral, cervical, lymphoma and thyroid.

p Recent research shows that resveratrol kills cancer cells whether they do or do not have the tumor suppressor gene. It also works whether cancer cells are estrogen receptor-positive or negative.

In addition to its direct anti-cancer properties, resveratrol may act as a synergist for other cancer treatments. For example, vitamin D3 converts to a steroid that inhibits the growth of breast cancer cells, and researchers have found that resveratrol increases the effect of vitamin D. Other research shows that it causes drug-resistant non-Hodgkin's lymphoma cancer cells to become susceptible to certain chemotherapeutic drugs. Additional research shows that resveratrol inhibits the ability of cancer cells to metastasize, particularly to bone.

The typical western diet contains a disproportionate amount of linoleic acid. Our bodies convert a portion of our dietary linoleic acid to arachidonic acid, which is converted to hormone-like substances that can promote inflammatory processes that stimulate cancer cell growth. In a study from Japan, resveratrol inhibited the growth of breast cancer cells and blocked the cancer growth-promoting effects of linoleic acid.

Alzheimer's and Resveratrol

p Alzheimer's patients produce an abnormal protein known as "beta-amyloid" in their brains. Beta-amyloid provokes increased levels of free radicals and oxidative stress which damages and kills brain cells. It has been hypotheized that resveratrol can protect the brain against oxidative stress, and keep cells alive. Research shows that adding additional anti-oxidants to resveratrol provides a greater degree of protection than from resveratrol alone. Additional anti-oxidants include vitamins C and E.

Researchers have also discovered that resveratrol actually promotes the clearance of amyloid-beta molecules that have already formed. Resveratrol apparently destroys amyloid-beta by producing intracellular proteosomes that attack and dissolve the amyloid-beta plaque. Researchers have also found that resveratrol activates a gene that prolongs lifespan and that this same gene protects the brain from damage from amyloid-beta plaque.

Resveratrol and the Herpes Family Viruses

Resveratrol has shown activity against herpes simplex virus types 1 and 2 in a dose-dependent manner. It appears to disrupt a critical early event in the viral reproduction cycle. Resveratrol was found to inhibit herpes simplex virus types 1 and 2 replication by the direct inactivation of HSV, not inhibition of virus attachment to the cell. Resveratrol was most effective when added within 1 h of cell infection, and not effective if added 9 h post-infection. Resveratrol was also found to delay the cell cycle reproduction and inhibit reactivation of virus from latently-infected neurons. These studies were performed on cells in vitro.

Researchers also tested 19% resveratrol cream on skin and vaginal herpes lesions in mice and compared the results with topical acyclovir. The results were similar for both substances.

Resveratrol Precautions

Since resveratrol is known to inhibit platelet aggregation and blood clot formation, individuals with bleeding disorders or taking anti-coagulant medications should consult their physician before using resveratrol supplements. The potential interaction of reveratrol with these conditions is unknown.

Other Resveratrol Considerations

It is known that most of the resveratrol taken orally is metabolized into derivative components in the digestive system and the derivative components are absorbed readily into the blood. It is also known that any resveratrol that makes it into the blood is quickly broken down to its derivative components by the liver. The question then comes, "how meaningful are those studies which measure the effects of resveratrol on cell cultures in the laboratory rather than the resveratrol derivatives that are found in the human blood"?

Some of the data referenced comes from human eipdemological studies, the observation of objective parameters such as blood tests in humans, animal studies and studies of cell cultures in the laboratory. It may be possible that some of the positive results reported from cell culture studies may not be duplicated by oral administration in humans. Yet, the positive results epidemological and clinical studies involving humans demonstrates that red wine and the red wine polyphenols including resveratrol do have positive health benefits when consumed orally.

The literature on recent resveratrol research is massive, but does not clarify this question. Additional studies involving resveratrol derivatives will be needed to clarify this question.

Resveratrol Dosage

An obvious question is, "what dosage of resveratgrol is necessary to produce an extension of human life span?" Some of the research with mice was done with a dosage of 22.4 mg. per kg. of body weight. That is the equivalent of 1629 mg. for a 160 pound adult human. Another study yielded similar results with an equivalent dose of 124 mg. per day for a 160 pound adult. Other sources claim positive results with doses of 20 mg. per day for a human. Translating dosages from animals to humans is an art at best and definitive dose ranging studies are still lacking.

So, what about getting your resveratrol from natural sources, like wine? It takes approximately 41 glasses of red wine to equal the resveratrol in one 20 mg. capsule. The negative effect of wine consumption is that alcohol is detrimental to health in a variety of ways especially when consumed in excess.

In addition, red wine is highly variable in resveratrol content. French farmers who demonstrated a lower incidence of heart disease consumed approximately one liter of red wine per day. At the time, it was estimated that one liter of wine contained approximately 20 mg. of resveratrol. However, the wide spread use of pesticides and fungicides in vineyards has led to a drastic reduction in the resveratrol content of wine. Recall that resveratrol is produced in the grapes as a defense against damage and fungus attack. With no bugs and fungus, the grapes don't need to make resveratrol any longer. So, if you are looking for wine or grapes or growing your own, go organic and go for humid conditions that promote fungus. It is possible that grape varieties that are naturally fungus resistant may also be higher in resveratrol as well.

Resveratrol Supplements

Here are some recommended Resveratrol Supplements.

Resveratrol Supplements

Resveratrol References

Click to Expand References

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