January 2012 Issue

Is Resveratrol a Panacea? — Evidence Shows It May Protect Against Many Diseases
By Karen Lilyquist, PhD, RN, RD, LD
Today’s Dietitian
Vol. 14 No. 1 P. 46

Suggested CDR Learning Codes: 2000, 4040, 5120, 5150, 5160; Level 2

Unlike many products that claim to be the next fountain of youth but quickly lose their celebrity status, resveratrol, a phytochemical, may be held in high esteem for quite a while. Found in grape skins, red wine, certain berries, nuts, peanuts, and dietary supplements, resveratrol is highly touted to promote vitality, wellness, and longevity and combat chronic disease. There’s considerable hype and intriguing research behind resveratrol.

This continuing education activity will evaluate the current evidence surrounding this phytochemical, its mechanism of action, and its protective effects against a host of chronic illnesses.

The French Paradox
In the early 1990s, research emerged to support anecdotal evidence about the health benefits of red wine, specifically its serum lipid-lowering effect. Much of this anecdotal evidence, largely known as the French Paradox, came as a result of observing the French, who have low coronary heart disease (CHD) death rates despite a high intake of saturated fat.1 The French diet derives 35% to 40% of its calories from fat, including 16% from saturated fat.1,2 The US diet comprises roughly the same amount of fat,3 yet the French have considerably lower mortality rates from CHD.

Because of this, researchers focused on one significant difference in their dietary habits: The French drink considerably more red wine than Americans. In a study1 that examined the French paradox, Ferrières noted that “wine consumption has been associated with a decrease of 24 to 31% in all-cause mortality; little to moderate wine drinking leads to lower mortality from cardiovascular disease than an equivalent consumption of beer or spirits.”

This distinction is important: Not just alcohol, but red wine in particular, is cardioprotective. Other researchers concurred,4 and recent preliminary studies indicate that wine also may play a role in protecting against essential tremors,5 certain cancers,6,7 Huntington’s disease,6 diabetes and obesity,7 and dementia. Moreover, it’s linked to enhanced lung function and increased longevity.8

The substances in wine that contribute to these health benefits are called polyphenols, a type of phytochemical. One kind of polyphenol, phytoalexins, is produced in grape skins to protect the grapes from pathogenic bacteria, fungal infections, and environmental stresses. Resveratrol (trans-3,5,4’-trihydroxystilbene) is one phytoalexin. Resveratrol and other phytoalexins have been referred to as a plant’s “antiaging weapons.”9

Mechanism of Action
Resveratrol’s chemical structure gives it the ability to activate sirtuins, a family of enzymes that play a critical role in a wide variety of processes in the body, including gene expression, metabolism, and aging. It’s hypothesized that if resveratrol can successfully stimulate the human sirtuin genomes, it can suppress DNA instability and repair damaged DNA, thereby reducing disease development and increasing longevity.

Early research documented resveratrol’s effects on life span in yeast,10 fruit flies, nematode worms,11 and short-lived fish,12 but these findings recently have been challenged. Burnett and colleagues13 reexamined the key experiments linking sirtuin to longevity in animals and found that animals with higher levels of sirtuin lived longer than controls. But when they took precautions to differentiate the controls and test subjects only according to sirtuin levels, the longevity effect disappeared. Other studies had similar findings, leading to the conclusion that genetic factors other than sirtuin genes were responsible for the longevity.

Despite this conflict, it appears resveratrol has an effect similar to that of caloric restriction, blunting the age-related decline in heart function.14 This finding will need to be replicated in humans before researchers can make any therapeutic claim, but previous studies have laid the groundwork.

Resveratrol has been found to inhibit the proliferation of a variety of human cancer cells, protect against diabetes-related complications, and hinder plaque formation that leads to Alzheimer’s disease. However, much more research is needed.

Protective Effects Against Chronic Disease
Following is a summarization of the current evidence on resveratrol’s effects on specific diseases and conditions.

Cardiovascular disease: As mentioned, moderate red wine consumption has long been known to reduce the risk of heart disease, in part because of the relaxing effect of alcohol. However, polyphenilic compounds, including resverstrol, have an antioxidant, anti-inflammatory, antiatherogenic effect in vitro. The compound trans-resveratrol has been shown to help block platelet aggregation in humans.15 This antiaggregating property thins the blood or makes it less sticky, thereby lowering the risk of blood clots that can cause stroke, heart attack, and other blood vessel diseases.

Moreover, resveratrol appears to prevent free radical oxidation of LDL cholesterol,16 which is the beginning of a cascade of cellular events that lead to plaque buildup in arteries, or atherosclerosis.17

Resveratrol, along with quercetin, appears to be beneficial for hypertension because it has a vasodilator effect on blood vessels17 by enhancing the production of nitric oxide and preventing free radical damage to blood vessels. (Quercetin is a yellow powdered crystalline compound that occurs as a glycoside in the rind and bark of numerous plants.) Some findings in animal studies suggest that high oral doses of resveratrol could decrease the risk of thrombosis and atherosclerosis16 but not all report this positive effect.18 Convincing evidence that resveratrol has cardioprotective effects in humans, particularly in the amounts consumed in a glass or two of wine, is lacking, and the early enthusiasm for this possible claim has waned. Nevertheless, the French Paradox remains.

Cancer: Carcinogenesis is a complicated multistep process. All cancers begin when mutations, changes, or damage occur in a cell’s DNA, resulting in the uncontrollable growth and spread of abnormal cells. In contrast, normal cells reproduce in an orderly, controlled fashion. Exposure to a substance that alters cellular DNA starts the process. Genetic, viral, or environmental carcinogens produce free radicals, which can damage a cell’s DNA, leading to the first stage of cancer development called initiation.

Resveratrol was found to act as both an antioxidant and antimutagenic in rat models,19 thus potentially inhibiting the development of certain cancers. In these studies, resveratrol increased levels of phase 2 detoxification enzymes that attach carcinogens to other molecules that act as carriers to remove them from the body.

Resveratrol appears to interfere with the promotion of cancer cells, the stage during which damaged cells grow and multiply uncontrollably, resulting in tumor development, growth, and proliferation. Resveratrol was found to inhibit the proliferation of various tumor cells in vitro, including lymphoid and myeloid cancers; melanoma; multiple myeloma; squamous cell, ovarian, and cervical carcinoma; and cancers of the breast, colon, pancreas, prostate, stomach, and thyroid.20 Even more intriguing, resveratrol is thought to help repair damaged information in cell DNA21 and encourage apoptosis of damaged cells.22 There’s much excitement about the proposed ability of resveratrol to arrest the unchecked growth of DNA-damaged cells, which crowd out healthy cells and damage surrounding tissue.

In the third stage of cancer development, also known as progression or metastasis, malignant tumors grow and migrate to other parts of the body. Metastasis has long been considered irreversible; however, findings that resveratrol inhibits the proliferation of a variety of human tumor cells in vitro has led to multiple preclinical animal studies to determine the potential of this compound for cancer chemoprevention and therapy. A study by Bishayee22 suggests that “resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis.”

However, data must be interpreted cautiously. The current research has focused on short-term, in vitro effects in animal models in which the cancer has been artificially induced by experimental means; it’s unknown whether high intakes of resveratrol can prevent cancer in humans. Data suggest the effectiveness of resveratrol in vivo is limited due to poor systemic bioavailability,23 and studies on human metabolism and resveratrol suggest that even high doses of the phytochemical may be insufficient to realize the protective effects demonstrated in the in vitro studies.24

Diabetes: Resveratrol appears to protect against neuropathy caused by poorly controlled diabetes. In one study,25 resveratrol injections provided renal damage protection, as determined by significant improvement in renal function and a decrease in oxidative stress.

Diabetic neuropathy is a common sign of oxidative stress. One study26 found that resveratrol therapy reduced the effects of neural changes and DNA fragmentation damage associated with diabetic neuropathy. Another study reported resveratrol therapy contributed to a decrease in pain due to diabetic neuropathy.27

Retinopathy is a diabetes complication that’s also a major concern, as it often leads to blindness. Resveratrol has been shown to prevent oxidation in retinal epithelial cells, thereby protecting against damage to the retinal blood vessels in the eyes.28

In addition, resveratrol may be beneficial in the prevention and treatment of age-related macular degeneration, a major cause of vision loss worldwide. The potential role of resveratrol in preventing blindness is promising, but much more research is required before researchers can reach any firm conclusions or offer recommendations.

Obese mice fed a high-calorie diet supplemented with resveratrol experienced an increase in insulin sensitivity, along with improvements in other markers that indicated better blood glucose control.12 Other studies have corroborated these findings and have found that resveratrol may improve fasting blood glucose levels and oral glucose tolerance.29 Recent clinical trials in humans suggest that resveratrol lowers blood sugar levels. Findings from this research, conducted by a pharmaceutical company, were discussed in review articles but haven’t been published in peer-reviewed journals.

Alzheimer’s disease: The causes of Alzheimer’s are unknown, but it is known that information transfer at neuronal synapses in the brain begins to fail. This likely develops because of multiple factors rather than a single one.

In Alzheimer’s disease, the brain is characterized by a buildup of plaques and twisted tangles of beta amyloid proteins that block neural pathways and disconnect the memory and brain circuit pathways.30 In one study,29 resveratrol was shown to significantly reduce plaque formation in animal brains. It appears to degrade some beta amyloid proteins and may even block the production of new types of beta amyloids,31 thus reducing the amyloid plaque buildup associated with aging.

A strong antioxidant, resveratrol can help protect against free radical oxidation of fatty acids in the brain32 and reduce inflammation and neurological deterioration of the brain, delaying the progression of Alzheimer’s disease.33 One mouse model found that resveratrol supplementation improved the cognitive ability of mice who already had Alzheimer’s disease.34

Menopausal symptoms: Researchers have discovered that resveratrol is a phytoestrogen, which means it can mimic the effects of estrogen and may be beneficial as a natural treatment for menopausal symptoms. In general, phytoestrogens have been shown to relieve hot flashes and mood swings and stabilize the reduction of postmenopausal bone density.35

Viral infections: In a few studies, resveratrol has been shown to play a role in inhibiting Influenza A,36 the varicella-zoster virus,37 and HIV viral factors.38 Resveratrol increases the potency of some antiretroviral drugs against HIV in vitro. Moreover, it’s been shown to suppress the replication of the herpes simplex virus.39

Autoimmune diseases: Resveratrol has been found to produce apoptosis of inflamed and damaged cells of the spinal cord, suggesting possible treatment in multiple sclerosis patients.40 It’s also worked with the sirtuin family in the brain to protect the dopaminergic neurons that become damaged in Parkinson’s disease.41 Due to its ability to help with inflammation, resveratrol is being researched for lung diseases like chronic obstructive pulmonary disease, emphysema, and asthma. Furthermore, it’s been found to protect against fatty liver disease.42

Food and Supplement Sources
The most abundant natural sources of resveratrol are the grape varieties common, muscadine, and catawba. Raspberries, mulberries, blueberries, bilberries, cranberries, and peanuts contain the compound as do some inedible plants such as eucalyptus, spruce, lily, Scots pine, eastern white pine, and Japanese knotweed.

Environmental factors influence the amount of resveratrol in grapes. Resveratrol is synthesized in response to invading fungi and since fungal infections are more common in cooler climates, grapes grown in these regions have higher concentrations of the phytochemical. Grapes grown in cold, mold-friendly climates (eg, France’s Bordeaux region and the Willamette Valley of Oregon) produce grapes with higher resveratrol content than those grown in dry, temperate climates. Unhealthy or stressed grapes have the highest concentration of resveratrol.

Resveratrol concentrations also are related to the length of time grapes remain in their skins during the fermentation process. Red wine is fermented with the skins, allowing the liquid to absorb the resveratrol; the skins are removed during white wine production, reducing the amount of resveratrol that’s extracted.43 Scant amounts of resveratrol are found in grape meat.

Information about the resveratrol content of food is scarce and must be viewed in the context that it may vary within the same food group. Oregon State University’s Linus Pauling Institute43 provides a chart listing the resveratrol content of certain foods (see tables below).

The fruits mentioned in the table are available, but they aren’t as easy to store in their readily available form as red wine. Still, obtaining the same doses used in clinical trials through food or beverage sources (as noted in the table) is impractical, creating a market for resveratrol supplements.

Dietary supplements (pills or liquids) are generally labeled as containing 20 to 500 mg of resveratrol per tablet or capsule, yet the composition of these products is unknown. Sometimes resveratrol is combined with vitamins and/or other ingredients.

Most supplements sold in the United States contain resveratrol extracted from the Japanese and Chinese knotweed plant, Polygonum cuspidatum, while others are made from wine or red grape extracts. Japanese knotweed also contains emodin, known to stimulate bowel activity so diarrhea is a possible side effect. Similar to grapes, the resveratrol content in the roots of the Japanese and Chinese knotweed varies from plant to plant depending on environmental factors.

As discussed, only small amounts of resveratrol are found in a normal diet. In the animal and human studies conducted thus far, the dose of resveratrol used has been much larger than any amount someone can obtain through diet alone. Resveratrol supplements may contain a dosage equivalent to hundreds of bottles of wine, but typically they contain a much smaller dose than those used in research. Most supplements contain 20 to 500 mg of resveratrol. To get a dose equivalent to that used in some animal studies, a person would have to consume 2,000 mg or more of resveratrol per day. In light of this, drug companies are working on synthetic or chemical versions of resveratrol. In these forms, however, many of the beneficial substances, such as polyphenols found in food sources, will be absent.

 An important fact to keep in mind is that the FDA doesn’t regulate resveratrol supplements so there’s no guarantee that the dosage listed on the label is the actual amount present in the capsule. Often supplements will vary in content and purity of the intended compound. Consumer Labs, an independent testing and quality control organization, analyzed nine different resveratrol supplements and reported that two had far less resveratrol than what the label stated. One supplement claimed to contain 400 mg of a “red wine grape complex” but contained only 2.2 mg of resveratrol per caplet. The recommended dosages varied from 50 mg to 1,020 mg per day.

Furthermore, the cost of supplements varies widely, and each manufacturer arbitrarily sets the suggested dosage, often without basing it on human clinical trial evidence. The promotion of resveratrol far exceeds its base of clinical research. Few human studies evaluating the potential benefits or long-term risks of resveratrol supplements have been reported. There appear to be more questions than answers regarding the effectiveness of the compound in humans.8 Until more high-quality research is available, health professionals should refrain from recommending resveratrol supplements for antiaging or disease prevention.

It’s likely that companies will develop a pharmacologic form of resveratrol and with more research, one day we may be able to offer conclusive, evidence-based dietary recommendations. Until then, we should continue to recommend clients eat a plant-based diet that’s abundant in antioxidant-rich foods such as red grapes, berries, and peanuts to help prevent chronic disease. Moderate red wine consumption also won’t hurt.

— Karen Lilyquist, PhD, RN, RD, LD, has 22 years of nutrition practice experience. Since 2006, she’s taught nutrition classes for the University of Phoenix, moderated teleconferences for the National Institute for Health Education & Training, and authored continuing education courses for Nutrition Dimension.


Dawn L. Privett, RD, LD, CLT, and Carol Ann Brannon, MS, RD, LD, contributed to this article.


Learning Objectives
After completing this continuing education activity, nutrition professionals should be better able to:

1. Evaluate the characteristics and proposed mechanism of action of resveratrol.

2. Examine the food sources of resveratrol.

3. Assess the potential benefits of resveratrol related to diabetes, cardiovascular disease, and Alzheimer’s disease.

4. Distinguish the proposed antiaging properties of resveratrol.

5. Analyze at least one problem with the current delivery system for resveratrol.


1. Resveratrol is considered which of the following?
a. A phytochemical
b. A polyphenol
c. An antioxidant
d. All of the above

2. Resveratrol is naturally found in which foods?
a. Red grapes
b. Strawberries
c. Peaches
d. Sunflower seeds

3. Sirtuins play a critical role in various body processes except:
a. gene expression.
b. metabolism.
c. insulin production.
d. aging.

4. Resveratrol has been shown to have the following effect(s):
a. antioxygenation.
b. anti-inflammatory.
c. antiatherogenic.
d. All of the above

5. Resveratrol appears to be protective against cardiovascular disease by doing which of the following regarding LDL cholesterol?
a. Blocking LDL formation
b. Preventing oxidation
c. Helping with production
d. Allowing for increased HDL production

6. Apoptosis refers to the process of:
a. free radical scavenging.
b. incomplete viral replication.
c. programmed cell death and containment of damaged cells.
d. blocking prostaglandin production.

7. Resveratrol intake may lessen which diabetes symptom?
a. Poor wound healing
b. Pain from neuropathy
c. Frequent urination
d. Hypoglycemia

8. Resveratrol intake offers neuroprotection for which condition?
a. Mild cognitive impairment
b. Depression
c. Alzheimer’s disease
d. Spina bifida

9. Emerging resveratrol research is concrete as it relates to:
a. efficacy in humans.
b. optimal dosage.
c. long-term safety.
d. None of the above

10. In light of the research surrounding resveratrol, health professionals should do which of the following?
a. Recommend resveratrol supplements for those who express interest.                      
b. Refrain from recommending resveratrol supplements for antiaging and disease prevention.
c. Discuss the health benefits of resveratrol.
d. Tell clients to avoid high-oxidant foods.


Total Resveratrol Content of Selected Foods



Total Resveratrol Content (mg)

Peanuts (raw)

1 cup (146 g)

0.01 to 0.26

Peanuts (boiled)

1 cup (180 g)

0.32 to 1.28

Peanut butter

1 cup (258 g)

0.04 to 0.13

Red grapes

1 cup (160 g)

0.24 to 1.25

Total Resveratrol Content of Wines and Grape Juice


Total Resveratrol Content (mg/L)

Total Resveratrol Content in a 5-oz Glass (mg)

White wine (Spanish)

0.05 to 1.80

0.01 to 0.27

Rosé wine (Spanish)

0.43 to 3.52

0.06 to 0.53

Red wine (Spanish)

1.92 to 12.59

0.29 to 1.89

Red wine (global)

1.98 to 7.13

0.30 to 1.07

Red grape juice (Spanish)

1.14 to 8.69

0.17 to 1.30


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