- Resveratrol is a potent antioxidant that is thought to also have anti-aging, anti-cancer, and anti-inflammatory benefits
- While tests on rodents seem to confirm these benefits, large studies on humans have been inconclusive
- Resveratrol is found mostly in red grape skins, grape juice, peanuts, cocoa and a variety of berries
- Mild side effects include gastrointestinal discomfort such as nausea and diarrhea
Resveratrol is a special type of antioxidant, called a phytoalexin. It is produced in red grape skins, red grape juice, cacao beans (dark chocolates), peanuts (peanut butter), Japanese knotweed, blueberries, a variety of other berries, and some other plants. In plant life, it is naturally synthesized and serves as powerful protection against stress, fungal infection, injury, drought, and the sun’s ultraviolet radiation. Resveratrol supplementation was found to promote longevity in various laboratory studies that involved living creatures ranging from insects to mammals.
Because grape skins are removed early during the production process of white and rosé wines, these non-red wines generally contain less resveratrol than red wines. And because resveratrol is only a minor compound in the complete set of grape and wine polyphenols, its content in wine is usually low, highly variable, and unpredictable. Red wine thus contains small amounts of resveratrol, about 1 to 2 mg in 8 ounces of wine.
Extracts of Japanese knotweed are used in the majority of resveratrol supplements since this plant has one of the highest concentrations of resveratrol found in nature. Resveratrol is also available in solution form and as a transdermal patch, although its safety and efficacy have not been approved by the Food and Drug Administration (FDA).
The French Paradox:
Among the often-repeated arguments in support of the benefits ascribed to it, resveratrol is cited as evidence why French people who eat considerable amounts of meat, and for whom red wine is the preferred alcoholic beverage, nevertheless have fewer heart attacks and live longer on average than others in equally developed nations who drink less red wine.
Many controversial studies, mostly in cellular and animal environments, have been conducted over the past two decades or so to determine the precise effects that red wine has on us humans. In some of the most debated conclusions, the researchers thought that resveratrol has all of anti-aging, anti-inflammatory, anti-cancer, and anti-platelet benefits. More specifically, Resveratrol has been studied extensively for possibly retarding age-related human diseases and improving the impact of metabolic disorders associated with the aging process.
For its anti-cancer effects, it is thought that:
- Resveratrol blocks the spread of cancer cells while enabling malignant cells to get into their elimination sequence that results from DNA damage.
- Resveratrol blocks a certain group of enzymes that support the cancerous cells from affecting deeper tissues.
- By blocking some of the enzymes needed for the launching of certain cancer-generating chemicals, Resveratrol can inhibit the return of these chemicals to their active forms.
- Resveratrol also blocks the development of new blood vessels, a needed element in cancer growth.
Other benefits of resveratrol can be listed as follows:
- When taken orally, resveratrol is well absorbed by humans.
- Preliminary research also suggests that resveratrol may help to protect blood vessel walls against oxidation, promoting heart and vascular health.
- Resveratrol also promotes a healthy inflammatory response in the body, including helping to alleviate some of the oxidative stress and inflammation that can lead to premature aging.
- By protecting the endothelial lining of the arteries, resveratrol is thought to stimulate healthy blood flow through the arteries while supporting levels of “good cholesterol” (HDL) and proper blood pressure control.
- Most of resveratrol’s benefits concentrate on its influence on certain enzymes that generate and propel chemical reactions, thus playing critical roles on overall health and longer living; they facilitate DNA repair, reduce inflammation, and delay oxidative stress (the negative thrust of free radicals.
- In a 2006 breakthrough study, the mice that were given a high-fat, high-calorie diet plus resveratrol supplementation lived roughly 30 percent longer than a control group. They also showed far fewer age-related health problems. And although all the mice that were on this rich diet got fat, those that were given resveratrol had improved less fatty deposits in the arteries and liver and less inflammation. Supplementation with resveratrol thus actually worked against the negative impact of a poor diet, obesity, and aging.
- In one of the more renowned studies, post-menopausal women and overweight, hypertensive men, researchers observed resveratrol’s effect on the major artery of the upper arm (the brachial artery) in which blood flow can reflect on obesity and high blood pressure. After ingesting a highly bioactive form of resveratrol, participants demonstrated a prompt and significant increase of blood flow.
- In its support of heart activities, resveratrol first protects the delicate inner layer of the arteries against oxidative stress (aka “scavenging” free radicals), and then it helps to protect the production of the critical chemical, nitric acid, that keeps blood vessels optimally dilated.
While researchers who ran laboratory tests on rodents advise that resveratrol may enjoy various benefits, studies on humans remain limited and inconclusive. In mice, the benefits that were uncovered include:
- Weight loss
- Reduction in insulin resistance
- Reduction in diabetes-related death
- Anti-cancer effects
And while a 2011 limited study that was published in Cell Metabolism revealed showed no adverse reactions to resveratrol, it did reveal on the positive side that 150 mg of resveratrol once daily for a month lowered:
- Blood pressure
- Blood sugar and insulin concentrations
- And some triglyceride concentrations
Still, like various other research efforts, the researchers in this case repeated the oft-cited adage that more research with large participation will be needed before irrefutable conclusions can be arrived at.
The indications are mixed as to the effect of resveratrol on the brain, memory, cognitive function, and the elderly with Alzheimer’s and other types of dementia.
For example, while a randomized controlled trial of Alzheimer’s patients after 12 months of being on high dosage resveratrol supplementation had an encouraging though statistically almost insignificant impact on the patients’ ability to perform activities of daily living (ADLs), it had no effect on several other measures of cognition and function.
The effects of resveratrol on the brain came out also contradictory, with both benefits and damage. While patients given a supplement of concentrated resveratrol displayed a slower development of beta-amyloid plaques, there was also evidence of faster loss of brain volume, as per a brain scan. This negative effect was explained as resulting from a reduction in inflammation, although it is more commonly associated with degeneration.
Resveratrol may cause damage from hazardous interactions with frequently used drugs including blood thinners, anti-inflammatory medications, and anti-hypertensive medications.
Numerous small experimental efforts resulted in no serious side effects for dosages of daily resveratrol between 20 mg and 2 g. In one such clinical trial of Alzheimer’s patients, 12 months of taking resveratrol beginning at 500 mg and increasing to 2 daily grams was shown to be well tolerated with no adverse side effects. There are however no reliable clinical results associated with the long-term ingesting of such high doses by patients with Alzheimer’s or other types of dementia.
Karen and the Alzheimer’s clinical trial
Karen’s grandmother had Alzheimer’s for a long time, and her own mother as well died from respiratory complications arising from advanced Alzheimer’s disease. Karen thus lived most of her adult life believing that, other health issues being equal, she had a higher than average chance of developing the dreadful Alzheimer’s, or some other just-as-awful form of dementia.
One day, she heard of a clinical trial being conducted by one of the large pharmaceutical companies involving concentrated dosages of resveratrol. Their advertising emphasized the highly experimental nature of the study, disclosing the list of risks involved and other matters that Karen felt certain had been imposed on the pharmaceutic company by the Food and Drug Administration (FDA), as was their custom. Nevertheless, their message encouraged individuals with high risk of developing Alzheimer’s to apply, and it highlighted that all costs of treatment for at least 12 months would be borne by them, including out-of-pockets expenses. After first consulting with her primary care physician, a social friend of the family as well, she decided to apply and perhaps participate. She didn’t think she had a high chance of being accepted for the trial since, after all, she had no memory issues and was still with her cognitive faculties intact. At this point in her life, Alzheimer’s was all in her fearful mind.
About six weeks later, Karen received a letter advising her that she’d been accepted. The letter also instructed her as to where to go and what to do. She later discovered that she’d been accepted for her genetic disposition to dementia or Alzheimer’s, as had many of the other 135 eventual participants.
“It’s not only about what I might myself do to avert Alzheimer’s,” she confided to her best friend, “it’s also about hopefully making some progress in finding cures for the horrid disease for the entire world.”
Because old age represented the highest risk for contracting Alzheimer’s, the study aimed to corroborate the belief that most age-related diseases, including cognitive dementia, can be averted or pushed back by long-term limits on intake of calories, i.e. consuming less food on a daily basis. This had already been demonstrated in experiments on lab animals, and the hope was that similar outcomes could be shown on humans. Clinicians thus studied resveratrol because it stimulates proteins called sirtuins, the same proteins activated by lower consumption of calories.
At the end of the long and at times cumbersome trials, during which Karen was given high daily doses of resveratrol supplementation while another group was given placebo, i.e. an ineffectual substance, she had tolerated resveratrol well, while losing a noticeable amount of weight, which was quite fine by her. Some participants experienced weight loss and gastrointestinal effects such as nausea and diarrhea, while the placebo group gained weight.
What researchers found confusing was that brain MRI scans revealed that the people on resveratrol lost more brain volume than those on placebo. They postulated that the resveratrol concentrations had reduced inflammation or brain swelling found with Alzheimer’s. All in all, it was decided, unceremoniously, that more research into such effects were needed.
We humans naturally have a history spanning several thousand years of drinking wine, and enjoying grapes and peanuts without any noticeable side effects, apart perhaps from those of drinking too much wine, which is another story altogether. In animal toxicity tests, resveratrol has shown that it is also safe, even in concentrated supplements with very elevated dosages.
Always consult with your healthcare professional if sudden and unaccustomed physical or behavioral signs or symptoms crop up as a result of taking resveratrol supplements.
Resveratrol and blood thinners:
Resveratrol is an anticoagulant, meaning that it can increase the risk of bleeding during and after surgery. Resveratrol may also interact in the same way with the common blood thinner Coumadin and nonsteroidal anti-inflammatory medications such as Aspirin and ibuprofen. Avoid ingesting resveratrol products for two weeks prior to surgery, and be sure to let your surgeon know that you had been taking resveratrol.
In addition, patients who have blood disorders of the type that may cause bleeding should check with their primary health care provider at the slightest sign of unusual bleeding or excessive bruising.
Resveratrol and children:
Resveratrol supplements should not be given to children under the age of 18 unless prescribed by a doctor, for there have been no conclusive research on the subject.
Resveratrol and pregnancy:
Resveratrol reduces the activity of enzymes involved with drug metabolism but whether it has a significant effect in humans has not been studied. Avoid taking supplements of resveratrol or excessive amounts of natural foods containing resveratrol while pregnant or breast-feeding. There is a lack of research in this area as well to prove resveratrol’s safety under those conditions.
Untested anti-aging blends:
Beware of the hundreds of “resveratrol blends” that jam your grocery store’s vitamin and supplement shelves for, as you probably already know, large numbers of products have invaded this highly lucrative space, and many of these products have not been tested for effectiveness, toxicity, or other injurious interactions. In addition, many of the side effects experienced as a result of using such supplements may come not from the resveratrol, but from the other ingredients used.
Infrequent as they are, some discomforting gastrointestinal side effects have been documented for people consuming resveratrol. These include:
- Stomach upset
- Decreased appetite (only with large doses)
- Light headedness
Resveratrol and emodin:
It is also a good idea to stay clear of the purgative resin emodin, for many of the gastrointestinal discomforts and side effects come from the emodin found in some resveratrol supplements. When resveratrol extracts are made out Japanese knotweed, they commonly contain a high percentage of emodin, and the way to ensure that you are not taking emodin is to use supplements made only of 99% pure trans-resveratrol.
Joint and arthritic pain:
The Life Extension Foundation has corroborated evidence showing that resveratrol exerts natural anti-inflammatory effects. By blocking certain enzymes that cause cellular inflammation, resveratrol should in principle therefore help with conditions such as osteoarthritis in general ad joint pain in particular. Some reports of joint and Achilles tendon pain, as well as tendinitis, have however been documented in people taking resveratrol. Some tingling or numbness in the extremities have also been reported.
Resveratrol and acne:
Many supplements and drugs can cause acne, and Resveratrol is one of them, but only if you are taking a concentrated supplement. You may also witness that your acne will dissipate in time and may disappear altogether as your body adjusts.
Resveratrol and estrogenic Effects:
Resveratrol’s estrogenic activity in the body has not yet adequately analyzed for the full extent of its potential side effects. Until that is done, women with various types of cancer and other estrogen-sensitive conditions do well to allow their doctors to counsel them in that regard.
Resveratrol also performs like estrogen in the body; resveratrol supplementation is therefore not recommended for men and women who have a family history of cancer, because estrogen can intensify estrogen-dependent tumors in both breast and prostate cancer.
Resveratrol has been known to cause a general feeling of being fatigued or under the weather, as when a person has muscle aches and cramps, or with other flu-like or allergy-caused discomfort. You should consult with your healthcare professional if such feelings don’t dissipate after a few days, for they could be symptoms of something more serious.
We humans have for thousands of years enjoyed wines of all colors, grapes, nuts, and fruit (and dark chocolate) from the coca tree, hardly ever complaining of adverse reactions, except of course when we ate or drank in excess.
Then the “French Paradox” came along, confounding us endlessly. How, we ask ourselves, can the French, who smoke and eat fatty meats relatively more so than people in other advanced nations, nevertheless have fewer heart attacks and live longer? It was therefore natural to assume that it was their abundant red wine drinking that did the trick for them.
And so, we rushed to have a never-ending string of clinical studies to confirm the notion that the resveratrol that is contained in relative abundance in red wine would yield the same benefits for us humans. And while we derived some good evidence out of research conducted on flies and rodents, the jury is definitely still out, specifically in the context of giving us a response to the following question: “Can a high dose of resveratrol, consumed from supplements, result in the same conclusions?”
Regrettably, the answer so far seems to have been a “not yet”. So, on we plod with more studies, hoping that one day we might get definitive findings as to the benefits of resveratrol on the human race.