Product Review: Resveratrol Supplements (Grape, Red Wine, and Polygonum Sources)
||Initial Posting: 10/8/16 Last Update: 3/14/17
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Summary: What You Need to Know About Greens and Whole Foods Powders and Pills
- Does it help? There is some preliminary evidence that resveratrol supplements may be helpful for age-related macular degeneration, however, evidence for other popularly promoted uses, such as cardiovascular health, diabetes, memory, and life-extension is quite limited, and in some cases, contradictory. (See "What It Does").
- Which form? Resveratrol is a plant chemical found in red grape skins and grape seeds, purple grape juice and red wine, but most resveratrol in supplements comes from the Japanese knotweed plant (Fallopia japonica or Polygonum cuspidatum). Resveratrol exists in either the cis- or trans- form, but trans-resveratrol is found most abundantly in nature and is the most-researched form. (See "What It Is").
- Which product? All but one of the products tested in this review were found to contain the amounts of resveratrol claimed on their labels, which ranged from 50 mg to 500 mg per serving. (See "What CL Found"). The only product which was Not Approved listed an amount of "resveratrol complex" which CL discovered to be only 11.8% resveratrol with no information about its other constituents.
- Best value? CL calculated the cost to obtain 100 mg of trans-resveratrol from each Approved product, finding this to range from just 6 cents to more than $1. Several which cost 10 cents or less per 100 mg were chosen as CL's (See Top Picks).
- Dose? Although there is no established safe and effective dose for resveratrol, a typical dose of approximately 150 mg per day may have activity in people, although higher doses are also used. (See What to Consider When Using).
- Don't get hurt! Resveratrol should not be taken by women with estrogen-sensitive conditions, nor by children, or women who are pregnant. People taking blood thinners are strongly advised to consult a physician before taking resveratrol because of potential drug interactions. (See Concerns and Cautions for more information).
What It Is:
Resveratrol is a plant chemical found in red grape skins and grape seeds, purple grape juice and red wine, and in smaller amounts in peanuts. Resveratrol is also found in other plants such as the roots of the Chinese medicinal herb, hu zhang — commonly known as Japanese knotweed (Fallopia japonica or Polygonum cuspidatum) — which is typically the source of resveratrol in supplements. Japanese knotweed originated in Japan and China, but in the late 1800's was introduced in the U.S., where it is now considered an invasive species (it tends to crowd out other plants, and its roots can damage river banks, building foundations, etc.) In Japan, young leaves and shoots of the plant are eaten; however, amounts of resveratrol found in the plant would be much lower than amounts in an extract from the plant — which would be much more highly concentrated. Resveratrol extracted from Japanese knotweed for supplements is likely to come from China, although there are other sources, such as Canada. Labels typically do not list the country of origin, but some manufacturers may be able to provide this information if you ask them. Resveratrol is also found in the roots of a South American shrub (Senna quinquangulata).
Red wine extract, red grape skin extract, grape seed extract (GSE), grape pomace extract (GPE), and Polygonum cuspidatum extract contain varying amounts of resveratrol along with other plant chemicals.
Resveratrol exists in either the cis- or trans- form. Cis- and trans-resveratrol have some common biological activities while other activities are specific to only one form or the other. Each contain the same type and number of atoms, but the orientation of the atoms is slightly different. Either form can exist as free compound or attached to a sugar as a glycoside. In nature, the trans- form is most abundant. It is also the most commercially available and the most researched.
What It Does:
Although resveratrol is found in red wine at about 1 to 2 mg of trans-resveratrol per bottle (Stervbo, Food Chem 2006), resveratrol supplementation has yet to be shown to offer the cardiovascular benefits associated with moderate alcohol consumption, such as a reduced risk of heart attack.
Some studies have shown that supplementation with resveratrol can improve endothelial function in blood vessels, but, more importantly, it has not consistently been shown to help reduce blood pressure. For example, a study found that in people with metabolic syndrome who took 100 mg of resveratrol daily for three months, flow-mediated dilation increased 5% (Fujitaka Nutr Res 2011), but there was no significant effect on blood pressure, insulin resistance, lipid profiles or inflammatory markers. A four week study in obese men found that a high dose of resveratrol (3 tablets containing 500 mg of trans-resveratrol each, for a daily total of 1,500 mg trans-resveratrol) did not have any effect on blood pressure or rates of lipid oxidation (Poulsen, Diabetes 2013).
Although one study suggested that a combination of resveratrol and grape seed extract may help lower levels of bad cholesterol and improve measures of inflammation, the researchers warned that high daily doses of resveratrol (hundreds of milligrams to grams) could inhibit enzymes important for the metabolism of statins and other drugs for cardiovascular disease (Tome-Carneiro, Ann N.Y. Acad. Sci 2013). A more recent study in Denmark among middle-aged men with metabolic syndrome found that a high daily dose (1,000 mg) of resveratrol (purity >98%) taken for four months, modestly increased total and "bad" LDL cholesterol, and worsened one measure of blood sugar (fructosamine) as compared to placebo (Kjaer, J Clin Endocrinol Metab 2017). A lower daily dose (150 mg) did not have this effect; however, neither the low nor high dose showed any other benefit (such as a reduction in blood pressure, inflammation, or body fat) in the men. The increase in cholesterol levels with the high dose appears to be consistent with findings of a laboratory study in which resveratrol was shown to increase atherosclerosis (hardening of the arteries) in animals fed a high-fat diet (Wilson, Life Sci 1996).
Be aware that resveratrol may have a blood-thinning effect, and so should not be used by people taking blood-thinning medications without physician supervision (See Cautions and Concerns).
There is conflicting evidence regarding whether or not resveratrol is beneficial for glucose control in people with diabetes.
However, a longer and larger study of 179 men and women with type 2 diabetes in Italy (average age 65), most of whom were taking oral diabetes medication such as Metformin, found that taking either 40 or 500 mg daily of resveratrol (as trans-resveratrol from Biotivia Bioceuticals) did not improve fasting glucose, hemoglobin A1c, insulin resistance, CRP (a measure of inflammation), total cholesterol, or blood pressure, compared to placebo (Bo, Pharmacol Res 2016). The researchers noted that studies which have found resveratrol to improve glucose control in diabetes (such as the one above) have tended to have involved younger participants. They theorized that resveratrol may be less helpful in people who have had diabetes for longer periods of time.
Animal research of resveratrol has demonstrated a "life-extending" effect. Specifically, in mice made obese with an extremely high fat diet, those given resveratrol lived an average of 15% longer than those not provided the supplement. The resveratrol-fed mice also showed increased insulin sensitivity and improved motor function. Whether normally fed mice also show lifespan extension by resveratrol remains unanswered. However, the current research in animals as well as people suggests that the initial excitement about resveratrol as a life-extending supplement was exaggerated, as this benefit may be limited to those with type 2 diabetes or other insulin insensitivity (often associated with obesity). Similarly, although resveratrol has been found to either directly or indirectly activate the SIRT1 gene (Hubbard, Science 2013) — sometimes referred to as the "longevity gene" and associated with cellular metabolism, cellular repair, and lifespan animals (Li, Acta Biochim Biophys Sin 2013) — more research is needed to determine the implications of this for human health.
A 30-day study of resveratrol (150 mg/day of 99% pure trans-resveratrol — resVida) in obese men showed it mimicked the metabolic effects of a calorie restricted diet (Timmers, Cell Metabolism 2011). While this did not affect the subjects' weight, the researchers suggested that the effects represented improvements in general health parameters, as the treatment caused lower systolic blood pressure, improved liver function, and significantly lower triglyceride levels. There were also indications of improved insulin sensitivity, consistent with earlier pilot studies.
One small study in Germany in overweight but healthy individuals (ages 50 to 75) found that 26 weeks of resveratrol (200 mg with 320 mg of quercetin daily -- divided into two doses taken with meals) not only improved glucose metabolism, but also improved memory performance and activity in the hippocampus, a region of the brain involved in memory function. People who received resveratrol were able to retain significantly more words 30 minutes after hearing them than those who received a placebo. On other measures of memory, such as recognition and learning ability, those receiving resveratrol also improved, but by about the same amount as those who receiving the placebo (Witte, J Neurosci 2014).
A one year study among men and women with mild to moderate Alzheimer's disease found that a biomarker (A?40) which typically decreases with progression of Alzheimer's remained stable in people given large doses of resveratrol, while it decreased in those given placebo. There were no significant effects on other biomarkers and cognitive functioning decreased in both groups — although slightly less in the resveratrol group, but this was not statistically significant. Brain volume loss was actually greater in the group receiving resveratrol, but was not associated with cognitive decline and has been seen in studies of other potential treatments. The daily dose started at 500 mg of resveratrol and increased up to 2,000 mg over the course of the study. The researchers cautioned that the findings are preliminary and do not prove resveratrol is beneficial in Alzheimer's disease; further research is required (Turner, Neurology 2015).
Some very preliminary evidence suggests resveratrol could be helpful for age-related macular degeneration (AMD). For example, one laboratory study found that resveratrol inhibited the production of vascular endothelial growth factors (VEGF) (the overexpression of which is known to worsen AMD) in human retinal cells (Nagineni, Aging Dis 2014). (VEGF is also the target of anti-VEGF drugs such as Lucentis, Eylea and Avastin, which are injected directly into the eye in order to help slow the abnormal growth of blood vessels and slow vision loss in conditions such as wet AMD). There have been a few cases of people with AMD experiencing improvement or slower progression of the disease while taking the Longevinex brand of resveratrol, each reported by the same doctor (Richer, Optometry 2009; Richer, Nutrients 2013; Richer, Nutrients 2014). Among these cases, modest improvements, such as reduction of edema and excessive blood vessel growth in the eye and increased macular pigment volume were reported when one capsule of Longevinex (providing 100 mg of trans—resveratrol from Polygonum cuspidatum, plus rice bran phytate, quercetin, chlorogenic acid, green tea extract and 1000 IU of vitamin D) was taken daily over a period of time ranging from six weeks to three years. One small study among young healthy men and women found that a single capsule of Longevinex increased choroidal thickness (which may decrease in AMD) one hour after ingestion (possibly by increasing blood flow to the eye), compared to placebo (Wang, Curr Eye Res 2016). However, there do not appear to be any randomized, placebo-controlled studies on the effects of Longevinex, or any resveratrol supplement, in people with AMD.
One small study among young healthy men and women found that a single capsule of Longevinex increased choroidal thickness (which may decrease in AMD) one hour after ingestion (possibly by increasing blood flow to the eye), compared to placebo (Wang, Curr Eye Res 2016). However, there do not appear to be any randomized, placebo-controlled studies on the effects of Longevinex, or any resveratrol supplement, in people with AMD.
Although there are a number of animal and laboratory studies on the effects of resveratrol on certain types of cancer, there is very little research on resveratrol's effects in people with cancer, or for the prevention of cancer. As noted in one review of the current evidence, "The promising neurodegenerative and cancer chemopreventive effects of RES [resveratrol] in animal models have not been yet confirmed in humans." (Tome-Carneiro, Curr Pharm Des 2013). In addition, because resveratrol has mild estrogenic activity, women with estrogen-sensitive cancer should consult a physician before using (See Concerns and Cautions).
Long-term studies are needed to confirm these findings. Many clinical trials involving resveratrol are currently underway.
For more information about dosage see the ConsumerTips™ section. Also see Concerns and Cautions.
Quality Concerns and What CL Tested for:
As no government body normally tests resveratrol supplements, ConsumerLab.com purchased and tested products to determine how much resveratrol they contained, the chemical form of the resveratrol, the amount of pterostilbene (a related compound) if listed, and whether this matched claims on the label. Products containing whole herb and/or 250 mg or more of minerals were also tested for contamination with lead, cadmium and arsenic, as these can occur in plant-based supplements. Tablet and caplet products were additionally tested for their ability to properly break apart for absorption.