Separating the science from MOG: Resveratrol supplements

Nutritional supplements are being investigated for prevention and treatment of various diseases and for their anti-aging potential. Resveratrol is a plant phenol found in grape, peanut, and berry varieties. It was first isolated from the roots of hellebore (Veratrum grandiflorum O. Loes) in 1940. The interest in this compound expanded when it was detected in wine in 1992. Resveratrol has been the focus of many basic science research labs and media reports. Unfortunately, research findings have not been translated into clinical practice, i.e., results using animal models and cells in test tubes have not been replicated in human subjects. Nonetheless, an over-the-counter market has developed that peddles resveratrol supplements (pills, capsules, and creams) for the following maladies:

Increase in: fat loss; ability to gain lean muscle mass; metabolism

Modulates inflammation

Prevention of cellular damage caused by free radicals; retinopathy; kidney disease; heart disease; heart attacks; stroke; development and spread of cancer cells, onset of Alzheimer’s

Prevention and Treatment of obesity and diabetes

Reduction in risk of developing blood clots

Support of the immune and autoimmune systems in fighting off disease

Alleviation of pain and discomfort due to arthritis

Resveratrol supplements are also touted to make one feel younger and stronger from its antioxidant effect and to promote longevity through a novel gene, SIRT-1 and a mechanism of action involving calorie restriction.

There are many problems with this:

(1) To reiterate, positive health claims attributed to resveratrol supplements are based on animal models and animal and human cells treated in test tubes, not human trials.

(2) The effect of moderate ethanol consumption, specifically, wine has been extensively studied on the treatment and prevention (or, decreasing the risk of) various diseases in humans.

(3) The assumption that resveratrol, separate from wine and its other constituents as well as lifestyle is responsible for the aforementioned benefits is flawed. For example, in a recently published study, Mikstacka et al. showed in test tube human red blood cells that resveratrol acted synergistically with quercetin or pterostilbene to inhibit the oxidative injury of membrane lipids, a protective effect against cardiovascular disease. (Read their abstract on our website.).

(4) Current issues with nutritional supplements use in cancer treatment include insufficient or conflicting evidence, poor quality control, potential interactions with chemotherapy, and potential efficacy in relation to changes in certain biomarkers, but long-term implications remain largely unresolved

(5) Over-the-counter nutritional supplements or complementary alternative medicines are unregulated. They often contain varying and non-reproducible amounts of active ingredients, often without detailed specifications. Thus, it is difficult to derive a recommended daily dose, and the reliability of these products is rather low.

(6) bioavailability, metabolism, dose/response and toxicity have not been well established yet

What we know:

Resveratrol is found in high concentration in red wines. That is because resveratrol is concentrated in grape skins and seeds and red wine is fermented with its grape skins and seeds. In general, white wine is not. Red wines made from grapes grown in hot, humid climates that encourage plant diseases contain the highest levels of resveratrol. For example, infection of wine grapes by the fungus Botrytis cinerea causes the so-called bunch rot or gray mold and induces the production of resveratrol in the grape. The wine made from these infected grapes, e.g. Sauternes may have a higher content of resveratrol. However, a viticultural practice like the use of fungicides during plant growth often eradicates resveratrol biosynthesis.

Resveratrol has been extensively studied in animal models and human cells in the lab and been shown to:

(1) act as an antioxidant

(2) positively regulate many physiological and cellular processes in animals by inhibiting lipid peroxidation, reducing cholesterol levels, downregulating platelet aggregation and exhibiting anti-inflammatory activity

(3) have strong chemopreventive activity against cancers

(4) have the potential to enhance longevity in yeast, worms, fish, and mice

Conclusion:

Although basic science research has shown that resveratrol, as an isolated compound separate from its red wine constituents has shown benefits in prevention of cardiovascular diseases and cancers, and promotion of longevity in several animal systems, this has not been replicated in clinical trials involving people. Any claims that resveratrol supplements have any positive effects on human health are unfounded. Remember, placebo effect is 35%!

Dennis T, Fanous M, Mousa S. Natural products for chemopreventive and adjunctive therapy in oncologic disease. Nutr Cancer. 2009;61(5):587-97.

Reiter E, Beck V, Medjakovic S, Mueller M, Jungbauer A. Comparison of hormonal activity of isoflavone-containing supplements used to treat menopausal complaints. Menopause. 2009 Sep-Oct;16(5):1049-60.

Halls C, Yu O. Potential for metabolic engineering of resveratrol biosynthesis. Trends Biotechnol. 2008 Feb;26(2):77-81. Epub 2008 Jan 11.

Espín JC, García-Conesa MT, Tomás-Barberán FA. Nutraceuticals: facts and fiction. Phytochemistry. 2007 Nov-Dec;68(22-24):2986-3008. Epub 2007 Oct 31.

Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant Effect of trans-Resveratrol, Pterostilbene, Quercetin and Their Combinations in Human Erythrocytes In Vitro. Plant Foods Hum Nutr. 2010 Jan 27. [Epub ahead of print]