Resveratrol(3,5,4'-trihydroxy-trans-stilbene), a natural polyphenolic compound produced by plants, is found in the skin of red grapes and in other fruits, and it can also be produced by chemical synthesis. Resveratrol’s benefits are the subject of numerous animal and human studies. Animal studies have shown anti-inflammatory, anti-cancer, anti-aggregatory, hypoglycemic and other beneficial cardiovascular effects have been reported, as has blood pressure reduction. In humans, its effects, while generally positive, have yet to be well established.

A recent controversy cast doubt on the true efficacy of this product.  In January, reports surfaced suggesting the publication of falsified data¹.  Even, if proven true, however, the debate is unlikely to affect resveratrol research itself, because new studies support its role in improving health and wellness.

Timmers et al. investigated the intake of resveratrol on metabolic parameters and biomarkers of general health². The study consisted of 11 overall healthy but obese men with an average age of 52 years and body fat percentage of 26%. The men were administered either a placebo or 150mg/day of resveratrol in a double blinded cross study for 30 days.

The metabolic changes observed in the men using resveratrol mimicked those typically seen in individuals following the consumption of calorie-restricted diets; in particular, sleeping and metabolic rates were reduced. Resveratrol supplementation activated muscular adenosine monophosphate activated protein kinase (AMPK), which plays a role in cellular energy homeostasis.AMPK stimulates fatty acid oxidation, inhibits cholesterol and triglyceride synthesis, and enhances muscle cell glucose uptake. These changes were clinically significant, as shown by reductions in serum glucose and triglycerides, as well as improvement in the Homeostasis Model assessment index (the HOMA provides an indication of beta cell function and insulin sensitivity). Resveratrol supplementation induced metabolic changes in these obese men that were similar to the effects of calorie restriction, yet with no calorie reductions.

Most frequently associated with red wine, resveratrol is believed to be related to wine’s positive effects on cardiovascular disease.  In a recent randomized clinical trial, 67 males (average age of 60) consumed red wine (RW, 30g alcohol/d), the equivalent amount of dealcoholized red wine, or gin (30g alcohol/d) for four weeks³.  Alcohol resulted in an increase in the anti-inflammatory compound IL-10 and a decrease in macrophage-derived chemokine concentrations, a pro-inflammatory protein. The phenolic compounds present in RW reduced levels of inflammatory leukocyte adhesion molecules, E-selectin, and IL-6 and inhibited the expression of a number of constituents involved in several inflammatory pathways. The authors concluded that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both alcohol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients.

Ghanim et al. provided evidence that resveratrol reduced inflammation and oxidative stress in a controlled clinical trial with healthy individuals⁴: 20 subjects received 40mg/day of an extract containing resveratrol for six weeks. The reduction in inflammation and oxidative stress was evidenced by a reduction of serum reactive oxygen species, cytokine signalling in mononuclear cells, TNF-alpha, IL-6, and C-reactive protein.There was no change in these indices in the control group given placebo.

The effect of resveratrolon insulin sensitivity in type 2 diabetic patients has recently been investigated⁵: 19 patients (average age of 55 and a HbA1_c of approximately 7.5%) were enrolled. HbA1c (or HbA1) provides a longer-term assessment (generally over a period of 8-12 weeks) of whether blood glucose is under control. The more glucose in the blood, the more haemoglobin A1C or HbA1C will be present in the blood.A normal non-diabetic HbA1C is 3.5-5.5%. In diabetes, about 6.5% is considered under good control; thus, the patients in this study had abnormally high blood glucose.

The treatment group received two doses of 5mg of resveratrol a day or a placebo for four weeks. The resveratrol supplementation decreasedinsulin resistance (as measured by HOMA) and oxidative stress (measured bylevels ofurinary ortho-tyrosine excretion).Resveratrol treatment, though, had no effect on parameters that relate to β-cell function. This research showed that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling.

Research to date in humans suggests resveratrol improves cardiovascular health by: (1) the inhibition of vascular cell adhesion molecule expression; (2) the inhibition of vascular smooth muscle cell proliferation;(3) the inhibition of platelet aggregation; and (4) the inhibition of oxidative stress. Studies have also shown resveratrol to have anti-diabetic effects by moderating insulin activity and lower blood glucose.

Emerging research suggests resveratrol may also be effective in cancer prevention, protecting the brain from damage, reducing age-related diseases such as inflammation, and obesity.  Controversy aside, interest in the health-promoting and disease risk reduction properties of resveratrol is strong and growing.

 

References

¹Wade, N. “University Suspects Fraud by a Researcher Who Studied Red Wine.” New York Times. January 11, 2012. http://www.nytimes.com/2012/01/12/science/fraud-charges-for-dipak-k-das-a-university-of-connecticut-researcher.html

² Timmers S., E. Konings, L. Bilet, et al. 2012. “Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans.” Nitric Oxide. Jan 4. [Epub ahead of print]

³ Blanc-Chiva G., M. Urpi-Sarda, R. Llorach, et al. 2012. “Differential Effects of Polyphenols and Alcohol of Red Wine on the Expression of Adhesion Molecules and Inflammatory Cytokines Related to Atherosclerosis: A Randomized Clinical Trial.” Am J Clin Nutr.;95(2):326-34. Epub 2011 Dec 28.

⁴ Ghanim H., C.L. Sia, S. Abuaysheh, et al. 2010. “An Antiinflammatory and Reactive Oxygen Species Suppressive Effects of an Extract of Polygonum Cuspidatum Containing Resveratrol.” J Clin Endocrinol Metab. 95(9):E1-8. Epub 2010 Jun 9.

⁵ Brasnyó P., G.A. Molnár, M. Mohás, et al. 2011. “Resveratrol Improves Insulin Sensitivity, Reduces Oxidative Stress and Activates the Akt Pathway In Type 2 Diabetic Patients.”Br J Nutr. 106(3):383-9. Epub 2011 Mar 9.