Resveratrol Improves Cardiovascular Health in Obese Adults: The First Evidence Using Oral Administration in a Clinical Trial Setting

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It is well documented that red wine harbors many health benefits; including, but not limited to, cardiovascular improvements.  Research has shown that it is likely the polyphenols in the skins of grapes that provide these health benefits.  The Academic Wino has presented several studies demonstrating the health benefits of wine, including Champagne’s cardiovascular health benefits, red wine’s role in decreasing incidence of dementia, and the role of grape pomace in decreasing the symptoms of diabetes.

Using self-reported surveys, studies have found that red wine consumption is associated with a lower risk of obesity and weight gain, compared to other alcoholic beverages (beer and spirits) that show the opposite effect.  Some cardiovascular risk factors, such as hypertension and obesity, are associated with impaired flow-mediated dilation (FMD), which is characterized by a loss of endothelium-dependent vascular smooth muscle relaxation (i.e. poor cardiovascular health).  Scientists speculate that this impairment is due to reductions in endothelium-derived NO (nitric oxide) availability, which may play an important role in the progression of cardiovascular disease.

Many studies have found that foods rich in polyphenols result in improvements in FMD in those groups that are at high-risk for cardiovascular disease (ex., peanuts, cranberries, mulberries, red grapes/wine, green tea, and dark chocolate).  Specifically, resveratrol (3,5,4’-trihydroxystilbene), a polyphenols that is found in the skins of grapes (and the resulting red wine), has been tied to cardiovascular improvements in vivo.  The concentration of resveratrol varies, depending upon the variety of grape and the winemaking processes used, and is reported to be between 0.1 and 14.0mg/L.  In the United States, it is estimated that the daily intake of resveratrol (from naturally occurring sources) is 0.08mg, with the 90^th percentile consuming up to 0.26mg daily.

There has been a wide breadth of research focusing on the health benefits of resveratrol, and studies have found these benefits include defense against ischaemic-reperfusion injuries (think heart attacks, stroke, or other events where there is a sudden block of blood flow), increased antioxidant levels, and increased NO bioavailability through enhanced endothelial NO synthase expression.  It the rat model, it has been shown that after daily doses of resveratrol, the progression of endothelial dysfunction was slowed, the effects of which were attributed to the reduction of vascular smooth muscle cell proliferation and the enhancement of endothelium-derived NO synthase and NO bioavailability.

Based on these studies and others that have shown evidence of resveratrols’ cardiovascular benefits, the authors of the study presented today speculate that resveratrol administration may enhance FMD in overweight/obese individuals whose FMD may be compromised.  At this point in time, there have been no human studies addressing this issue, and those studies involving humans have only been using self-reported surveys (which are often plagued by biases).  The overall objective of the study presented today, which was very recently published in the journal Nutrition, Metabolism, & Cardiovascular Diseases, was to investigate whether or not oral administration of resveratrol could improve FMD in a dose-dependent manner.

Methods

The study was a randomized, double-blind, placebo-controlled, crossover human intervention trial with four visits at weekly intervals.

The study volunteers were overweight/obese, with a BMI greater than 25kg/m² and less than 35kg/m².  Volunteers were adults between the ages of 30 and 70, with elevated blood pressure (systolic BP between 130 and160mmHg and/or diastolic BP between 85 and 100mmHg).  Female volunteers were required to be post-menopausal for at least the last 12 months.  Volunteers has no history of cardiovascular disease, diabetes, renal disease, were not taking any medication for high blood pressure or diabetes, and were non-smokers.

Volunteers were instructed to maintain their usual diet, but limit polyphenols intake and physical activity throughout the day.

Volunteers were instructed to consume three doses of resveratrol (30, 90, and 270mg) and a placebo at weekly intervals in a randomized, double-blind method.

FMD was measured via ultrasound technology and analyzed using Brachial Analyzer (an edge-detection software), according to published methods.  After FMD measurements, a blood sample was collected for resveratrol analysis.  Liquid chromatography was used to measure the concentrations of trans-resveratrol in the blood samples (“free”, “total”, and dihydroresveratrol).

Results

•       19 volunteers completed the experiment (14 males, 5 females).
•       With increasing dosages of resveratrol, there was a proportional increase in blood plasma concentrations of resveratrol.

o   There was a significant relationship between resveratrol dose and blood plasma resveratrol concentration (p2 = 0.63).

•       There was a significant linear relationship between the log₁₀ transformed blood plasma resveratrol concentration values and acute FMD (p2=0.08).
•       There were no significant differences in the baseline brachial artery diameter values before the resveratrol administration, however, once resveratrol was consumed, there was a significant linear relationship between the log10 transformed resveratrol dose and the acute FMD response (p2=0.08).

o   For each of the doses of resveratrol, FMD significantly increased compared to the placebo (p<0.05).

Discussion/Conclusions

According to the authors of this study, it is the first of its kind to investigate the acute effects of resveratrol consumption on human circulatory function.  This study was successful in showing that oral administration of resveratrol improved endothelium-dependent vasodilatation by increasing FMD with each dose of resveratrol.  Even at the lowest dose of resveratrol (30mg), FMD was significantly improved. 

Another recent study showed that NO production, which is linked to FMD, could be enhanced in blood platelet cells of healthy humans after 15 days of 300mL/day red wine consumption (side note: hmmm….must read and present this study…), the amount of resveratrol of which only measured to be 0.5μmol/L.  The authors of that study speculated that it was not just resveratrol, however, that resulted in the improved NO production, but the interaction between that and other polyphenols in the red wine.

The results of these and the current study are promising, in that it appears as though resveratrol may significantly improve cardiovascular function (in the form of FMD enhancement) in overweight/obese adult humans, however, at this point it is unclear if the amount of resveratrol normally consumed in daily diets will have the same effects.  For example, the lowest dose of resveratrol in this study (30mg), cannot be obtained from normal diets.  Therefore, if one were to consume a glass of wine daily, while it does provide many health benefits, it may not enhance FMD at the levels that were obtained in the current study.  If one were to take resveratrol supplements in pill form, results may (or may not) be similar to the results found in the study (though consult your doctor before taking this or any type of dietary supplement).

This study is the first of hopefully many that will show the positive effects of resveratrol on cardiovascular health in human subjects.  The current study was very simple, and only included a small number of study participants.  More studies with larger samples sizes are critical in examining this area further.

In general, I thought this was a very promising study, in that it seems clear that oral administration of resveratrol significantly improves that flow-mediated dilation (and thus cardiovascular health) of overweight/obese adults, and I am looking forward to the studies that emerge from this flagship research.

I’d love to hear what you all think! Please feel free to leave your comments below!

Source: Wong, R.H.X., Howe, P.R.C., Buckley, J.D., Coates, A.M., Kunz, I., and Berry, N.M. 2011. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutrition, Metabolism & Cardiovascular Diseases 21: 851-856.

DOI: 10.1016/j.numecd.2010.03.003
I am not a health professional, nor do I pretend to be. Please consult your doctor before altering your alcohol consumption habits. Do not consume alcohol if you are under the age of 21. Do not drink and drive. Enjoy responsibly!