Wednesday, November 2, 2011

Red wine in a pill: Metabolic effects of resveratrol in humans

Remember back in July I talked about a future where simply popping a couple of resveratrol tablets gave the same benefit as a walk around the block?  That future may be closer than we think!  A recent paper in the journal Cell Metabolism describes the results of a very small study of resveratrol in humans and the data is pretty exciting.  Let me repeat that caveat... this was a small study!  Still, the metabolic effects described in this work clearly emphasize the need for further research on this and other magical polyphenols.

The paper published by Timmers et al. (abstract) is the first to study the metabolic effects of resveratrol (RES) in a clinical setting.  Eleven obese men were given either RES (at 150mg/day) or placebo for 4weeks, followed by a 4-week washout and then the treatment was switched (this is known as a crossover study).  Patients and doctors were both blind as to what treatment was being administered and during treatment, a variety of metabolic tests were conducted.  There is a lot of data in the paper (and it looks like the pdf is free, so check it out yourself!) but let me hit a few highlights:

1) Patients taking RES show an increase in mitrochondrial efficiency, particularly in fatty acid oxidation of muscle fats, and decreased levels of triglycerides and glucose levels.  Significantly, these changes are seen at the gene level, suggesting that it is the overall metabolic pathway that is improved, not just a downstream clearance of metabolic markers.  A similar pattern of changes has been noted in athletes undergoing endurance training (they reference Dube et al, 2008 and Meex et al, 2010).  This is fairly consistent with the Momken paper I blogged about back in July, ie, RES acts like an exercise mimetic.

2) Changes in glucose and insulin levels are modest.  Timmers et al. report a statistically significant drop in serum glucose and insulin levels in the patients taking RES, but this effect is pretty modest.  There is also a shift in peak glucose and insulin levels after a liquid test meal, suggesting some changes in glucose homeostasis, but they could not draw definitive conclusions.  If you recall, the rat data from Momken et al. was also pretty weak with regard to insulin/glucose levels.

3) RES also showed other health benefits:  This study also demonstrated a significant effect of RES on lowering systolic blood pressure and mean arterial blood pressure, as well as decreases in resting energy expenditure and sleeping metabolic rate.  The later two effects are also seen in studies of calorie restriction and further illustrate the metabolic changes induced by RES.  Calorie restriction is also associated with increased lifespan in animals, so these observations may be pointing to another possible health benefit of RES.  They also observed a decrease in markers of inflammation, further suggesting an overall improvement in health. Although this is interesting, I still think the catechins are the more potent player here... I'd like to think that as the flavinoids polymerize during aging, the wine gets better and better for your heart. It would be interesting to see how some of these molecules perform in a study similar to this.

Taken together, this paper highlights some of the metabolic effects of RES in humans and may offer some insight into the health benefits of this polyphenol.  Much like the rat study, however, this is a very high dose (the equivalent of >100 glasses of wine per day) and so who knows if there are long term side effects at this dose.  The fact that they see statistical significance with only eleven patients is also very surprising.  Clinical studies usually need hundreds, or even thousands of patients to provide enough statistical power to draw conclusions like this.  Personally, I would find taking a pill much less satisfying that enjoying a nice glass of Cabernet. Since that glass of Cab is a veritable grab bag of Redox goodies, I think it is also very likely that there are many other 'good' polyphenols in wine that scientists haven't studied as rigorously as RES.  So as dozens of trick-or-treaters descended upon our neighborhood on Halloween night, I had to raise my glass to our ancient ancestors who discovered the wonderful winemaking process, and the scientists who now try and tease apart how it does what it does. I may have also stolen a chocolate or two... in the interests of science, you know.