Is it the alcohol or polyphenols in red wine that decreases cardiovascular disease?

Observational epidemiologic studies relating wine and alcohol to health all suffer from the fact that they, of necessity, compare people who prefer certain beverages, but not the beverages themselves. While there have been many intervention trials in animals, randomized trials in humans are less common. Randomized crossover trials, in which each subject receives all interventions in sequence, can be especially important as they tend to avoid baseline differences among subjects and can detect effects of different interventions with smaller numbers of subjects.

This study by Chiva-Blanch G et al, just published in the American Journal of Clinical Nutrition, included 67 male volunteers in Spain who were considered to be at "high-risk" of cardiovascular disease on the basis of increased BMI, smoking, diabetes, hypertension, or other risk factors. About one half of the individuals were taking ACE inhibitors, statins, aspirin, and/or oral hypoglycemic drugs, so the results of this study may be especially relevant for patients in the real world.

The subjects agreed to not consume any alcohol for a baseline period, then for three one-month periods consumed 30 g/day of alcohol as red wine or as gin, or an equivalent amount of phenolics from dealcoholized red wine. The polyphenol contents of the RW and the DRW interventions were the same. A very high degree of compliance of the subjects with the assigned interventions is evidenced by results of counting numbers of empty bottles of the intervention beverage returned, dietary records, urinary metabolites, etc. Further, there is good evidence that there were no important changes between periods in diet or exercise habits. The effects of each intervention on a large number of adhesion molecules and chemokines that affect inflammation and relate to the development of vascular disease were evaluated.

The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that "the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease."

Specific comments on the study: Most reviewers considered this to be a well-done, comprehensive study. As one reviewer commented: "This is an excellent paper. The results strongly indicate an effect of wine polyphenols on inflammation (in broad and modern terms) and this is just what we expect from the biochemistry and nutritional effects of fruits and vegetables. The effect of ethanol, on the other hand, likely fits a hormetic mechanism, where low doses regularly supplied are protective while high doses in a single shot are worsening the progression of disease." Another reviewer added: "We need more information on separating the effects of beer, wine, and various types of spirits. Some spirits like brandy and whisky can have useful antioxidant effects, so distinguishing effects among different types of beverages may be informative."