You recall the French paradox. It demonstrated the association of red-wine consumption with reduction in death from heart attacks. Indolent, chubby, middle-aged and elderly Frenchmen, Gauloises ever dangling, nibbling on foie gras or Camembert, are less afflicted with coronary disease than exercising, lean, non-smoking Americans, because of the French habit of daily drinking of vin rouge.

The research group at the William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, found that red wines strongly inhibit the production in blood vessels of endothelin-1, a compound they characterize as crucial to the development of coronary heart disease, atherosclerosis. The researchers, led by Roger Corder, published their work in the highly respected journal of science, Nature, 20/27 December 2001. They noted that endothelin-1, a peptide (sort of a small protein), is a highly potent constrictor of blood vessels (narrowing them and thereby strangling blood flow), and that its overproduction is a key factor in the development of atherosclerosis. They recall that endothelin antagonists in experimental models prevented early signs of arterial disease, such as endothelial dysfunction and fatty deposition, and reduced heart attacks in those with established disease. (The endothelium, the normally smooth inner lining of the intima, the innermost layer of blood vessel walls, is the target of things going wrong in atherosclerosis–the site of clogging fatty deposits.) They point out that the blood supply to the heart muscle of patients with coronary heart disease is "severely perturbed by local endothelin-1 production." Endothelin-1 is also implicated in pulmonary arterial hypertension, an uncommon and debilitating disease (Rubin, et al., The New England Journal of Medicine, March 21, 2002).Extracts of 23 red wines, four whites, one rosé made from cabernet sauvignon, and one red grape juice, were tested on cultured bovine arterial endothelial cells. The polyphenolic extracts of red wine, even in very small quantity, strongly inhibited production of endothelin-1. Red grape juice also had some effect, but was markedly less potent. Neither the rosé nor the white wines had any effect. The strength of inhibition by the wines was proportional to their concentrations of polyphenols.

Polyphenols, many of which are flavonoids, are well known to wine drinkers and to winemakers, who often refer to them as "phenolics." They constitute, among other known and unknown compounds, the vine’s antifungal defence, and colorants, tannins, and various flavourings of wine. Those in wine are largely derived from the skins of the grapes.

The now-familiar antioxidants of wine–quercetin, resveratrol, the catechins, and others–are also polyphenols from grape skins, but, according to the Corder group, they do not inhibit production of endothelin-1. They have, however, been repeatedly demonstrated to possess properties that benefit the heart and blood vessels, as we have discussed in these commentaries.

The London group appears to believe that the cardiovascular benefits associated with red wine in particular, including decrease in heart attacks, strokes, and deaths, and lowering of blood pressure, are in major part mediated by inhibition of endothelin. This position seems to me premature, and an overreach.

Well-established research has informed us that both the alcohol in wine and its antioxidant polyphenols enhance cardiac health and longevity by increasing HDLs ("good cholesterol"), reducing and preventing noxious oxidation of LDLs ("bad cholesterol") that leads to maximal damage, inhibiting excessive blood clotting, relaxing and preventing overgrowth of muscle fibers within the walls of arteries, and promoting the health of the endothelium (perhaps via production of nitric oxide, emerging as a vital player). Some have doubted the role of the polyphenols, emphasizing only alcohol, but they are in the small minority. Pertinent is the study published by Masayoshi Hashimoto, et al., in The American Journal of Cardiology of December 15, 2001, which demonstrated that endothelium-dependent relaxation of arteries, and improvement of blood flow, resulted from intake of either red wine or red wine without alcohol. This supports the notion that constituents of wine other than alcohol improve endothelial function.

Because the skins are separated before fermentation of almost all white wines, and removed promptly in rosé production, polyphenol concentrations in such wines are low. As demonstrated by Bianca Fuhrman, et al., (Journal of Agricultural and Food Chemistry, July, 2001), in Haifa, skin contact in the presence of alcohol (and possibly the heat of fermentation) results in white wines rich in polyphenols, but not necessarily in palatable wines. The weak effect of red grape juice, made on the skins, versus endothelin likely reflects the lack of something essential from the vinification process, as speculated by Corder, et al. I suspect that at least part of what’s operative during fermentation, making wine more effective than grape juice, is alcohol.

The reports in the daily press about inhibition of endothelin-1 production by a polyphenol of red wine were flawed. They referred to the inhibitor as a pigment, and claimed it inhibits fat, but the polyphenol with which the Londoners worked was not presented as a pigment. It inhibits the production of a blood-vessel constrictor, not fat. Some press reports championed Cabernet Sauvignon as especially rich in this newly discovered panacea because four of the six highest-scoring wines were wholly or partially constituted of Cabernet, but they neglected to mention that some of the lowest scorers were also Cabernet Sauvignon: of the 23 tested red wines, three of the five lowest-scoring wines were all or substantially Cabernet.

How important are endothelin-1 and the reported inhibition of its production? Highly intriguing and possibly of great value, but this is one small study needing confirmation and elaboration, so hedge your bets. One of the first things we need to know is whether the endothelin-inhibiting polyphenol is absorbed into the body from the wine we drink. Else, it is of little interest. (I suspect that, like antioxidant polyphenols, it is absorbed.) It would also be convenient to isolate the little devil, so that we could name it.Might we be looking at the "key component in red wine that explains" the French paradox? . I feel certain we are not, for, as partially recounted above, the salutary cardiovascular effects of moderate wine consumption are complex and still unfolding. It will be necessary to make certain that both endothelin-1 and the polyphenolic inhibitor of its production are major players, by no means irrefutably established, and then to integrate their actions into our understanding of the formation of and protection from atherosclerotic disease of the coronaries and other arteries.

*Dr. Harvey E. Finkel, an award-winning wine writer, is clinical professor of medicine at the Boston University Medical Center. He writes and lectures internationally on the influences of wine upon health, and is a member of AIM ‘s editorial board