On December 20 last, I was informed by my morning Boston Globe
and by e-mails from a wine-merchant friend in Boston, a wine-aware
colleague in Winnipeg, and my brother from California of the discovery
of "the key component in red wine that explains the so-called
French Paradox." An Associated Press report of a new scientific
paper was the basis of this flurry, and was the subject of a subsequent
Globe editorial on Christmas Day. Such excitement!
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 atherosclerosisthe 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
vines 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 winequercetin, resveratrol,
the catechins, and othersare 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 whats 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
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