Extensive epidemiological data generated over the past decade
has unequivocally demonstrated that the regular and moderate consumption
of alcoholic beverages per se has a cardioprotective effect, resulting
in a substantially reduced risk of death from cardiovascular disease,
with a corresponding reduced/consequent reduction in, risk of
death from all causes, including from cancer.
Evidence that alcoholic beverages are cardioprotective is strengthened
by plausible mechanisms of action. The ethanol component, for
example, increases the serum concentration of high density lipoprotein
(HDL), and consequently increases the ratio of HDL to LDL, where
a low serum concentration of HDL is associated with an increased
risk of cardiovascular disease. Ethanol also affects haemostatic
factors, coagulation and fibrinolysis, decreasing platelet aggregation
and concomitantly increasing the capacity for clot dissolution
approximately 5- 6 hours post alcohol consumption.
Wine, because it contains phenolic compounds in addition to ethanol,
may have additional cardioprotective mechanisms to beer and spirits.
The consumption of fruits and vegetables that contain phenolic
compounds and their esterified derivatives, is generally associated
with a reduced risk of cardiovascular disease. This association
is what led to the proposition that wine may have a dietary effect
similar to that of fruits and vegetables, especially as the consumption
of two 100 mL glasses of red wine per day increases the phenolic
content of the average diet by approximately 40%. Approximately
10 different classes of phenolic compounds have been isolated
from wine, and while there is no definitive data on which class
is the most efficacious concerning cardioprotection, a potential
order has been proposed whereby the phenolic acids, flavonols
such as catechin, and flavonols such as quercetin and myricetin,
may be the most efficacious classes.
From in vitro data, it has been purported that the primary cardioprotective
effect of the phenolic compounds is anti-oxidation, or the prevention
of oxidation of plasma compounds such as low density lipoprotein
(LDL). A high plasma concentration of LDL is another risk factor
for cardiovascular, where oxidized LDL aids all stages of the
atherosclerotic process. In vitro data have consistently demonstrated that under certain conditions,
the phenolic compounds increase the antioxidant capacity of plasma.
The data have also demonstrated that the specific consumption
of wine does confer protection against the oxidation of LDL by
circulating free radicals, and this protection is dose-dependent
where red wine is 10- 20-fold more protective than white wine.
The numerous in vitro data have not been completely nor convincingly supported by subsequent
in vivo data, however. Six of seven in vivo studies conducted to date have demonstrated that the wine-derived
phenolic compounds are active antioxidants; the seventh study,
however, failed to show either absorption or activity. These six
studies have also demonstrated that significant antioxidant activity
may only be observed following the medium to long-term consumption
of wine, although phenolic compounds are absorbed in significant
amount after the acute and short-term consumption of wine.
In 1996, in vitro studies undertaken by the Department of Medicine at the University
of Western Australia showed that red wine, and in particular wine-derived
phenolic acids, had significant antioxidant activity. An acute
study of 12 male subjects consuming approximately 350 mL of either
red wine, de-alcoholised wine, phenolic stripped red wine or water
over a 30 minute period with food then showed that the wine-derived
phenolic compounds are bio-available, but that such acute consumption
does not increase the antioxidant capacity of plasma.
In a subsequent short-term study, 18 male subjects consumed 375
mL of red, de-alcoholised red or white wine daily for two weeks,
with a wash-out period of one-week between each beverage. The
subjects were all cigarette smokers, chosen specifically as smoking
increases significantly oxidative damage and stress. Samples of
plasma and urine were collected and analysed for phenolic acid
compounds as biomarkers of the absorption of wine-derived phenolic
compounds per se, and for free and esterified 8-isoprostanes.
The latter are oxidation products of arachidonic acid that accumulate
in plasma and are excreted in urine, thus providing a measure
of oxidative damage and stress. It has been previously published
that the concentration of these oxidation products increases in
cigarette smokers and in the presence of ethanol, but decreases
in the presence of antioxidants in vitro and in vivo.
Similar to the initial acute study, following the consumption
of the red wine or de-alcoholised wine, the plasma and urine concentration
of the analysed phenolic acids increased significantly (P<0.001).
As anticipated, the plasma and urine concentration of the free
and esterified 8-isoprostanes decreased significantly following
the consumption of the de-alcoholised red wine, which suggests
that the antioxidative wine-derived phenolic compounds decrease
the extent of, and hence protect against, in vivo oxidative damage.The remainder of the results were, however,
unexpected. For example, the concentration of these oxidation
products did not decrease following consumption of either the
red or white wine, but remained at the baseline concentration,
which was similar for the two wines. The white wine contained
an equivalent concentration of ethanol to the red wine, but contained
approximately two thirds less phenolic compounds. These results
suggest that any antioxidant effect of the wine-derived phenolic
compounds was being countered by a pro-oxidant effect of the ethanol
component of the wine. It has been previously demonstrated that
the hepatic metabolism of ethanol induces the oxidation of lipids,
such as LDL.
There was, however, no increase the concentration of the oxidation
products, that is, no pro-oxidant effect was observed, following
consumption of the white wine. An increase in the plasma and urine
concentration of the oxidation products should have been observed
if the pro-oxidant effects of the ethanol component could not
be completely countered by the antioxidant effect of the phenolic
compounds. From previous research results, it has been suggested
ethanol increases oxidative stress and the concentration of the
free and esterified 8-isoprostanes in a dose-dependent manner.
Therefore, the moderate consumption of the white wine in this
in vivo study may have only had an insignificant pro-oxidative effect.
Any variation in the results of the now eight in vivo studies on antioxidant activity may reflect differences in study
design and duration, especially as the pro-oxidant effects of
ethanol and the anti-oxidant effect of the wine-derived phenolic
compounds may both be dose dependent, as well as differences in
the measures used to assess antioxidant activity.
This Australian in vivo study confirms the bio-availability of the wine-derived phenolic
compounds and that they are Continued on page 11 anti-oxidative in a dose-dependent manner. The anti-oxidant effects,
however may be partly or completely counteracted by the pro-oxidant
effects of ethanol concomitantly consumed. The net result may
thus be dependent on the relative concentration of ethanol and
phenolic compounds in the environment of LDL.
In conclusion, the results of these Australian studies confirm
the results of the majority of the acute and short-term studies
undertaken previously that demonstrate that wine-derived phenolic
compounds are active antioxidants. The failure, however, to demonstrate
significant antioxidant activity following the consumption of
red and white wine containing both ethanol and phenolic compounds
may mean that the wine-derived phenolic compounds may merely counteract
the pro-oxidative effects of alcohol on plasma lipids. It may
also reflect the particular population group studied, cigarette
smokers, who may have unique characteristics concerning oxidative
stress, but in order to draw such a conclusion further clinical
studies are clearly required in both cigarette and non-cigarette
smoking population groups. Such a clinical study that utilises
traditional measures of oxidative damage and stress, as well as
that of isoprostanes, is currently being undertaken. In addition,
as the true biological meaning of the different ex vivo oxidation experiments conducted remains unknown, the challenge
now is to conduct studies that use end-points more closely related
to cardiovascular disease.
Therefore, any additional cardioprotection conferred by the wine-derived
phenolic compounds may be primarily related to haemostatic factors,
where, the magnitude and significance of any additional cardioprotection
afforded by wine compared to beer and spirits is still under investigation.
References Red wine polyphenols, in the absence of alcohol, reduce lipid
peroxidative stress in smoking subjects. Abu-Amsha-Caccetta,-R
et al Free-Radic-Biol-Med. 30(6): 636-42; 2001.Ingestion of red
wine significantly increases plasma phenolic acid concentrations
but does not acutely affect ex vivo lipoprotein oxidizability.
Caccetta,-R-A et al: Am-J-Clin-Nutr. 71(1): 67-74; 2000.