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.