Page last updated: Tuesday, March 29, 2005
An update of evidence of the specific benefits of alcohol consumption
Creina S. Stockley, Health and Regulatory Information Manager, The Australian Wine Research Institute
All alcoholic beverages have the ability to reduce the risk of death from cardiovascular disease, and even that from all-causes by between 20 to 50 percent, when consumed in moderation (St Leger et al. 1979, Boffetta and Garfinkel 1990, Marmot and Brunner 1991, Thun et al. 1997, Muntwyler et al. 1998, Hoffmeister et al. 1999, Gaziano et al. 2000). This ability to prolong life has been demonstrated by the extensive epidemiological or population studies, which have been undertaken in men and women, for different age groups, and for different nationalities or population groups.

Ethanol-derived beneficial effects

Some of these studies have also considered the alcoholic beverage consumed and the reduction in risk of, for example, cardiovascular disease, which includes high blood pressure, heart attacks and non-haemorrhagic strokes. From these studies it can be concluded that the alcohol component, which is common to all the beverage types, does confer a significant benefit. This benefit is considered to be, primarily, an increase in the plasma concentration of high density lipoprotein (HDL) cholesterol, where a low plasma concentration of HDL is correlated with a high risk of cardiovascular disease (Langer et al. 1992, Renaud et al. 1992, Suh et al. 1992, Gaziano et al. 1993, Folts et al. 1994, Hendriks et al. 1994, Ridker et al. 1994, Fielding and Fielding 1995, Renaud and Ruf 1996, Simons et al. 1996, 2000). HDL transports dietary-derived cholesterol from the arteries and body organs and tissues to the liver, where it is removed from the body or repackaged for cellular usage. In addition, alcohol decreases blood clotting by reducing the ability of the blood cells to aggregate and clot together, and also by increasing their ability to de-aggregate once blood clots have formed in arteries and veins (Renaud et al. 1992, Hendriks et al. 1994, Folts et al. 1994, Ridker et al. 1994, Renaud and Ruf 1996). Phenolic compound-derived beneficial effects

Particular epidemiological studies have indicated that consumers of wine have a greater reduction in the risk of cardiovascular disease than consumers of beer or spirits. The reduction in risk was similar to that for consumers of certain fruits, grains and vegetables, where the linkage between wine and these foodstuffs is their concentration of phenolic compounds (Grundy 1986, Block 1992, Block et al. 1992, Ames et al. 1993, Hertog et al. 1993, Kinsella et al. 1993, Willett et al. 1995, Halliwell et al. 1995, Renaud 1996).

Phenolic compounds, such as flavonols, phenolic acids and their esterified derivatives, are purported to act as antioxidants. Thus the major cardioprotective activity and mechanism currently proposed for the phenolic compounds is antioxidation, or the prevention of oxidation of certain compounds, such as low density lipoprotein (LDL), by circulating free radicals. Another risk factor for cardiovascular disease is a high plasma concentration of LDL cholesterol, in particular if the corresponding concentration of HDL is low. In its oxidised form, LDL accumulates on arterial walls and if not removed, continues to accumulate; this is referred to as atherosclerosis. As the artery narrows due to the accumulated oxidised-LDL, blood pressure increases to maintain blood flow. Eventually, blood flow may be completely blocked if the artery continues to narrow and completely occludes or if a segment of the accumulated oxidised-LDL breaks away and lodges in a smaller blood vessel. This would result in a heart attack or stroke depending on the site of the blockage.Wine-derived phenolic compounds

The wine-derived phenolic compounds are located in the skins and seeds of grapes and during fermentation they are extracted into the juice. The concentration of phenolic compounds in wine is significantly greater than that in the majority of other foodstuffs, and their concentration is six-fold greater in red than that in white wine (de Whalley et al. 1990, Frankel et al. 1995, Hertog et al. 1995, Croft et al. 1996, Kerry and Abbey 1997). This difference also correlates with the difference in antioxidant capacity between red and white wine, and reflects the colour or pigment difference between red and white grapes, and hence wine. In addition, there are differences in the concentration of phenolic compounds between the varieties of red and white grapes, and viticultural and winemaking factors also influence and contribute to the concentration of phenolic compounds in the final or finished wine (Singleton 1982, Ramey et al. 1986, Kovac et al. 1992, Seimann and Creasy 1992, Singleton and Trousdale 1992, Price et al. 1995, McMurtrey 1997, Revilla et al. 1997, Soleas et al. 1997a, 1997b). Most of the earlier evidence of a differential role for wine was based on in vitro data. While approximately 90% of the alcohol component is readily absorbed across the small intestine into the blood stream, it has only been relatively recently established from in vivo data that the wine-derived phenolic compounds are absorbed into the blood stream in sufficient quantity to act as effective antioxidants (Maxwell et al. 1994, Whitehead et al. 1995, Fuhrman et al. 1995, Nigdikar et al. 1998, Abu-Amsha Caccetta et al., 1999, Leighton et al. 1999, Abu-Amsha Caccetta et al., in press).

In vitro antioxidant activity of wine-derived phenolic compounds

In vitro studies have demonstrated that the wine-derived phenolic compounds may prevent and even reverse the oxidation of LDL, and hence prevent and reduce the accumulation of oxidised LDL in arteries (Witzum and Steinberg 1991, Halliwell and Chirco 1993, Whitehead et al. 1995, Abbey and Kerry 1996). In vitro studies have also demonstrated that under certain conditions, the wine-derived phenolic compounds increase the antioxidant capacity of blood plasma and serum (Kondo et al. 1994, Maxwell et al. 1994, Struck et al. 1994, Fuhrman et al. 1995, Simonetti et al. 1995, Whitehead et al. 1995, Abu-Amsha et al. 1996, Kerry and Abbey 1997, Carbonneau et al. 1997, Miyagi et al. 1997, Soleas et al. 1997a) and are, collectively and individually, 10—20 fold more antioxidative than a-tocopherol or vitamin E, which is an endogenous antioxidant (Frankel et al. 1993, Kanner et al. 1994, Rice-Evans et al. 1995, 1996). These studies also demonstrated that wine, specifically, does confer protection against the oxidation of LDL by free radicals in blood plasma (Witzum et al. 1991, Abu-Amsha et al. 1996, Miyagi et al. 1997), in particular when the plasma concentration of vitamin E was being depleted. The protection is dose-dependent where red wine is 10—20-fold more protective than is white wine (Frankel et al. 1995, Croft et al. 1996, Miyagi et al. 1997).

A question of considerable concern has been whether these in vitro or test tube data reflect accurately what is happening in the human body. In vivo or human clinical studies are required to demonstrate what is accurately happening in the human body.

In vivo antioxidant activity of wine-derived phenolic compoundsOnly eight in vivo studies have been undertaken to date and the results of these data are less clear cut than that of the in vitro studies. Six of the eight studies conducted have demonstrated that the wine-derived phenolic compounds are active antioxidants in vivo (Maxwell et al. 1994, Sharpe et al. 1995, Whitehead et al. 1995, Fuhrman et al. 1995, de Rijke et al. 1996, Nigdikar et al. 1998, Leighton et al. 1999, Abu-Amsha Caccetta et al. in press). Any inconsistencies in the results may reflect differences in study design and duration as well as in the analyses used to assess antioxidant activity. Indeed, significant antioxidant activity may only be observed following the medium- to long-term consumption of wine, although the phenolic compounds are absorbed in significant amount after the acute or short-term consumption of wine (Abu-Amsha Caccetta et al. in press). Reversal of endothelial dysfunction by wine-derived phenolic compounds

There may be another cardio-protective mechanism exerted by the wine-derived phenolic compounds. This mechanism, which is related to the initiation and development of atherosclerosis, is the restoring of blood vessel wall function or tone (Celemajer et al. 1994, Leighton et al. 1999, Stein et al. 1999, Cuevas et al. 2000). Blood vessel wall or endothelial dysfunction is where the endothelium is unable to relax and is constantly contracted or constricted and hence narrowed. This may be due to a decreased production of endothelial nitric oxide or an inactivation of nitric oxide by oxidative free radicals (Vogel et al. 1998), and is allied to another risk factor for cardiovascular disease, such as high blood pressure. It is often observed in cigarette smokers, and patients with diabetes and/or with an unbalanced lipid (HDL:LDL) concentration ratio who have significantly increased free radical or oxidative damage and stress (Morrow et al. 1995, Reilly et al. 1996). Furthermore, endothelial dysfunction is often observed before any anatomical vascular signs of atherosclerosis appear, such as the build up of oxidised-LDL on the endothelium (Celemajer et al. 1994).

Antioxidants, such as plant-derived phenolic compounds, have been observed to modify or reverse endothelial dysfunction (Andriambeloson et al. 1998, Aminbakhsh and Mancini 1999). For example, the wine-derived phenolic antioxidants have been observed in animal and in vitro studies (Fitzpatrick et al. 1993, Cishek et al. 1997, Andriambeloson et al. 1997, Fiesch et al. 1998, Andriambeloson et al. 1998) and in vivo studies to directly restore or increase their production of nitric oxide. This, in turn, restores the ability of the endothelium to relax with concomitant dilation of the blood vessels (Leighton et al. 1999, Cuevas et al. 2000, Stoclet et al. 2000). As anticipated, this vaso-relaxation also has a beneficial effect on blood pressure, but occurs only after medium to long-term moderate wine consumption (Djousse et al. 1999).

Interestingly, in an in vivo study that assessed the impact of a high-fat ‘western’ diet with and without the consumption of wine, the diet induced endothelial dysfunction in the subjects, but the concomitant consumption of red wine prevented it (Cuevas et al. 2000).Antithrombotic activity of wine-derived phenolic compounds

A second role for the wine-derived phenolic compounds, complementary to that of the ethanol component of wine, is in reducing platelet aggregation or blood clotting activity, that is, thrombosis. It was previously considered that the ethanol component of wine was solely responsible for the reduced risk of thrombosis observed following the consumption of wine and other alcoholic beverages.

Both ethanol and the wine-derived phenolic compounds suppress platelet aggregatability, which is the accumulation and clumping together of blood cells (Davis et al. 1970, Renaud et al. 1979 and 1981, Rand et al. 1988, Hendriks et al. 1994, Ridker et al. 1994). The data also suggests that red wine suppresses platelet aggregatability at a significantly lower blood alcohol concentration than does ethanol alone (Maalej et al. 1997). Specifically, wine-derived phenolic compounds have been observed to down-regulate cellular adhesion processes, which are responsible for the recruitment and activation of red blood cells and their subsequent clotting together at the site of vascular damage (Rotondo et al. 2000).

Other benefits of wine consumption

Risk factors for cardiovascular disease include: a high body mass index (height to weight ratio); a diet high in fats and low in fruits, grains and vegetables; a lack of exercise; cigarette smoking; an unbalanced plasma cholesterol concentration (ratio of HDL to LDL); and a high blood pressure pressure (Hunter et al. 1995, Norrish et al. 1995, Wieslisbach et al. 1997). Interestingly, consumers of wine generally are observed to have a healthier diet, exercise more, smoke less and have a lower level of other risk factors for cardiovascular disease (Klastsky et al. 1990, Klatsky and Armstrong 1993), while consumers preferring beer usually consumed more alcohol, smoked more, exercised less, and consumed more fatty foods and less fish, fruit and vegetables than did abstainers or consumers of wine (Beilin et al. 1996). Consumers of spirits may have the least favourable patterns and practices (Klatsky and Armstrong 1993).

The consumption of different alcoholic beverages has also been associated with different patterns of consumption and with different dietary and nutritional practices, such that, wine is also associated with a different pattern of consumption to that of spirits and beer. For example, only wine is generally consumed as an integral component of a meal (Klatsky et al. 1990). This pattern of wine consumption attenuates the blood alcohol concentration achieved, prolongs any short-term plasma anti-oxidative and anti-thrombotic effects, promotes any long-term effects, and prevents any rebound effects of the ethanol and phenolic components of the beverage. Populations that regularly consume a moderate amount of alcohol with a meal, such as those of the Mediterranean countries, and of central and southern France, have a significantly lower risk of cardiovascular disease (St Leger et al. 1979, Renaud and de Lorgeril 1992, Renaud 1996).Conclusion

Thus, while the moderate consumption of all alcoholic beverages has the ability to prolong life, it appears that wine consumption may confer additional health benefits. These additional benefits are related to protecting the cardiovascular system from the early and generally undetectable effects of atherosclerosis, and to overall healthier lifestyle practices. However, the magnitude and significance of these additional benefits has yet to be determined.

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This article was published in the The Australian & NewZealand Grapegrower & Winemaker, issue 446.

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