An inverse association between low to moderate alcohol intake and cardiovascular disease (CVD) has been demonstrated in many studies, but whether or not males and females differ in their response to alcohol is not known. This study tested whether alcohol effects differ by sex. The investigators performed a new meta-analysis of studies reporting dose-response effect of alcohol intake on vascular risk, separately for males and females. The study included altogether 184,791 persons across 12 studies. Dose-response curves (relative risks at different amounts of alcohol intake) for each study were used to construct an average “trend” curve for both men and women. The best fitting models include a negative linear term and a positive quadratic term, resulting in a “J-shaped curve,” similar to that previously reported for studies on general populations.
The authors report that the predicted dose-response models were very similar for both sexes, but the estimates of effect were slightly greater for women. At 12 g of ethanol per day the relative risk was 0.83 in males and 0.72 in females. A maximum reduction of 0.80 in males and 0.66 in females was predicted in both groups at 18-24 g of ethanol per day, but statistical significance was only reached up to the amount of 12 g of ethanol per day.
The graph above from the paper shows the predicted relative risks for vascular disease for different categories of alcohol consumption, separately for females (white bars) and males (black bars). The reference was the category of no consumption.
The figure shows that the protection against vascular disease is greater for women at lower levels of alcohol intake, whereas at the upper levels, adverse effects was higher for women than for men.
The authors state that a better effect of alcohol in women might be explained by several factors, such as increased high density lipoprotein cholesterol levels, better endothelial protective effects, or decreased insulin resistance; or because equivalent alcohol doses result in higher blood levels of alcohol in women due to women’s smaller size, larger body fat proportion, and reduced gastric metabolism of ethanol. The latter interpretation seems to be consistent with the data presented, that the small (though non-significant) advantage of women over men observed at the lowest amounts of alcohol was lost and even reversed at the highest doses.
The authors point out that one should also consider that men binge-drink more frequently than women. As a different sex-related protective role of alcohol was mainly observed for wine consumption in a meta-analysis by the authors, and in the study of Klatsky et al (in which women were more likely to drink wine), the authors cannot exclude that sex-related differences might be related not only to alcohol itself, but also to additional properties of wine. They were unable, however, to retrieve studies evaluating wine effects in comparable groups of male and female subjects.
Finally, the protective effect of moderate alcohol consumption has also been related to the regions where studies were conducted; e.g., in the Mediterranean area, the effect of alcohol appears to be stronger than in other areas, and this can be partially explained by the different pattern of consumption (generally, the regular consumption of wine with meals). However, the authors could not collect enough information on sex-related effect of alcohol in different regions, because 11 out of 12 studies included in their meta-analysis were conducted in non-Mediterranean areas. Thus, a sex-related difference of alcohol or wine might be confined to Mediterranean populations.
The authors conclude that large studies are needed to test either whether women are more susceptible to the benefit of wine (or alcohol) or whether they are more likely to drink lower amounts, thus taking its maximal advantage. In relation to the reported association between even moderate alcohol consumption and increased risk of female breast cancer, the overall effect of moderate wine intake may actually be favorable in postmenopausal women, in whom the protective effect on cardiovascular events might overcome the risk of breast cancer, but further epidemiological evidence is needed to definitely assess this important issue.
Source: Di Castelnuovo A, Iacoviello L, Furman K, Donati MB, de Gaetano G. Wine, alcohol and cardiovascular risk: open issue. Is wine or alcohol more beneficial in women? J Thromb Haemost 2004;2:20422044.