Latest scientific news 23 July 2015

Twin studies help clarify causality regarding benefits of moderate alcohol consumption

The results of a twin study showed an inverse association between usual consumption of alcoholic beverages and long-term coronary artery disease (CAD) mortality risk that was independent of traditional risk factors, genetic and common environmental factors shared by twins. It strongly supports a causal association between the CAD risk and a moderate consumption of alcoholic beverages.

Countless epidemiological studies examined the association between alcohol use and cardiovascular disease. In the case of coronary artery disease (CAD), most studies observed the lowest disease risk among light to moderate drinkers, whereas abstainers and heavy drinkers had highest rates of CAD (1).

This J- or U-shaped association did not change when adjusting for potential confounders. However, associations from such cohort studies do not prove causality. Since it is logistically and ethically impossible to conduct a randomized clinical trial with alcoholic beverages as intervention, other study designs are needed to test the causal nature of this relationship.

One of these designs is to use twin and longitudinal family-based cohort studies. Twins are a valuable source for observation because they allow studying varying family environments (across pairs) and widely differing genetic makeup. Monozygotic (MZ) or „identical” twins share nearly 100% of their genes, which means that differences in disease outcomes between the twins must be due environmental or lifestyle differences. “Fraternal” or dizygotic (DZ) twins share only about 50% of their genes. Because twin brothers are matched on age, sex, family background, and partially (for dizygotic twins) or fully (for monozygotic twins) for genetic background, this design adjusts for many known and unknown factors affecting risk. The classical twin design compares the similarity of monozygotic (identical) and dizygotic (fraternal) twins. If identical twins are considerably more similar than fraternal twins (which is found for most traits), this implicates that genes play an important role in these traits. By comparing many hundreds of twin families, the roles of genetic effects and shared environment can be better understood. In the case of alcoholic beverages, these studies compare sets of siblings who differed in their alcohol consumption as adults (1).

Recently, a group of American epidemiologists analysed 41-year follow-up data from 843 male twins (396 pairs and 51 unpaired twins), aged 42-55 y at baseline (1969-1973), in the prospective National Heart, Lung, and Blood Institute Twin Study (2). It focused on the influence of alcohol consumption on coronary artery disease (CAD). The overall mortality risk from all causes as well as from CAD and cardiovascular were examined.

The analyses of all the participants showed that per 10 g alcohol intake per day at baseline, the CAD risk was reduced significantly by 6%. For cardiovascular disease, the risk was lowered by 3 % which was only marginally significant. Total mortality risk was not affected. Similar results were seen for the analyses within the twin pairs where the twin brother difference in alcohol consumption was examined to find out whether the higher consuming brother had a lower risk of CAD than the brother who drank less. The results did not change when adjusting for known CAD risk factors.

The participants of the study were moderate drinkers with an average of 8.6 g/d at baseline and 90% of participants drinking < 30.9 g/d. Since only 19 CAD deaths occurred among the heavy drinkers (in the 5th highest level of alcohol consumption), the study was not powerful enough to detect a J- or U-shaped association and is only informative about the association from 0 to 33 g alcohol per day. However, this study demonstrated an inverse association between the consumption of alcoholic beverages and the mortality risk from CAD. With the twin males as participants, in addition to the known risk factors, it provided new evidence on the relationship, accounting for numerous unknown factors shared between twins. It included familial factors such as behavior, parental demographic and socio-economic status shared among family members and common environmental factors from outside the family such as cultural norms towards drinking of alcoholic beverages. The authors conclude that this twin analysis is strongly supportive of a causal association between moderate alcohol consumption and a lowered CAD mortality risk. (2)

1. Kaprio J. Is the association between alcohol use and coronary artery disease causal? Evidence from a long-term twin study. Am J Clin Nutr 2015;102(1):1-2.

For more information about this article, read the scientific abstract here.

2. Dai J, Mukamal KJ, Krasnow RE, et al. Higher usual alcohol consumption was associated with a lower 41-y mortality risk from coronary artery disease in men independent of genetic and common environmental factors: the prospective NHLBI Twin Study. Am J Clin Nutr 2015;102(1):31-9.

For more information about this article, read the scientific abstract here.