Review: Moderate Drinking Doesn’t Lower Mortality

A new comprehensive meta-analysis failed to find any protective effect of moderate drinking on mortality risk [1].

Linear or U-shaped?

There is an ancient idea that while excessive drinking will kill you, moderate alcohol consumption is actually good for you, and until recently, it seemed to be supported by scientific evidence. Several populational studies have found a U-shaped relationship between drinking and health, with the smallest risk of mortality being associated with low, but not zero, levels of alcohol consumption [2].

However, many scientists have always suspected that those studies might be misleading and plagued with biases such as “reverse causality”. In this case, zero drinkers are actually former drinkers who quit after developing health problems. As a result, their poor health skews the picture for the whole category of teetotalers [3]. Another type of bias is the “occasional drinker bias”, in which people who drink only on rare occasions are bundled with moderate drinkers, possibly boosting the overall health of this group.

Recent high-quality studies, including Mendelian randomization studies in which scientists use genetic variants associated with the investigated factor, such as variants that affect alcohol metabolism, seem to question the “U-shape” assumption [4]. Unfortunately, interventional trials are scarce, albeit some older ones suggest that even moderate alcohol consumption elevates blood pressure [5]. To summarize, the debate is far from over.

A comprehensive review

This new large-scale review of existing literature updates previous research conducted by the same group. It adds a considerable number of studies that appeared in recent years. The review now encompasses more than 100 studies published between January 1980 and July 2021, and almost five million people, with some studies following the same cohorts for decades.

The researchers categorized and weighed the studies, giving more prominence to those of a better quality. They also reran the analysis using occasional drinkers (less than 1 drink per week) rather than never-drinkers as a reference group and stratified the overall population of the studies by mean age (less than 65 or more than 65) and sex.

No benefits to moderate consumption

The results largely confirmed the hypothesis that moderate drinking does not confer any health benefits. Before adjusting for confounding variables and biases, low-volume drinkers (1.3-24.0 g of ethanol per day) indeed showed the lowest mortality risk of all groups. However, the difference between them and abstainers became insignificant in the fully adjusted model.

Occasional drinkers (0 to 1.3 grams of ethanol per day) also did not fare significantly better than lifetime abstainers. Interestingly, although the risk for moderate drinkers (25 to 44 grams per day) was slightly elevated, this difference also did not reach statistical significance. The only two groups who fared significantly worse than lifetime abstainers were moderate to heavy drinkers (45 to 64 grams per day) and heavy drinkers (65+ grams per day). Their relative mortality risk compared to lifetime abstainers was elevated by 19% and 35%, respectively. Shifting the reference group from lifetime abstainers to occasional drinkers did not significantly change the picture.

Interestingly, former drinkers had 26% more risk of death than lifetime abstainers, suggesting that alcohol-related damage cannot be fully reversed by staying off the bottle. When stratified by age, the younger than 65 cohort showed an even higher risk of death for moderate to heavy and heavy drinkers compared to lifetime abstainers. This can be interpreted as an even clearer sign that alcohol is bad for health (young people are generally healthier, which makes alcohol-induced damage more visible).

The association between alcohol and mortality was more pronounced in women, as female moderate drinkers (25 to 45 grams a day) were also at a significantly greater risk of dying than lifetime abstainers. This might be explained by women’s lower average body mass.

Conclusion

According to this new study, moderate drinking does not confer significant benefits in terms of mortality risk. However, it also does not seem to hurt. While this meta-analysis is comprehensive and prioritizes high-quality research, it does not constitute definitive proof, and we are looking forward to new Mendelian randomization and interventional studies.

Literature

[1] Zhao, J., Stockwell, T., Naimi, T., Churchill, S., Clay, J., & Sherk, A. (2023). Association Between Daily Alcohol Intake and Risk of All-Cause Mortality: A Systematic Review and Meta-analyses. JAMA Network Open, 6(3), e236185-e236185.

[2] Fillmore, K. M., Kerr, W. C., Stockwell, T., Chikritzhs, T., & Bostrom, A. (2006). Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies. Addiction Research & Theory, 14(2), 101-132.

[3] Thelle, D. S. (2020). Alcohol and heart health: the need for a randomized controlled trial. European Journal of Preventive Cardiology, 27(18), 1964-1966.

[4] Biddinger, K. J., Emdin, C. A., Haas, M. E., Wang, M., Hindy, G., Ellinor, P. T., … & Aragam, K. G. (2022). Association of habitual alcohol intake with risk of cardiovascular disease. JAMA network open, 5(3), e223849-e223849.

[5] Puddey, I. B., Beilin, L. J., Vandongen, R., & Rouse, I. L. (1985). A randomized controlled trial of the effect of alcohol consumption on blood pressure. Clinical and Experimental Pharmacology & Physiology, 12(3), 257-261.