Purported Protective Effects of Alcohol Largely Non-causal

Based on decades of studies that have found associations between self-reported alcohol use at a point in time and disease in follow-up many years later, it has almost become dogma that consuming low amounts of alcohol is protective against cardiovascular disease. But higher-quality studies suggest that these effects are attributable to study methodology, not alcohol. Another large study (n=512,715 Chinese adults, 10 years of follow-up) confirms this conclusion. Some 160,000 participants were genotyped for variants involved in alcohol metabolism and participated in a Mendelian randomization study.

• Conventional epidemiological analyses adjusted for demographics and smoking found “U-shaped” curves for stroke and coronary heart disease, with nadirs for people who reported drinking occasionally and those drinking 100 g ethanol in a week on average (about 7 US standard drinks).
• In the genotypic analyses, there was a linear association between genotype-predicted mean alcohol consumption and stroke risk (with alcohol accounting for 8% of all ischemic strokes and 16% of all intracerebral hemorrhages in men), and no association (protective or harmful) with coronary heart disease.
• Of note, both self-reported alcohol and genotype-predicted means were associated linearly with known alcohol effects (systolic blood pressure, HDL cholesterol, and gamma-glutamyl transferase).

Comments: No study is perfect, nor can a single study answer a question definitively. But we now have several Mendelian randomization studies and several high-quality meta-analyses that have minimized confounding and biases and suggest that the previously observed associations between consumption of low amounts of alcohol and cardiovascular outcomes are not cause and effect.

Richard Saitz, MD, MPH

Reference: Millwood IY, Walters RG, Mei XW, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. Lancet. 2019;393(10183):1831–1842.