OBJECTIVE: Assumptions about alcohol's health benefits profoundly influence global disease burden estimates and drinking guidelines. Using theory and evidence, we identify and test study characteristics that may bias estimates of all-cause mortality risk associated with low-volume drinking.

METHOD: We identified 107 longitudinal studies by systematic review with 724 estimates of the association between alcohol consumption and all-cause mortality for 4,838,825 participants with 425,564 recorded deaths. "Higher-quality" studies had a mean cohort age of 55 years or younger, followed up beyond 55 years, and excluded former and occasional drinkers from abstainer reference groups. "Low-volume" alcohol use was defined as between one drink per week (>1.30 g ethanol/day) and two drinks per day (<25 g ethanol/ day). Mixed linear regression was used to model relative risks (RRs) of mortality for subgroups of higher- versus lower-quality studies.

RESULTS: As predicted, studies with younger cohorts and separating former and occasional drinkers from abstainers estimated similar mortality risk for low-volume drinkers (RR = 0.98, 95% CI [0.87, 1.11]) as abstainers. Studies not meeting these quality criteria estimated significantly lower risk for low-volume drinkers (RR = 0.84, [0.79, 0.89]). In exploratory analyses, studies controlling for smoking and/or socioeconomic status had significantly reduced mortality risks for low-volume drinkers. However, mean RR estimates for low-volume drinkers in nonsmoking cohorts were above 1.0 (RR = 1.16, [0.91, 1.41]).

CONCLUSIONS: Studies with lifetime selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks. Future research should investigate whether smoking status mediates, moderates, or confounds alcohol-mortality risk relationships.