ABSTRACT. Objective: Previous meta-analyses of cohort studies indicate a J-shaped relationship between alcohol consumption and allcause mortality, with reduced risk for low-volume drinkers. However, low-volume drinkers may appear healthy only because the "abstainers" with whom they are compared are biased toward ill health. The purpose of this study was to determine whether misclassifying former and occasional drinkers as abstainers and other potentially confounding study characteristics underlie observed positive health outcomes for lowvolume drinkers in prospective studies of all-cause mortality. Method: A systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. Results: Without adjustment, meta-analysis of all 87 included studies replicated the classic J-shaped curve, with low-volume drinkers (1.3-24.9 g ethanol per day) having reduced mortality risk (RR = 0.86, 95% CI [0.83, 0.90]).Occasional drinkers (<1.3 g per day) had similar mortality risk (RR = 0.84, 95% CI [0.79, 0.89]), and former drinkers had elevated risk (RR = 1.22, 95% CI [1.14, 1.31]). After adjustment for abstainer biases and quality-related study characteristics, no significant reduction in mortality risk was observed for low-volume drinkers (RR = 0.97, 95% CI [0.88, 1.07]). Analyses of higher-quality bias-free studies also failed to find reduced mortality risk for low-volume alcohol drinkers. Risk estimates for occasional drinkers were similar to those for low-and medium-volume drinkers. Conclusions: Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health. (J. Stud. Alcohol Drugs, 77, 185-198, 2016)

Questions about typical quantities of alcohol consumed can lead to underestimates, as do questions about drinking 'standard drinks' of alcohol. Recent recall methods encourage fuller reporting of volumes plus more accurate estimates of unrecorded consumption and the proportion of total alcohol consumption that places drinkers at risk of harm. However, they do not capture longer-term drinking patterns. It is recommended that both recent recall and measures of longer-term drinking patterns are included in national surveys.

The majority of prospective studies on alcohol use and mortality risk indicates that abstainers are at increased risk of mortality from both all causes and coronary heart disease (CHD). This meta-analysis of 54 published studies tested the extent to which a systematic misclassification error was committed by including as 'abstainers' many people who had reduced or stopped drinking, a phenomenon associated with ageing and ill health. The studies judged to be error free found no significant all-cause or cardiac protection, suggesting that the cardiac protection afforded by alcohol may have been over-estimated. Estimates of mortality from heavier drinking may also be higher than previously estimated.

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