Daily Alcohol Intake Appears More Dangerous than Not, Even in Small Doses and Particularly for Women

Daily low or moderate alcohol consumption was not associated with significant reductions in all-cause mortality, according to findings of a new systematic review and meta-analysis that involved more than 4.8 million participants.

Specifically, review authors found no protective effect of alcohol for drinkers who consumed <25 g/day (US alcoholic drink equivalent, 14g) and report that risk of all-cause mortality was significantly increased among women at lower levels of daily intake (≥25 g/day) than for men (≥45 g/day).

“The proposition that low-dose alcohol use protects against all-cause mortality in general populations continues to be controversial,” wrote Jinhui Zhao, PhD, a scientist at the Canadian Institute for Substance Use Research at the University of Victoria, and colleagues in JAMA Network Open.

“Observational studies tend to show that people classified as ‘moderate drinkers’ have longer life expectancy and are less likely to die from heart disease than those classified as abstainers,” they continued. “Systematic reviews and meta-analyses of this literature confirm J-shaped risk curves (protective associations at low doses with increasing risk at higher doses).”

The authors counter that additional evidence now suggests that the observed associations could be a result of “systematic biases that affect many studies,” eg, use of health indicators not associated with alcohol consumption, including diet, hygiene, annual income, and others. Further, when cohort samples have been adjusted to be more representative, apparent protective associations are eliminated.

A careful new analysis

The current analysis, wrote Zhao et al updates data from a previous similar systematic review and meta-analyses by the same team, incorporating recent studies and assessing and controlling for various sources of potential bias (lifetime selection, ill health among abstainers) and of confounding, the most important being misclassification of former drinkers and/or current occasional drinkers as abstainers/never drinkers.

The analysis also evaluated the association between mortality risk and alcohol consumption by median age and sex distribution in the full cohort.

Yield from the investigators’ systematic review was 107 cohort studies published between January 1980 and July 2021 that met inclusion criteria. For the analysis, Zhao et al identified 724 risk estimates of all-cause mortality due to alcohol intake across the 107 studies (n=4 838 825 and 425 564 deaths available).

FINDINGS

In models that were adjusted for the potential confounding effects of sampling variation across studies, former drinker bias, and other prespecified quality criteria for individual studies, the research teams meta-analysis found that compared with lifetime nondrinkers, there was no significantly reduced risk of all-cause mortality among occasional drinkers (>0 to <1.3 g/day; relative risk [RR], 0.96; 95% CI, 0.86-1.06; P= .41) or low-volume drinkers (1.3-24.0 g/day; RR, 0.93; P= .07).

In the model fully adjusted for a wide range of covariates investigators found a nonsignificant increase in risk for all-cause mortality among participants who drank 25 to 44 g/day (RR, 1.05; P = .28). Risk significantly increased, however, at greater amounts consumed per day to 1.19 for drinkers who ingested 45 to 64 g/day and to 1.35 for those consuming ≥65 g/day (P<.001 for both).

Higher risk at lower consumtpion for women

Among women who consumed alcohol, mortality risks were significantly larger compared with women who were never drinkers (RR, 1.22; P = .03).

The investigators also found that women who drank had a higher RR of all-cause mortality vs men across all levels of alcohol consumption and that the dangers of excess consumption began at lower levels of daily consumption. They report also that mortality risks were significantly higher among women who drank compared with women who were lifetime nondrinkers (RR, 1.22; P = .03).

The investigators also found that women who drank had a higher RR of all-cause mortality vs men across all levels of alcohol consumption and that the dangers of excess consumption began at lower levels of daily consumption.

Of note, Zhao and colleagues found that errors of misclassification of once-drinkers or those who drink occasionally as lifetime abstainers affected 86 out of the 107 studies in the analysis.

The authors summarized the analysis: “Our meta-analysis of 107 studies found (1) no significant protective associations of occasional or low-volume (moderate) drinking with all-cause mortality; and (2) an increased risk of all-cause mortality for drinkers who drank 25 g or more and a significantly increased risk when drinking 45 g or more per day.”

Low intake risky for all

When consumption exceeded 25 g/day, risk of all-cause mortality was higher for women than for men, including a significant increase in risk for women at medium-level consumption not seen for men, they wrote. “However, mortality risks for mean consumption up to 25 g/day were very similar for both sexes.”

They add that “future longitudinal studies in this field should attempt to minimize lifetime selection biases by not including former and occasional drinkers in the reference group, and by using younger cohorts (ie, age distributions that are more representative of drinkers in the general population) at baseline.”

Reference: Zhao J, Stockwell T, Naimi T, et al. Association between daily alcohol intake and risk of all-cause mortality: a systematic review and meta-analysis. JAMA Netw Open. 2023;6:e236185. Published online March 31, 2023. doi:10.1001/jamanetworkopen.2023.6185