The association between alcohol consumption and all-cause mortality: An umbrella review of systematic reviews using lifetime abstainers or low-volume drinkers as a reference group.

BACKGROUND AND AIMS: Systematic reviews of the relationship between alcohol consumption and all-cause mortality have reported different relative risk (RR) curves, possibly due to the choice of reference group. Results have varied from 'J-shaped' curves, where low-volume consumption is associated with reduced risk, to monotonically increased risk with increasing consumption. We summarised the evidence on alcohol consumption and all-cause mortality exclusively from systematic reviews using lifetime abstainers or low-volume/occasional drinkers as the reference group.

METHODS: We conducted a systematic umbrella review of systematic reviews of the relationship between alcohol consumption and all-cause mortality in prospective cohort studies using a reference group of lifetime abstainers or low-volume/occasional drinkers. Several databases (PubMed/Medline/Embase/PsycINFO/Cochrane Library) were searched to March 2022. Reviews were assessed for risk of bias, and those with reference groups containing former drinkers were excluded.

RESULTS: From 2149 articles retrieved, 25 systematic reviews were identified, and five did not include former drinkers in the reference group. Four of the five included reviews had high risk of bias. Three reviews reported a J-shaped relationship between alcohol consumption and all-cause mortality with significant decreased risk for low-volume drinking (RR range 0.84 to 0.95), while two reviews did not. The one review at low risk of bias reported monotonically increased risk with greater consumption (RRs = 1.02, 1.13, 1.33 and 1.52 for low-, medium-, high- and higher-volume drinking, respectively, compared with occasional drinking). All five reviews reported significantly increased risk with higher levels of alcohol consumption (RR range 1.28 to 3.70). Sub-group analyses were reported by sex and age; however, there were evidence gaps for many important factors. Conversely, 17 of 20 excluded systematic reviews reported decreased mortality risk for low-volume drinking.

CONCLUSIONS: Over 70% of systematic reviews and meta-analyses published to March 2022 of all-cause mortality risk associated with alcohol consumption did not exclude former drinkers from the reference group and may therefore be biased by the 'sick-quitter effect'.