Are there non-linear relationships between alcohol consumption and long-term health?: a systematic review of observational studies employing approaches to improve causal inference

Background: Research has long found ‘J-shaped’ relationships between alcohol consumption and certain health outcomes, indicating a protective effect of moderate consumption. However, methodological limitations in most studies hinder causal inference. This review aimed to identify all observational studies employing improved approaches to mitigate confounding in characterizing alcohol–long-term health relationships, and to qualitatively synthesize their findings. Methods: Eligible studies met the above description, were longitudinal (with pre-defined exceptions), discretized alcohol consumption, and were conducted with human populations. MEDLINE, PsycINFO, Embase and SCOPUS were searched in May 2020, yielding 16 published manuscripts reporting on cancer, diabetes, dementia, mental health, cardiovascular health, mortality, HIV seroconversion, and musculoskeletal health. Risk of bias of cohort studies was evaluated using the Newcastle-Ottawa Scale, and a recently developed tool was used for Mendelian Randomization studies. Results: A variety of functional forms were found, including reverse J/J-shaped relationships for prostate cancer and related mortality, dementia risk, mental health, and certain lipids. However, most outcomes were only evaluated by a single study, and few studies provided information on the role of alcohol consumption pattern. Conclusions: More research employing enhanced causal inference methods is urgently required to accurately characterize alcohol–long-term health relationships. Those studies that have been conducted find a variety of linear and non-linear functional forms, with results tending to be discrepant even within specific health outcomes. Trial registration: PROSPERO registration number CRD42020185861.