BACKGROUND AND AIMS: Evidence on the causal impact and corresponding risk relationships between dimensions of alcohol consumption and health outcomes continues to evolve, with some contradictory findings across study designs. This review aimed to update current knowledge on causality and risk relationships to inform global and national comparative risk assessments for alcohol. METHODS: Fully alcohol-attributable conditions were identified using International Classification of Diseases (ICD) 10th and 11th revision codes. We conducted a scoping review of meta-analyses of cohort studies on average consumption and health outcomes (56 reviews), a systematic review of Mendelian randomisation (MR) studies on alcohol and ischaemic heart disease (IHD; 20 studies), and narrative syntheses on injuries, biological pathways, and reversibility of effects. RESULTS: ICD-11 provides more detailed categories, defining 62 fully alcohol-attributable conditions compared with 48 in ICD-10. Meta-analyses support monotonic increasing dose-response relationships between average consumption and most attributable health outcomes within infectious diseases, cardiovascular diseases, cancers, and digestive diseases. Relationships are J-shaped for IHD, ischaemic stroke, and type 2 diabetes, with lower risk at low-to-moderate consumption (generally only without heavy episodic drinking). For dementia, heavy drinking is harmful and, among non-heavy drinkers, relationships are age-specific. MR evidence for IHD largely suggested null or harmful relationships, but only three studies tested non-linear effects. In our view, the overall synthesis indicates that current MR evidence is insufficient to refute a J-shaped relationship for IHD. Injury risk is driven primarily by acute intoxication and includes substantial harm to others. Acute risks are reversible with reductions in drinking or abstention, whereas many chronic disease processes are only partly reversible. CONCLUSIONS: Epidemiological evidence to inform comparative risk assessments for alcohol is comprehensive, but prone to major limitations. Triangulation, alongside biological plausibility, can strengthen synthesis across cohort and Mendelian randomisation studies, and the target trial framework can help future studies avoid design-induced biases. Comparative risk assessments with ischaemic heart disease should, at this point, prioritise evidence from cohort studies.
Carr et al. (Wed,) studied this question.