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Alcohol Consumption And The Long-Term Risk Of Mortality

Alcohol Consumption And The Long-Term Risk Of Mortality


This study aims to update a previous systematic review by conducting a comprehensive analysis of meta-analyses published from January 1, 2017, to March 8, 2021, to quantify sex-specific dose–response risk relationships between chronic alcohol consumption and disease occurrence and mortality. The systematic search adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 5953 articles were identified, with 14 meeting the inclusion criteria for the narrative review.

The study focused on diseases and mortality associated with chronic alcohol consumption, comparing individuals who never consumed at least one standard drink of alcohol. Measurements included relative risks, odds ratios, and hazard ratios based on long-term alcohol intake measured in grams per day.

The findings indicate that all diseases examined demonstrated an increased risk of occurrence with higher levels of alcohol consumption. Specifically, chronic alcohol use was significantly linked to detrimental effects on tuberculosis, lower respiratory infections, oral cavity and pharyngeal cancers, esophageal cancer, colorectal cancer, liver cancer, laryngeal cancer, epilepsy, hypertension, liver cirrhosis, and pancreatitis among men. However, protective effects from low-dose chronic alcohol use were observed for ischemic heart disease, ischemic stroke, and intracerebral hemorrhage among both men and women. Low-dose alcohol consumption also exhibited protective effects for diabetes mellitus and pancreatitis among women, with protective thresholds identified at approximately 50 g/day and 30 g/day, respectively.

In summary, the study underscores that alcohol use has a dose–response relationship with various infectious and noncommunicable diseases. While higher levels of alcohol use are consistently associated with detrimental health impacts, lower levels exhibit both disease-specific protective and detrimental effects. The research emphasizes the nuanced relationship between alcohol consumption and health outcomes, acknowledging the complexity of these interactions.


The study underscores the causal association between alcohol consumption and the onset and mortality of various infectious and noncommunicable diseases, establishing it as a leading risk factor for global death and disability. Supported by reputable sources such as Griswold et al. (2018), IARC Working Group (2012), and the World Health Organization (2018), the research emphasizes the multifaceted nature of alcohol use, encompassing chronic volume, acute consumption, usage patterns, and contextual factors.

Chronic alcohol use significantly influences health and disease occurrence in proportion to the volume consumed. The impact is typically gauged through metrics such as relative risks (RRs), odds ratios (ORs), and hazards ratios (HRs), crucial for individuals and policymakers. At the population level, these metrics are instrumental in modeling hospitalizations, disease burden, and social costs attributable to alcohol use. They also aid in projecting potential changes if alcohol public health policies were altered. At the individual level, these metrics, when coupled with burden of disease statistics, estimate the health repercussions of alcohol consumption, facilitating the formulation of low-risk drinking guidelines and policy recommendations.

Despite numerous systematic reviews and meta-analyses quantifying alcohol-related RRs, ORs, and HRs, variations exist in terms of publication dates, inclusion/exclusion criteria, and methodological approaches. The study aims to address these disparities by systematically searching and reviewing meta-analyses reporting alcohol dose–response curves across different levels of average daily alcohol use and disease outcomes. An additional goal is to assess whether RRs, ORs, and HRs exhibit sex-based differences.

To achieve these objectives, the study adopts a meticulous approach, selecting systematic reviews and meta-analyses of the highest quality. Utilizing a standard set of quality criteria, the research ensures a robust evaluation of alcohol-related health impacts. This emphasis on methodological rigor is crucial in advancing our understanding of the nuanced relationship between alcohol consumption, disease outcomes, and potential variations based on sex.


The study serves as an update to the 2020 Australian Guidelines to Reduce Health Risks from Drinking Alcohol (2007–2020) by the National Health and Medical Research Council (NHMRC) and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It encompasses a systematic review of new literature, assessing the correlation between chronic alcohol use and disease risk from 2017 to 2022.

To conduct the review, a comprehensive search strategy was employed, utilizing databases such as PubMed, PsycNET, Embase, Cochrane Database of Systematic Reviews, among others. The search focused on articles published between January 1, 2017, and March 8, 2021, with additional inclusion of studies related to the formulation of Australian alcohol guidelines. An information specialist screened results, removing duplicates and irrelevant articles based on project scope. Two investigators independently evaluated articles for inclusion based on titles, abstracts, and full texts, resolving discrepancies through discussion.

Data extraction from relevant articles included authors’ names, publication dates, study designs, participant sex, number of studies, inclusion/exclusion criteria, alcohol consumption ascertainment, measures of association (RR, OR, and/or HR), reference groups for these measures, and 95% confidence intervals. Continuous RR functions were extracted when available, and if not, categorical RR estimates were utilized. For studies presenting risk functions graphically, authors were contacted for additional details.

Assessment of study eligibility followed the Population, Exposure, Comparator, and Outcomes (PECO) framework. Methodological quality evaluation employed A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and Risk of Bias in Systematic Reviews (ROBIS) tools. The quality of the 14 selected systematic reviews was further appraised using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system and AMSTAR 2 instrument. The selection prioritized the most recent systematic reviews addressing potential confounding factors, with a substantial number of cohort studies, particularly those with younger participants at baseline.

The study focused on extracting relative risk (RR) estimates from the chosen 14 meta-analyses, modeling them based on alcohol consumption categories or a continuous distribution. RRs based on a continuous distribution considered incremental alcohol consumption, often in increments like every 10g increase in daily consumption. The reference group for RRs was lifetime abstainers, a choice justified by the inclusion of former drinkers in the abstention group. Importantly, no transformations or imputations were applied to the extracted RRs, and all tables and figures were generated using the R statistical program.

Inclusion Criteria

Inclusion criteria for articles were established based on specific parameters: (a) qualification as a systematic review of epidemiological studies, (b) publication in either English or French, (c) primary focus on chronic alcohol use as the exposure of interest, (d) comparison with individuals who have never consumed a standard drink of alcohol (i.e., lifetime abstention), (e) primary outcome centered on disease occurrence and/or mortality, (f) disease causally linked to alcohol use according to criteria from IHME (Griswold et al., 2018), WHO (World Health Organization, 2018), or IARC (IARC Working Group, 2012), (g) adjustment for the confounding factor of age in the underlying risk estimates, and (h) execution of a dose–response or dose-stratified meta-analysis involving RRs, ORs, and/or HRs. These stringent criteria aimed to ensure the selection of high-quality systematic reviews with a specific focus on chronic alcohol use and its impact on disease occurrence and mortality, providing a robust foundation for the study’s objectives.


The study, building upon the 2020 Australian Guidelines to Reduce Health Risks from Drinking Alcohol, conducted a systematic review encompassing literature from 2017 to 2022. Out of 5953 references, 50 studies meeting strict eligibility criteria were selected, with 14 identified as high-quality systematic reviews. These reviews investigated chronic alcohol use’s impact on disease occurrence and mortality, spanning various categories such as infectious, noncommunicable, and neurological diseases. Among the findings, increased alcohol consumption exhibited a dose-dependent escalation in the risk of tuberculosis, lower respiratory infections, oropharyngeal, esophageal, larynx, colorectal, liver, and breast cancers, diabetes mellitus, epilepsy, cardiovascular diseases, and digestive diseases.

The meticulous selection process considered factors like study design, exposure definitions, outcome definitions, statistical analyses, and sex-specific analyses. Notably, sex-specific risk differentials were observed, revealing varying impacts on disease occurrence between men and women. For instance, higher relative risks were identified among men for colorectal cancer, diabetes mellitus, hypertension, and pancreatitis, while women faced an increased risk of breast cancer with elevated alcohol consumption. Protective effects were noted for diabetes mellitus in women, contrasting with the heightened risks of liver cirrhosis and pancreatitis.

Despite certain limitations in reporting and methodology across selected systematic reviews, the study rigorously assessed the available evidence, providing valuable insights into the nuanced relationship between chronic alcohol use and diverse health outcomes.


This comprehensive review underscores the dose-dependent association between alcohol consumption and increased risks of multiple diseases. The study emphasizes a clear adverse impact on health, particularly at higher levels of alcohol consumption. While acknowledging the heightened risk in men for developing colorectal cancer, diabetes mellitus, hypertension, and pancreatitis per gram of alcohol consumed compared to women, the precise reasons for these sex-based differences remain unclear, necessitating further investigation. Factors such as heavy episodic drinking tendencies and variations in alcohol metabolism might contribute to these observed distinctions.

The review focuses exclusively on diseases coded under the ICD-10 system, considering only those fatal or nonfatal conditions monitored by the WHO or IHME. It encompasses 18 diseases, establishing a quantifiable dose–response risk relationship with chronic alcohol consumption. Notably, certain disease categories, although potentially related to alcohol, were excluded due to the absence of established causal relationships or non-fatal outcomes. The study identifies research gaps, stressing the need for more recent and robust studies to enhance understanding.

Methodologically, the review opts for lifetime abstention as the reference group over total abstention, accounting for differing risk levels between lifetime abstainers and former drinkers. This distinction is crucial to avoid potential biases and curvilinear relationships in modeling lifetime alcohol-attributable risk curves. Acknowledging limitations such as biases in reported relative risks and potential regression dilution bias, the review calls attention to the complexity of measuring chronic alcohol use, incorporating cross-sectional self-reported data.

While recognizing the limitations inherent in the selection of only one review per outcome and the impact of review recency, the study strategically updates risk estimates for various diseases, providing valuable insights into the nuanced relationship between alcohol consumption and health outcomes. The findings bear significant clinical and public health implications, urging a clearer understanding of low-volume alcohol use’s actual health benefits and risks. The study calls for unambiguous public health messaging to address potential confusion arising from conflicting information on alcohol consumption and underscores the critical role of ongoing research in elucidating the multifaceted relationships between alcohol use, disease, and various modifiers.

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