Article Text

Are there non-linear relationships between alcohol consumption and long-term health? Protocol for a systematic review of observational studies employing approaches to improve causal inference
  1. Rachel Visontay1,
  2. Matthew Sunderland1,
  3. Tim Slade1,
  4. Jack Wilson1,
  5. Louise Mewton1,2
  1. 1The Matilda Centre for Research in Mental Health and Substance Use, The University of Sydney, Sydney, New South Wales, Australia
  2. 2Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia
  1. Correspondence to Dr Louise Mewton; louisem{at}


Introduction There is a substantial literature finding that moderate alcohol consumption is protective against certain health conditions. However, more recent research has highlighted the possibility that these findings are methodological artefacts, caused by confounding and other biases. While modern analytical and study design approaches can mitigate confounding and thus enhance causal inference in observational studies, they are not routinely applied in research assessing the relationship between alcohol use and long-term health outcomes. The purpose of this systematic review is to identify observational studies that employ these analytical/design-based approaches in assessing whether relationships between alcohol consumption and health outcomes are non-linear. This review seeks to evaluate, on a per-outcome basis, what these studies find the strength and form of the relationship between alcohol consumption and health to be.

Methods and analysis Electronic databases (MEDLINE, PsycINFO, Embase and SCOPUS) were searched in May 2020. Study selection will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles will be screened against eligibility criteria intended to capture studies using observational data to assess the relationship between varying levels of alcohol exposure and any long-term health outcome (actual or surrogate), and that have employed at least one of the prespecified approaches to enhancing causal inference. Risk of bias of included articles will be assessed using study design-specific tools. A narrative synthesis of the results is planned.

Ethics and dissemination Formal ethics approval is not required given there will be no primary data collection. The results of the study will be disseminated through published manuscripts, conferences and seminar presentations.

PROSPERO registration number CRD42020185861.

  • epidemiology
  • public health
  • statistics & research methods
  • substance misuse

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Supplementary materials


  • Contributors RV is the guarantor of the review. RV, MS, TS and LM conceptualised the study and developed the study design and protocol. RV wrote the first draft of the manuscript. RV, MS, TS, JW and LM contributed to, read, revised and approved the final manuscript.

  • Funding RV is funded by the National Health and Medical Research Council (GNT1190255) and the University of Sydney.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.