Critique 046: All-cause mortality rates are lower among moderate drinkers than among abstainers. – 4 July 2011

Fuller TD.  Moderate alcohol consumption and the risk of mortality.  Demography 2011.  DOI 10.1007/s13524-011-0035-2

Author’s Abstract

There has been a growing consensus that moderate consumption of alcohol is associated with a lower risk of mortality and that this association is probably causal.  However, a recent review article has raised a serious challenge to this consensus.  In short, it determined that most prior research in this area committed serious misclassification errors; furthermore, among those studies that were free of these misclassification errors, no support for a protective role of alcohol consumption was found.  

This article reexamines the issue using prospective data for more than 124,000 persons interviewed in the U.S. National Health Interview Surveys of 1997 through 2000 with mortality follow-up through 2002 using the Linked Mortality File.  The study involves about 488,000 person-years.  Controlling for a variety of covariates, this study finds that compared with nondrinkers, those who consume a moderate amount of alcohol have lower all-cause and CHD mortality.  The fact that the current study has taken care to avoid the pitfalls of some earlier studies and still finds that those who consume a moderate amount of alcohol have lower all-cause mortality and CHD mortality lends credence to the argument that the relationship is causal.

Forum Comments

Background and overview:  These analyses support the majority of population-based prospective studies that have shown that moderate drinkers are at lower risk of death from coronary heart disease (CHD) as well as the risk of all-cause mortality.  A poorly done paper in 20061 raised questions about potential “errors” in the vast majority of  epidemiologic studies, stating that they did not account for sick quitters or occasional drinkers in their analyses.  In 2007, the proceedings were published from a conference of scientific experts in the field (including the first author of the earlier paper1) that focused considerable discussion on this topic.  The consensus was that the earlier paper presented a biased view on the topic, and misrepresented the overall scientific findings.2,3  Further, almost all recent studies have shown that these concerns were not well-founded, as when studies avoid the potential “errors” they still found the same results: lower CHD risk for moderate drinkers. 

Two recent articles in the BMJ4,5 have provided excellent summaries of current scientific data on this topic.  Indeed, one Forum reviewer thought that the present paper was “superfluous,” as this topic has been adequately dealt with in many previous publications.  He added: “Skeptical people who cannot be convinced by the two articles in the BMJ may be ideologists who are unable or unwilling to accept scientific arguments.”  Nevertheless, even recently a number of groups and policy makers6,7 seem to have ignored most recent research and continue to use these same arguments to deny most of the beneficial health effects of moderate drinking.  In contrast, other policy makers (e.g., the scientists who recently released the 2010 Dietary Guidelines for the USA8) have apparently based their guidelines on what Forum members consider to be more up-to-date, accurate, and balanced data.

Specific Comments on paper:  The author of the present study has carried out extensive analyses on a very large number of subjects.  He claims that his study refutes arguments that “errors” in many previous studies negate their results, and he concludes that this study lends credence to the argument that the relationship between moderate alcohol intake and lower mortality is causal, and not due to associated health behaviors of moderate drinkers.

In the present study, the author adjusted for a very large number of potential confounders, many of which had not been considered in previous studies.   In addition to age, sex, and race/ethnicity, the author adjusted for education, marital status, work status, smoking status, and income.  Further, he adjusted for self-reported health, previous health conditions, and binge drinking. With all of these adjustments, the hazard ratios for mortality were considerably greater for abstainers, and for some heavy drinkers, than they were for essentially all categories of subjects reporting alcohol consumption. 

Forum reviewers recognized some limitations in the present study: numbers in each category of alcohol use are not given, and unadjusted results are not presented (making it impossible to evaluate the effects of specific confounding variables).  Further, while the classification of “moderate drinking” includes both amount and frequency of consumption to some degree, it is difficult to tease apart the two components.  Also, the results related to total mortality are probably more reliable than those related to CHD, as the latter is often misdiagnosed on death certificates.  Overall, Forum members agreed that the author did a good job and there were no problems in terms of how the effect estimates were obtained, even with multiple factors and interaction terms in the model. 

Determining causation in epidemiologic studies:  Some Forum members emphasized the known difficulties in judging causation of the beneficial effects of alcohol on health outcomes sorely from observational studies, even prospective ones; there is always the possibility of residual confounding.   Obviously, in epidemiologic studies, the amounts of alcohol and foods consumed, and descriptions of all other factors, are only an approximation, and do not have the accuracy seen in animal experiments or in human clinical trials.  And most studies have not included data on genetic factors that may modify the exposure to alcohol. 

Still, the consistency of observational data among a wide variety of populations; the strong support from animal experiments showing biological effects of both alcohol and polyphenols; and the results from an increasing number of human clinical trials of the effects of alcohol/polyphenols on many mechanisms of cardiovascular disease support a causative effect of moderate drinking on CHD and on other diseases of ageing.  Further, a number of studies have reached the conclusion that no set of potential confounders thus far recognized could explain the lower risk of heart disease among drinkers that has been demonstrated in most studies. 

References from Forum  Review

1.  Fillmore KM, Kerr WC, Stockwell T, Chikritzhs T, Bostrom A.  Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies.  Addiction Research and Theory 2006;14:101–132.

2.  Rimm EB, Moats C.  Alcohol and coronary heart disease: Drinking patterns and mediators of effect.  Ann Epidemiol 2007;17:S3–S7.

3.  Panel Discussion I:  Does alcohol consumption prevent cardiovascular disease?  Ann Epidemiol 2007;17:S37–S39

4.  Brien SE, Ronksley PE,Turner BJ, Mukamal KJ, Ghali WA.  Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies.  BMJ 2011;342:d636; doi:10.1136/bmj.d636.

5.  Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA.  Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis.  BMJ 2011;342:d671; doi:10.1136/bmj.d671

6.  Summary of evidence.  Antioxidants in food, drinks and supplements for cardiovascular health.  2010.  National Heart Foundation of Australia. ABN 98 008 419 761.  ISBN: 978-1-921226-91-5.

7.  Global status report on alcohol and health.  World Health Organization 2011.  ISBN 978 92 4 156415 1 (NLM classification: WM 274)

8.  2010 Dietary Guidelines for Americans, US Departments of Agriculture and Health & Human Services, 2011.

Forum Summary

The author set out to determine the extent to which potential “errors” in many early epidemiologic studies led to erroneous conclusions about an inverse association between moderate drinking and coronary heart disease.  His analysis is based on prospective data for more than 124,000 persons interviewed in the U.S. National Health Interview Surveys of 1997 through 2000 and avoids the pitfalls of some earlier studies. 

The results of this analysis support the vast majority of well-done prospective studies and indicate that moderate consumers of alcoholic beverages have lower all-cause mortality and CHD mortality.  In this paper, non-drinkers had much higher risk of death than did almost all categories of subjects consuming alcohol.  The author contends that these results lend credence to the argument that the relationship between alcohol and mortality is causal.

While some Forum reviewers felt that this analysis only replicates what has been shown in many other papers, it appears that erroneous information continues to be used by some policy groups.  Thus, most reviewers believe that this new analysis provides important information on potential health effects of moderate drinking. 

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Comments by the International Scientific Forum on Alcohol Research on this paper have been provided by the following members:

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.

Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.

Maritha J. Kotze, PhD, Human Genetics, Dept of Pathology, University of Stellenbosch, Tygerberg, South Africa.

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway.

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.

Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia.

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa.

Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis.

Yuqing Zhang, MD, DSc, Epidemiology, Boston University School of Medicine, Boston, MA, USA.