Critique 232: Does moderate drinking of alcohol in later life reduce the risk of mortality? 3 September 2019

Keyes KM, Calvo E, Ornstein KA. Rutherford C. Fox MP, Staudinger UM, Fried LP.  Alcohol Consumption in Later Life and Mortality in the United States: Results from 9 Waves of the Health and Retirement Study.  Alcoholism: Clin Exper Res 2019;43:1734-1746.

Authors’ Abstract

Background: Alcohol consumption in later life has increased in the past decade, and the relationship between alcohol consumption and mortality is controversial. Recent studies suggest little, if any, health benefit to alcohol. Yet most rely on single–time point consumption assessments and minimal confounder adjustments.

Methods: We report on 16 years of follow-up from the Health and Retirement Study (HRS) cohorts born 1931 to 1941 (N = 7,904, baseline mean age = 61, SD = 3.18). Respondents were queried about drinking frequency/quantity. Mortality was established via exit interviews and confirmed with the national death index. Time-varying confounders included but were not limited to household assets, smoking, body mass index, health/functioning, depression, chronic disease; time-invariant confounders included baseline age, education, sex, and race.

Results:  After adjustment, current abstainers had the highest risk of subsequent mortality, consistent with sick quitters, and moderate (men: HR = 0.74, 95% CI: 0.60 to 0.91; women: HR = 0.82, 95% CI: 0.63 to 1.07) drinking was associated with a lower mortality rate compared with occasional drinking, though smokers and men evidenced less of an inverse association. Quantitative bias analyses indicated that omitted confounders would need to be associated with ~4-fold increases in mortality rates for men and ~9-fold increases for women to change the results.

Conclusions: There are consistent associations between moderate/occasional drinking and lower mortality, though residual confounding remains a threat to validity. Continued efforts to conduct large-scale observational studies of alcohol consumption and mortality are needed to characterize the changing patterns of consumption in older age.

Forum Comments

A majority of meta-analyses (Di Castelnuovo et al; Ronksley et al) and long-term follow up analyses from prospective cohort studies (Fuchs et al, van Dam et al, Rimm et al, Pai et al, Baer et al; Gaziano et al) have shown that light-to-moderate consumers of alcohol have a lower risk of mortality than do lifetime abstainers and ex-drinkers; the latter include studies adjusting for competing causes of death (Baer et al).  However, a number of recent studies have raised concerns that such protection may be due to selection bias or residual confounding (Kerr et al, Keyes and Miech, Greenfield and Kerr).  Further, there are few studies that focus on consumption among older subjects.

The present study may be important as it describes the risk of mortality among a large group of subjects in a nationally representative cohort of men and women in the USA, the Health and Retirement Study.  It focuses on cohorts that were born in 1931 – 1941, with mortality over a follow-up period of about 16 years related to alcohol intake after 56 years of age.  A strength of this paper is that the authors had repeated assessments of alcohol intake (data on frequency and quantity, and whether there was binge drinking) and other time-variable factors, so changes in consumption could be evaluated.

Subjects were classified as current drinkers, lifetime abstainers, current abstainers (but presumably former drinkers), and occasional (less than 1 drink/week) drinkers.  Men were classified as heavy drinkers if they reported averaging more than 3 drinks/day or binge drinking (greater than 5 drinks/day), while women were classified as heavy drinkers if they averaged more than 2 drinks/day or binge drinking (greater than 4 drinks/day); moderate drinkers were men reporting 1-3 drinks/day without binge drinking and women reporting 1-2 drinks/day without binge drinking.

The authors conclude that, in comparison with subjects reporting never consuming alcohol, those reporting occasional drinking and those reporting moderate drinking after age 56 were found to have a lower risk of total mortality.  The authors also carried out quantitative bias analysis studies to estimate the effects of residual confounding on their results; these analyses indicate that it is very unlikely that residual confounding by unrecorded variables would be the cause of the reduction in mortality associated with moderate drinking.

Comments by individual Forum members:  Forum member Parente noted: “Notwithstanding the restraint of its conclusion and abstract, this study has many strengths (large population study of nearly 8,000; follow up of 16 years; stratification of drinkers/nondrinkers; numerous confounders assessed over time; consumption assessments at more than one point in time), including its statement that the quantitative bias analyses showed that ‘omitted confounders would need to be associated with ~4-fold increases in mortality rates for men and ~9-fold increases for women to change the results.’ Impressive.”

Reviewer Parente continued: “Survival analyses supported notably decreased mortality for moderate drinkers and, perhaps unsurprisingly, less robust results for male smokers. The usual argument that light or moderate drinkers tend to have less severe or fewer common diseases and to enjoy better health and socioeconomic status is addressed in this study, which accounted for time-varying confounders that included ‘household assets, smoking, body mass index, health/functioning, depression, chronic disease; [while] time-invariant confounders included baseline age, education, sex, and race.’  The findings of this study echo the report of Xi et al who followed > 333,000 participants over a median of 8.2 years and that similarly stratified alcohol consumption patterns into six groups of subjects and reported reduced mortality risk for all causes among light or moderate alcohol consumers.  Those authors reported a hazard ratio for light drinkers of 0.79 and for moderate drinkers of 0.78, in comparison with lifetime abstainers.”

Reviewer Skovenborg provided an overview of the underlying cohort, the authors, and the results:  “The study cohort, The Health and Retirement Study (HRS), is a nationally representative longitudinal survey of more than 37,000 individuals over age 50 in 23,000 households in the USA.  The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels.  Notably, it has previously reported that moderate alcohol use confers reduced frailty risk for both older men and women (Shah et al); that moderate alcohol use predicts fewer depressive symptoms among older adults (Paulson et al); and that social interaction is essential to the seemingly beneficial effect of moderate alcohol use on depressive symptomatology and functional ability (Scott et al).  While the authors are highly qualified epidemiologists engaged in the study of healthy aging versus frailty, their previous publications suggest prejudice against alcohol and a skeptical attitude regarding potential health benefits of alcohol consumption.”

Skovenborg continued: “The study design enumerates the well-known problems with observational studies of alcohol and health, but what makes this study so fascinating is that the study design addresses most of these epidemiological problems and still reaches the following conclusion: ‘In summary, the associations indicating potential health benefits of moderate drinking are increasingly viewed with skepticism . . . Nevertheless, the HRS is among the largest and most well-designed cohorts of older adults anywhere in the world, and within these data, we do find substantial associations between occasional and moderate drinking and lower mortality rates, compared to lifetime abstainers.’  As noted above by Parente, regarding residual confounding, these authors state that omitted confounders would need to be associated with very large increases in mortality rates to change the results.”

Forum member McEvoy stated: “I agree that this paper makes an important contribution to the literature on alcohol use and mortality. The ability to treat alcohol as a time-varying exposure is a major strength, and the results on the current abstainers are quite intriguing. I also appreciated that analyses were stratified by sex. The study was able to control for many potential confounders, and the quantitative bias analysis suggests that results are unlikely to be due to unmeasured confounders. The moderate drinking group contains quite a range of drinking (eg, it ranges from 1 drink/week up to average of 21 drinks/week for men) and it would have been informative to break this down more. Altogether, I think this is a well done analysis using a valuable data resource that provides firm support of a protective association of alcohol with reduced risk of mortality in both men and women.”

Reviewer Pajak agreed with these critiques: “There are clear strengths of the paper including multiple assessments of alcohol intake, addressing known problems of confounding and reversed causality to the extent not achievable for the vast majority of studies to date, and interesting simulation analysis to estimate the effects of a number of potential confounders. The results are striking!”

Reluctance of some scientists to admit to any beneficial effects on health of moderate drinking:  Forum member Ellison commented: “Despite decades of many observational studies, animal experiments, and limited clinical trials that show moderate alcohol intake to have favorable effects on a number of diseases and on mortality, it is noted that some researchers appear to be loath to admit such positive health effects.  We all appreciate the serious adverse effects of heavy or inappropriate drinking and of alcohol use disorders on the health of persons and on the community.  However, even in well-done analyses with clear results, it is disturbing that some scientists continue to question any beneficial results and insist on focusing only on the dangers of abuse.”

Reviewer Finkel had some cogent comments on this paper: “There have been a lot of unfounded assumptions expounded about the generic fragility of older individuals vis-à-vis alcohol since before I was old enough to drink, and that’s a long time.  They are generally without supportive clinical or experimental evidence.  Older folk are heir to the same benefits associated with moderate drinking as younger people, maybe more of them, and are not generally dramatically brought to grief by a dram.  I have read and written about many studies demonstrating this.

“The present paper adds more such evidence, but also provides the usual confusion and reluctance to accept the drinking benefits.  Witness the first words many will read, the beginning of the abstract indicating that the relationship is controversial and that ‘Recent studies suggest little, if any, benefit to alcohol’; then a waffling conclusion.  And the summarizing paragraph at the end accentuates the negative; and so it is all through wherever the authors can squeeze in an editorializing word.  Such statements detract from an otherwise clear report, making this part research results, part polemic.”

References from Forum critique:

Baer HJ, Glynn RJ, Hu FB, Hankinson SE, Willett WC, Colditz GA. Stampfer M, Rosner B.  Risk Factors for Mortality in the Nurses’ Health Study: A Competing Risks Analysis.  Am J Epidemiol 2011;173:319–329.  doi: 10.1093/aje/kwq368.

Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, De Gaetano G.  Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med 2006;166:2437–2445.

Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med 1995;332:1245–1250.

Gaziano JM, Gaziano TA, Glynn RJ, et al.  Light-to-moderate alcohol consumption and mortality in the physicians’ health study enrollment cohort.  J Amer Coll Cardiol 2000;35:96-105.  DOI: 10.1016/S0735-1097(99)00531-8.

Greenfield TK, Kerr WC.  Physicians’ prescription for lifetime abstainers aged 40 to 50 to take a drink a day is not yet justified. Alcohol Clin Exp Res 2014;38:2893–2895.

Kerr WC, Greenfield TK, Bond J, Ye Y, Rehm J.  Racial and ethnic differences in all-cause mortality risk according to alcohol consumption patterns in the national alcohol surveys. Am J Epidemiol 2011;174:769–778

Keyes KM, Miech R.  Commentary on Dawson et al: drink to your health?  Maybe not. Addiction 2013;108:723–724.

Pai JK, Mukamal KJ, Rimm EB.  Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study.  Eur Heart J 2012;33:1598–1605.  doi: 10.1093/eurheartj/ehs047

Paulson D, Shah M, Herring D, et al. The relationship between moderate alcohol consumption, depressive symptomatology, and C-reactive protein: the Health and Retirement Study. Int J Geriatr Psychiatry 2018;33:316-324.

Rimm EB, Giovannucci EL, Willett WC, et al.  Prospective study of alcohol consumption and risk of coronary disease in men.  Lancet 1991;338:464-468.

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.d67.

Scott RG, Wiener CH, Paulson D.  The Benefit of Moderate Alcohol Use on Mood and Functional Ability in Later Life: Due to Beers or Frequent Cheers?  Gerontologist 2018; doi: 10.1093/geront/gny129.

Shah M, Paulson D, Nguyen V. Alcohol Use and Frailty Risk among Older Adults over 12 Years: The Health and Retirement Study. Clin Gerontol 2018;41:315-325.

van Dam RM, Li T, Spiegelman D, Franco OH, Hu FB.  Combined impact of lifestyle factors on mortality: prospective cohort study in US women.  BMJ 2008;337:a1440. doi: 10.1136/bmj.a1440.

Xi B, Veeranki SP, Zhao M, Ma C, Yan Y,  Mi J, et al.  Relationship of Alcohol Consumption to All-Cause, Cardiovascular, and Cancer-Related Mortality in U.S. Adults.  J Am Coll Cardiol. 2017;70:913-922.

Forum Summary

There are well-known problems inherent in most observational studies of alcohol and health.  In addition to having to rely on self-report of intake, these include single-time point consumption assessments, inadequate confounder adjustments, accounting for reverse causation, selection bias, short follow up, residual confounding, and lacking information on chronic health conditions that may mediate the association between alcohol consumption and mortality.  Further, there have been a lot of assumptions expounded about the generic fragility of older individuals in terms of alcohol consumption; they are generally without supportive clinical or experimental evidence.  For light to moderate intake, the elderly tend to have similar benefits associated with alcohol as younger people, and they are at an age when the risk of mortality is at its peak.

The present study was able to adjust for many of these factors: it describes the risk of total mortality among a large group of older subjects, who were ≥ 56 years of age at the start of a 16 year follow up.  They were participants in a nationally representative cohort of men and women in the USA, the Health and Retirement Study.  Its strengths, in addition to its large size, is the fact that there were repeated assessments of alcohol so that changes of intake could be evaluated, and the authors were able to judge the potential importance of residual confounding.

The authors conclude that occasional drinking and moderate drinking among older subjects are associated with a lower risk of total mortality.  The usual argument that light or moderate drinkers tend to have less severe or fewer common diseases and to enjoy better health and socioeconomic status is addressed in this study, which accounted for time-varying confounders that included smoking, body mass index, income, health/functioning, depression, and chronic diseases.  From quantitative bias analysis studies they were able to estimate the effects of residual confounding on their results; the authors conclude that it is very unlikely that residual confounding by unrecorded variables would be the cause of the reduction in mortality associated with moderate drinking.  Survival analyses supported notably decreased mortality for moderate drinkers.  Forum members considered that this study adds important information about the effects on mortality of moderate drinking in the elderly.

Despite many decades of observational data, animal experiments, and limited clinical trials showing beneficial effects on many diseases and mortality from moderate drinking, it is noted that some researchers appear to be loath to admit to any positive health effects of alcohol.  We all appreciate the serious adverse effects of heavy drinking and alcohol use disorders, both on the health of persons and on the community.  However, when well-done analyses provide reliable data for light-to-moderate drinkers who do not binge drink, it is disturbing that, even then, some scientists question the observed beneficial results and appear to focus only on warnings about abuse.

There is evidence of a disinclination to admit to any beneficial effects of alcohol in many papers, including this one, which throughout the text seems to accentuate the negative aspects of alcohol.  Such statements detract from an otherwise clear report suggesting, as one reviewer stated, that this paper is part research results, part polemic.  In the opinion of the Forum, this paper provides strong evidence indicating that elderly people who are light-to-moderate drinkers tend to have a lower risk of mortality.

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

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

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

Ramon Estruch, MD, PhD, Hospital Clinic, IDIBAPS, Associate Professor of Medicine, University of Barcelona, Spain

Harvey Finkel, MD, Hematology/Oncology, Retired (Formerly, Clinical Professor of Medicine, Boston University Medical Center, Boston, MA, USA)

Fulvio Mattivi, MSc, CAFE – Center Agriculture Food Environment, University of Trento, via E. Mach 1,  San Michele all’Adige, Italy

Linda McEvoy, PhD, Department of Radiology, University of California at San Diego (UCSD), La Jolla, CA, USA

Professor Andrzej Pająk, Epidemiology and Population Studies, Jagiellonian University Medical College, Kraków, Poland

Matilda Parente, MD, consultant in molecular pathology/genetics and emerging technologies, San Diego, CA, USA.

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

Creina Stockley, PhD, MSc Clinical Pharmacology, MBA; Adjunct Senior Lecturer at the University of Adelaide, Australia

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

Andrew L. Waterhouse, PhD, Department of Viticulture and Enology, University of California, Davis, USA