Alcohol Drinking and Mortality

Critique 245: Effects of different patterns of alcohol consumption on risk of mortality, major cardiovascular events, cirrhosis, and cancer — 25 January 2021

Reference: Jani BD, McQueenie R, Nicholl BI, Field R, Hanlon P, Gallacher KI, Mair FS, Lewsey J. Association between patterns of alcohol consumption (beverage type, frequency and consumption with food) and risk of adverse health outcomes: a prospective cohort study. BMC Medicine 2021;19:8. https://doi.org/10.1186/s12916-020-01878-2.

This study was designed to determine factors that affect the pattern of alcohol consumption (including the frequency of consumption, type of beverage, with or without food, etc.), rather than just the reported average amount of alcohol, related to all-cause mortality, major cardiovascular events-MACE (MI/stroke/cardiovascular death), accidents/injuries, liver cirrhosis, all-cause and alcohol-related cancer incidence. It was based on a large prospective cohort study of UK Biobank (UKB) participants and included more than 300,000 subjects; outcomes were ascertained over a 9-year median follow-up period. Non-drinkers and only occasional drinkers were excluded from the analyses, so this paper does not judge the effects of light or moderate drinking versus not drinking, but only the effects of the pattern of reported alcohol consumption among regular drinkers.

The study showed that in comparison with subjects who consumed red wine more than 50% of the time (the reference group) there were lower risks of many adverse outcomes than among consumers of more than 50% of the time of spirits; the latter had 25% greater risk of all-cause mortality, 31% greater risk of MACE, and 48% higher risk of liver cirrhosis after controlling for total weekly alcohol consumption and relevant confounders. In comparison with red-wine drinkers, consumers of beer/cider showed an 18% higher risk for all-cause mortality, 16% higher risk of MACE, and 36% higher risk of liver cirrhosis. There were no statistically significant differences in outcomes between white wine drinkers and red wine drinkers.

Consumption of alcohol with food, versus not with food, showed a 10% (CI 2%-17%) lower risk of all-cause mortality. While consumers reporting alcohol consumption 3-4 days/week had lower risk of some adverse outcomes than subjects reporting intake on only 1-2 days/week, for some reasons subjects reporting daily or near-daily intake had an increased risk of liver cirrhosis, probably related to under-reporting by some heavy drinkers.

Forum members agree with the conclusions of this study as reported in the Authors’ Abstract: “Red wine drinking, consumption with food and spreading alcohol intake over 3–4 days were associated with lower risk of mortality and vascular events among regular alcohol drinkers, after adjusting for the effects of average amount consumed.” The results of this well-done study emphasize how inappropriate it is to use just the total average alcohol intake when relating the consumption of alcoholic beverages to the risk of adverse health outcomes.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

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

Reference: 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.

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.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, please click here.

Critique 220: An unusual analysis relating alcohol intake to mortality – October 16, 2018

Reference: Hartz SM, Oehlert M, Horton AC, Grucza RA, Fisher SL, et al. Daily Drinking Is Associated with Increased Mortality. Alcoholism: Clin & Experimental Research 2018; pre-publication. DOI: 10.1111/acer.13886.

The authors of this treatise on alcohol consumption and mortality combined, for an unclear reason, results from two, very different studies: one from the Veterans’ Health Administration, based on outpatient clinical medical records, and the other from a national survey in the USA [The National Health Interview Survey (NHIS)]. Unfortunately, the VA data did not adjust for tobacco use or other important lifestyle habits, and are not useful in judging the effects of alcohol consumption on mortality.

While the NHIS survey included data on potential confounding, both it and the VA study based their analyses on a single estimate of alcohol consumption. The authors then created a variable that they stated was associated with the lowest risk of mortality and compared results from such alcohol intake with data from subjects reporting less or more alcohol. They combined data on all subjects reporting 1 to 2 drinks/week, so did not have the ability to provide a precise estimate of the association between low levels of intake and mortality risk. They did not comment on the effects that under-reporting of alcohol would have on their studies (and most investigators agree that the self-reported level of alcohol consumption is usually an under-estimate of actual consumption). Further, they did not point out the very much higher risk of mortality of non-drinkers, compared with moderate drinkers, demonstrated in their data.

To the extent that people accurately reported their past drinking status (never vs former), this study should put to rest concerns that protective associations of drinking versus non-drinking arise from inclusion of former drinkers into non-drinking groups. Never drinkers had higher risk of mortality than former drinkers in this study.

There are considerable data from many well-done cohort studies that have repeated assessments of alcohol intake over many decades and the subsequent risk of mortality. Such studies provide very clear and consistent results indicating a J-shaped curve: lower risk of mortality for light and moderate drinkers than for non-drinkers (even lifetime abstainers) and some increase in risk for heavy drinkers. These are the studies that can provide reliable information upon which drinking guidelines for different individuals and populations can be based.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 216: Strong effects of five lifestyle factors on risk of mortality and longevity of life – 31 May 2018

Reference: Li Y, Pan A, Wang DD, Liu X, Dhana K, Franco OH, Kaptoge S, Di Angelantonio E, Stampfer M, Willett WC. Hu FB. Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation 2018;137:00–00. (Pre-publication). DOI: 10.1161/CIRCULATIONAHA.117.032047.

It has long been known that a number of lifestyle factors – such as not smoking, being physically active, avoiding obesity – decrease the risk of many of the “diseases of ageing,” especially cardiovascular disease and cancer. The present paper from the Nurses’ Health Study and the Health Professionals Follow-up Study is especially important as it demonstrates the joint effects of five healthy factors on disease-specific and total mortality in very large cohorts of subjects. The “healthy lifestyle factors” evaluated were (1) never smoking, (2) body mass index of 18.5 to 24.9 kg/m2, (3) ≥30 min/d of moderate to vigorous physical activity, (4) moderate alcohol intake, and (5) a high diet quality score (upper 40%). The similarity in education and other socio-economic factors of the subjects in these studies tends to reduce potential confounding by such factors.

There were more than 42,000 deaths in their cohorts during follow-up periods extending up to 34 years. The effects of these factors on subsequent risk of mortality were striking: for subjects meeting criteria for all five factors versus none, there was an 84% reduction in all-cause mortality, 65% less cancer mortality, and 82% less cardiovascular disease mortality. The overall effect was associated with 12 to 14 additional years of life after age 50 for subjects meeting criteria for all five factors.

Forum members consider this to be an excellent study, as it was based on data from very large cohorts of well-monitored subjects over many decades, with essentially full ascertainment of mortality. This study strongly suggests that the leading causes of premature death throughout the developed world are, to a large extent, preventable.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 215: Long-term effects of smoking and moderate drinking on the quality and longevity of life of elderly women — 9 May 2018

Reference: Nelson HD, Lui L, Ensrud K, Cummings SR, Cauley JA, Hillier TA. Associations of Smoking, Moderate Alcohol Use, and Function: A 20-Year Cohort Study of Older Women. Gerontology & Geriatric Medicine 2018;4:1–9. Pre-publication.

While essentially all epidemiologic studies have shown adverse health effects of cigarette smoking and beneficial effects of moderate alcohol consumption, the present study is important as it follows a cohort of elderly women into very old age. It is a prospective cohort study of 9,704 women at least 65 years of age, who were living independently at baseline and were not heavy drinkers; they had a mean baseline age of 71.7 years (range 65-99) and underwent repeated assessments of lifestyle habits starting in 1986 to 1988. They were followed longitudinally until death, loss to follow-up, or to April, 2016. Outcomes included grip strength, walking speed, prevalence of threshold scores for self-reported health, difficulty with three or more instrumental activities of daily living (IADLs), depression, prevalence of falls, living in a nursing home, and death after 10- or 20-year follow up. The main comparisons evaluated in this study were between women who were smokers and those who consumed alcohol moderately, with each analysis adjusted for the other exposure.

Forum members considered this to be a well-done study that provides some important data relating effects of smoking and moderate drinking on function and mortality in very elderly subjects (an age group where data are lacking). There were criticisms that the study does not report the effects of moderate drinking among smokers; previous studies have shown that the adverse effect of smoking is modified by moderate alcohol intake. Further, given that the reasons why some women quit drinking during follow up are not known, the article does not contribute to clarification of the problem of reverse causation (e.g., healthier women may tend to continue drinking whereas sicker women stop alcohol consumption). Also, the authors did not adjust for some strong confounders, especially those related to socio-economic status (SES).

Nevertheless, the results of this study make a real contribution to our knowledge of the effects of drinking on both quality of life and mortality among women who are 65 years or older. The follow up of subjects continued for a least 20 years, by which time almost 70% of the women had died. Hence, the effects on mortality should be excellent estimates. As expected, women who were smokers had greater risk for almost all adverse outcomes, while drinkers who continued to consume moderate alcohol into old age had the most favorable outcomes. While the authors report that women who reported drinking at baseline but quit later on had mortality risks that were intermediate between non-drinkers and persistent drinkers, the reasons why some women quit drinking were not known. Hence, it is appreciated that continued drinking could be only a marker of better health, and not the cause.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 205: A very large population-based study of the association of alcohol consumption with total and disease-specific mortality – 4 September 2017

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

The usual finding in longitudinal cohort studies has been that light-to-moderate consumers of alcohol tend to be at lower risk for total mortality and show greater longevity of life, even when other lifestyle/demographic factors known to affect longevity are adjusted for in the analysis. The present analysis is important as it presents data on the relation of alcohol intake to total mortality as well as to specific mortality from cardiovascular disease (CVD) and cancer for a very large number of subjects in the USA. It is based on data from more than 300,000 subjects, of whom almost 25,000 died during a follow-up period averaging 8.2 years. There was a very large number of lifetime abstainers which could serve as an appropriate reference group for their analyses. Further, by adjusting for a number of chronic diseases, and carrying out sensitivity analyses with a 2-year lag period for mortality, the investigators improved their ability to avoid having their results affected by “sick quitters.”

The authors conclude that their analysis shows that light and moderate drinkers have a lower risk of total mortality, as well as mortality from CVD, heart disease, and cerebrovascular disease. The protective effects of alcohol for such cardiovascular outcomes were not present for subjects who reported binge drinking or for those reporting what was defined as “heavy” drinking (>7 drinks/week for women and older men, 14 drinks/week for younger men). Interestingly, the mortality risk for light and moderate drinking was also significantly reduced for deaths attributed to cancer; Forum members thought that this may have possibly resulted from subjects with cancer who actually died from CVD having their deaths attributed to cancer. Subjects reporting heavy drinking and those with binge drinking showed increased risk of all-cause and cancer mortality, with no significant effect on CVD outcomes. The key results of the study are that there is a very clear J-shaped curve for the relation of alcohol to mortality, with lower total, cardiovascular, and even cancer mortality rates for light and moderate drinkers who do not binge drink. There was increased total mortality and cancer mortality for those classified as “heavy” drinkers.

Forum Members thought it unfortunate that beverage-specific data were not presented (as in many studies wine, and sometimes beer, drinkers have better outcomes than consumers of spirits), that subjects of all ages (≥ 18 years of age) were included in a single analysis (rather than also presenting results specifically for older subjects, when the outcome events studied usually occur), and especially that women and older men who consumed > 7 drinks/week, and younger men consuming >14 drinks/week were all combined into a “heavy” drinking category. It would have been preferable that the investigators also had a category for those consuming only slightly more than the recommended levels, who may well have had different outcomes than heavier drinkers.

Overall, Forum members considered this to be a well-done study providing additional data supporting a J-shaped curve for the association of alcohol consumption with mortality. Thus, data continue to indicate that light-to-moderate intake of alcoholic beverages without binge drinking reduces total mortality as well as death from CVD or cancer. The cumulative scientific data on this topic are well described in the accompanying Editorial Comment by de Gaetano and Constanzo in the same issue of the journal.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 204: Moderate drinking improves the chances for healthy survival to age 85 – 21 August 2017

Reference: Richard EL, Kritz-Silverstein D, Laughlin GA, Fung TT, Barrett-Connor E, McEvoy LK. Alcohol Intake and Cognitively Healthy Longevity in Community-Dwelling Adults: The Rancho Bernardo Study. J Alzheimer’s Dis 2017;9:803–814. DOI 10.3233/JAD-161153

A number of studies have shown that the risk of cognitive impairment appears to be reduced among elderly subjects who consume moderate amounts of alcohol; most studies indicate that both light and moderate drinking are associated with a lower risk of dementia, but heavy drinking is often shown to be associated with higher cognitive risk for dementia and cognitive impairment. In some studies, a protective effect of light-to-moderate alcohol intake has been seen primarily among consumers of wine, or sometimes beer/wine. Further, almost all well-done cohort studies have shown that moderate drinkers tend to have longer lifespans.

The present study is based on a group of ageing subjects in California that had been observed closely for several decades; the average follow-up period for these particular analyses were about 14 years. Subjects in this cohort have had multiple assessments of cognitive ability and frailty. The authors conclude that their subjects who reported moderate alcohol consumption in the late 1980s were more likely than non-drinkers during follow up to survive to age 85 years of age, and also to be more likely to survive to age 85 cognitively intact (without evidence of dementia). Also, daily or near-daily drinkers had better health outcomes than those of non-drinkers or less-frequent drinkers.

The Forum considers this to be a well-done study; while it is not based on a large cohort, it provides new data by having extensive evaluation over time in a cohort of community-dwelling elderly subjects. The results support data from most other studies of survival and dementia among moderate drinkers, but adds specific information on survival to age 85 without cognitive impairment.

This study and the review of prior scientific data on this subject led Forum members to also raise a question about the typical guidelines for alcohol consumption for the elderly: generally less or no alcohol consumption is advised. Given that current scientific data show that the risks of the common disease outcomes of older subjects (e.g., coronary artery disease, ischemic stroke, osteoporosis, dementia, mortality) are lower among moderate drinkers than among non-drinkers, it may be time to reevaluate such restrictions that are based on age alone.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 201: The marked effect of lifestyle on mortality — 26 June 2017

Reference: Larsson SC, Kaluza J, Wolk A. Combined impact of healthy lifestyle factors on lifespan: two prospective cohorts. J Int Med 2017. Pre-publication. Doi: 10.1111.joim.12637.

The aim of the present study was to examine differences in the risk of mortality and in survival associated with a healthy lifestyle versus a less healthy lifestyle. The analyses were based on a total of more than 60,000 Swedish men and women who were followed in one of two studies; at baseline, the subjects were aged 45 to 83 years and were free of cancer and cardiovascular disease. The goal was to evaluate the effects of four “healthy” lifestyle factors: (1) nonsmoking; (2) physical activity at least 150 min/week; (3) alcohol consumption of 0–14 drinks/week; and (4) a healthy diet, with the latter defined as a modified Dietary Approaches to Stop Hypertension (DASH) Diet score above the median. Cox proportional hazards regression models and Laplace regression were used to estimate respectively hazard ratios of all-cause mortality and differences in survival time.

The authors report: “Compared with individuals with no or one healthy lifestyle factor, the multivariable hazard ratios of all-cause mortality for individuals with all four health behaviors were 0.47 (95% confidence interval [CI] 0.44-0.51) in men and 0.39 (95% CI 0.35-0.44) in women. This corresponded to a difference in survival time of 4.1 (95% CI 3.6-4.6) years in men and 4.9 (95% CI 4.3-5.6) years in women.”

Forum members considered this to be a well-done study on a large cohort with complete follow-up data on mortality. Notable weaknesses included the fact that never drinkers and consumers of 0 to 14 drinks/week were considered in one group (thus, including lifetime abstainers, ex-drinkers, and current moderate drinkers); these subjects were compared with consumers of >14 drinks/week. Thus potential differences between abstinence versus light/moderate consumption could not be determined. Further, there were incomplete data on the pattern of drinking, and no data on the type of beverage consumed were reported. Nevertheless, the reduction in mortality for subjects following a healthy lifestyle was impressive: a reduction by half, or more, in the risk of mortality and a 4- to 5-year longer lifespan.

Based on a number of previous studies that evaluated similar lifestyle factors and mortality, the results of this study were not unexpected. Still, they strongly support the remarkable effects on mortality and survival of these lifestyle factors. While not smoking was clearly the factor with the strongest effect on reducing mortality, having a healthy diet, exercising, and consuming light to moderate amounts of alcohol all make additional contributions. This is an important message in that even individuals who may be challenged by genetic or socioeconomic predispositions to earlier demise, adopting certain lifestyle habits can help them reach their greatest potential for a longer and healthier lifespan.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 194: Long-term alcohol use and mortality among Swedish women – 22 November 2016

Reference: Licaj I, Sandin S, Skeie G, Adami H-O, Roswall N, Weiderpass E. Alcohol consumption over time and mortality in the Swedish Women’s Lifestyle and Health cohort. BMJ Open 2016;6:e012862. doi:10.1136/ bmjopen-2016-012862

In a follow-up analysis of almost 50,000 young women, aged 30-49 at baseline, in the Swedish Women’s Lifestyle and Health cohort, the authors used self-reported information on alcohol consumption on two occasions, 12 years apart, to estimate the effects of alcohol on overall and cause-specific mortality. There were 2,100 deaths during follow up. Effects of alcohol on the two occasions, and changes between the two assessments among 33,000 women with available data, were related to mortality, as assessed from virtually complete national records.

Using “light” drinkers (0.1 – 1.49 grams of alcohol/day) as the referent group, the authors report an inverse association between greater amounts of alcohol consumption and mortality from cardiovascular disease. They report increased risk of cardiovascular and total mortality for abstainers. Despite the large number of total subjects, the authors report results separately for relatively narrow ranges of alcohol intake (none, 0.1-1.49, 1.5-4.9, 5-9.9, 10-14.9, 15+ g/day), which makes the numbers of subjects in many groups quite small. Given that the total mortality risks for most groups of drinkers were similar, it would have been interesting to see the effects of alcohol consumption (versus no consumption) using a broader definition of “moderate” drinking.

Forum members in general thought that this was a well-done study, using an excellent source of national records available in Sweden for determining mortality. They had concerns that the under-reporting of alcohol intake was not addressed; there is a high probability that some of the supposedly “light” drinkers may have actually consumed more alcohol, which would tend to decrease any differences between the referent group and the next groups of drinkers. This could help explain why, despite the strikingly lower risk ratios for cardiovascular disease for all drinkers when compared with the referent group, the inverse relation of alcohol was not statistically significant for any single group considered alone.

The Forum was also concerned that while the investigators had data on binge drinking and whether or not alcohol was usually consumed with meals, they chose not to include these data in their analyses. Given that drinking pattern plays a large role in determining favorable or unfavorable health effects of alcohol, the inclusion of such information may have better delineated the true effects of alcohol. Also, the authors “chose not to separately study the effects of different alcohol beverages;” reporting effects separately for beer, wine, and spirits could have provided key data on the effects of alcohol consumption.

The attempt of the authors to judge the effects of changes in alcohol intake during the study is laudable. Importantly, data on the reason that a woman may decide to increase or decrease her intake is not known; if due to the development of a serious disease, it may be the disease and not the change in alcohol intake that relates to subsequent mortality. However, given the inherent problems in assessing change, the results of this study are consistent with other studies that have suggested an increase in mortality risk for moderate drinkers who stop their alcohol consumption.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 183: An unusual analysis of the association of alcohol consumption with mortality — 24 March 2016

Reference: Stockwell T, Zhao J, Panwar S, Roemer A, Naimi T, Chikritzhs T. Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. J Stud Alcohol Drugs 2016;77:185–198.

The stated purpose of this new analysis was to determine whether misclassifying former and occasional drinkers as abstainers and other potentially confounding study characteristics underlie observed positive health outcomes for low volume drinkers in prospective studies of mortality. Unfortunately, the authors include in their analyses a number of old epidemiologic studies and do not acknowledge that when the “errors” that they have commented on in the past (such as including heavy ex-drinkers in the no-alcohol referent group) have been dealt with in the majority of studies over the past decade. The authors still exclude the vast majority of these well-done studies in their new meta-analysis. Results of essentially all studies that adjust for their concerns continue to show a significant and meaningful reduction in the risk of cardiovascular disease (CVD) and total mortality from the moderate intake of wine and alcohol.

Forum members note how very selective the authors are in choosing which papers to include in their new analyses: they identified 2,575 studies on the subject, analyzed 87, but then they found some reason to exclude almost all of these studies to reach a conclusion that “ . . . there was no significant protection for low-volume drinkers (RR = 1.04, 95% CI [0.95, 1.15])” based on what is apparently only 6 remaining studies! The paper ignores the comments by two other scientists (Roerecke & Rehm) who, like these authors, have in the past been very concerned that confounding and errors weaken the purported relation between alcohol and a lower risk of cardiovascular disease, but have more recently concluded: “For drinkers having one to two drinks per drinking day without episodic heavy drinking, there is substantial and consistent evidence from epidemiological and short-term experimental studies for a beneficial association with IHD risk when compared to lifetime abstainers. The alcohol-IHD relationship fulfills all criteria for a causal association proposed by Hill.”

The authors of the present paper also ignore the immense amount of experimental data, not only animal experiments but trials in humans, that have described the mechanisms by which moderate alcohol and wine intake have been shown to decrease essentially all of the risk factors for CVD, including low HDL-cholesterol, elevated LDL-cholesterol, endothelial dysfunction, coagulopathies, inflammation, abnormal glucose metabolism, and many others. The consistent finding of lower CVD risk among moderate drinkers in all well-done cohort studies is strongly supported by experimental evidence of the mechanisms.

In the opinion of Forum members, the present paper markedly distorts the accumulated scientific evidence on alcohol and CVD. As stated by one Forum member, “The biased selection of studies that are included undermines the value of the paper, but more importantly promulgates misinformation in the name of appropriate scientific method. Failure to acknowledge the robust body of knowledge that supports the opposite conclusion, and disqualification of extensive animal and cell culture studies that offer plausible biologic explanation of observed benefits, is unconscionable.”

The Forum concludes that the overwhelming body of observational scientific data, as well as an immense number of experimental studies, support the contention that, for most middle-aged and older men and women who choose to do so, the regular consumption of small amounts of an alcoholic beverage can be considered as one component of a “healthy lifestyle.” Such a habit has been shown to be associated with a lower risk of cardiovascular disease and of total mortality.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 180: The association of alcohol intake with total mortality risk among women — 9 February 2016

Reference: Midlöv P, Calling S, Memon AA, Sundquist J, Sundquist K, Johansson S-E. Women’s health in the Lund area (WHILA) – Alcohol consumption and all-cause mortality among women – a 17 year follow-up study. Pre-publication: BMC Public Health 2016;16:22. DOI 10.1186/s12889-016-2700-2.

The follow up of more than 6,000 women in a population-based cohort in an area of southern Sweden was used to estimate how baseline levels of alcohol consumption, at age 50-59 years, related to total mortality risk over the subsequent 17 years. At baseline, 26% of women reported no alcohol consumption while 13% reported an average of 12 or more grams of alcohol per day. Thus, the large majority (61%) were light drinkers, reporting the equivalent of no more than one drink per day. The authors report that, even when adjusting for education, marital status, smoking, BMI, physical fitness, diabetes and ischemic heart disease before screening, mortality risk during follow up was significantly higher among non-drinkers and heavier drinkers than among women reporting the equivalent no more than one typical drink per day. They state that their analyses thus support a “J-shaped” association between alcohol and total mortality risk, and that “The observed protective effect of light drinking (1–12 grams/day) could thus not be attributed to any of these known confounders.”

Forum members agreed this was a well-done study, but noted that the authors were unable to adjust for the pattern of drinking (regular versus binge), previous drinking among abstainers, or potential changes in drinking during follow up. Also, beverage-specific results are not presented. Further, the data presented in this study are not adequate to judge the specific level of alcohol consumption at which total mortality risk for drinkers reaches or exceeds the risk for non-drinkers; in other words, the “threshold” for adverse effects of alcohol on mortality cannot be determined very well. Nevertheless, the results of these analyses are very consistent with most long-term follow-up studies and support a “J-shaped” association between alcohol and the risk of total mortality.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 176: A New Report on Alcohol Consumption and Total Mortality Risk — 14 December 2015

Reference: Goulden R. Moderate Alcohol Consumption Is Not Associated with Reduced All-cause Mortality. Am J Med 2015; pre-publication. http://dx.doi.org/10.1016/j.amjmed.2015.10.013.

Most observational studies have found that moderate drinkers, in comparison with nondrinkers, tend to have lower risk of all-cause (total) mortality; this is probably related primarily to a reduction in the risk of cardiovascular disease, the leading cause of death among the elderly. This large study has conflicting findings, as the author claims that the present analyses do not demonstrate protection against mortality from light-to-moderate drinking. In this study, what were termed “occasional drinkers,” rather than nondrinkers, were used as the comparison group.

Forum members had two main concerns about this study that warrant an investigation of the author’s conclusions: there was no consideration of under-reporting of alcohol intake when declaring “occasional drinkers” as the referent group, and (2) the inclusion, and adjusting for as “confounders,” several factors that are actually mechanisms by which alcohol has been shown to reduce mortality.

The first concern could have led to many light drinkers being included in the referent group, and thus not evaluated for a potential protective effect of light drinking on mortality. In fact, presented only in the Appendix to the paper are data showing that when nondrinkers make up the referent group, consumers of 1-7 as well as 7-14 drinks per week show significant 20-30% reductions in the risk of mortality; these findings are very similar to those of most previous epidemiologic studies.

The second, and perhaps more important concern, is that some of the mechanisms by which moderate alcohol intake may lead to lower mortality, such as reducing the risk of diabetes and coronary heart disease, were “adjusted” for in the analyses. This would attenuate or even erase any true reduction in risk of mortality from moderate drinking.

Some Forum members also were concerned that some subjects were missing data on alcohol consumption but, rather than excluding them, an estimated value was imputed for them. Further, data on the pattern of drinking (regular moderate versus binge drinking) or on the type of beverage consumed were not included in the evaluation.

Forum members conclude that the results of this study will obviously be considered in conjunction with other scientific data when seeking to judge the relation of alcohol intake to mortality. However, concerns about the analysis raise questions about the conclusion of the author of no protective effect of alcohol on mortality, a finding that conflicts with the results of most previous studies.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 169: Effects of IQ on risk of morbidity and mortality related to alcohol consumption — 25 August 2015

Reference: Sjölund S, Hemmingsson T, Gustafsson JE, Allebeck P. IQ and alcohol-related morbidity and mortality among Swedish men and women: the importance of socioeconomic position. Journal of Epidemiology and Community Health 2015;69:858-864.

The present paper is based on a large cohort of subjects in Sweden who had IQ tests as children (when they were 13 years old) and were then followed for more than 30 years. The study reports an inverse association between childhood IQ and hospitalization for alcohol-related diseases or death. The association is strongly dose-dependent, with a marked increase in disease/mortality risk for each decrease in the childhood IQ score.

A key finding in this analysis is that the attained socio-economic status (SES) of the subjects at age 32 played a large role in explaining the association between IQ and alcohol-related disease and appeared to completely explain the association with death from alcohol-related causes. This suggests that much of the effect of IQ during childhood may be through its effect on later education, occupation, and income of the subjects, associations that have been noted in many previous epidemiologic studies to favor better health. It is reassuring that being born into a poor, uneducated family is not as important as a determinant of adverse effects of alcohol later in life as is the attained socio-economic status of the individual in young adulthood.

A possible explanation for the inverse relation of SES in young adulthood with adverse alcohol outcomes could relate to the type of beverage consumed, which was not evaluated in the present analysis. In a previous study from Denmark, it was shown that higher SES in young adults was associated with a strong preference for wine rather than for other types of alcoholic beverage. Wine consumption has been associated with better health in numerous studies, although it is unclear whether this is due primarily to the non-alcoholic constituents in wine or to confounding from associated lifestyle factors of wine drinkers.

Forum members agree with the authors that the underlying causes for an association between IQ (or SES) and adverse alcohol-related disease and death are not clearly defined. It could be that intelligence has effects on health through choices in lifestyle behavior or socioeconomic environment as an adult, or the relationship between intelligence and health is confounded by other factors such as biological or socioeconomic conditions early in life. As for now, we can only describe the association, but not explain it fully.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 157: A mistaken interpretation of data relating alcohol to mortality – 20 February 2015

Reference: Knott CS, Coombs N, Stamatakis E, Biddulph JP. All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts. BMJ 2015;350:h384 doi: 10.1136/bmj.h384.

The authors of this paper have carried out a regression analysis to examine the association of reported alcohol consumption with all-cause mortality, dividing their sample into different age groups. They used data from Health Survey for England 1998-2008, linked to national mortality registration data. Their published results show lower risk of mortality (hazard ratios < 1.0 for mortality in comparison with recent non-drinkers and with never drinkers) for subjects in essentially all categories of moderate drinking. However, the authors have interpreted their analyses as indicating that moderate drinking is not associated with all-cause mortality for the vast majority of the population.

Forum members, and many other scientists, have been surprised by the conclusions of the authors, who apparently did not consider basic statistical principles (such as dealing with type-2 errors) in judging their results. The investigators appear to have looked only at p-values and ignored the estimates of effect in their own data, coming to the conclusion of no association between moderate alcohol and total mortality for most age groups. Focusing only on significance testing for estimating effects has been strongly condemned by epidemiologists and statisticians and can lead to inaccurate results.

The paper reflects a gross misinterpretation of the data, not what would be expected in a publication in a leading journal. In other words, the authors’ conclusions are not backed up by their data. A more appropriate headline based on this paper would be “Study supports a moderate protective effect of alcohol against all-cause mortality.” Given the wide media coverage of this article, with striking headlines indicating that moderate drinking does not affect mortality, one Forum reviewer wondered “How can more than 30 years of research in this field be undone by one misguided paper in the BMJ? Once in a while I reflect on how some doctors and journalists interpret scientific papers; they seem to rely more on abstracts and press releases.”

The Forum considers that the conclusions of the authors of this paper are simply not supported by the data provided. Rather, their findings are in accordance with those from previous prospective studies showing that, for all age groups, moderate alcohol consumption is associated with a decrease in all-cause mortality risk.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 142: A large study of alcohol consumption and mortality — 14 July 2014

Reference: Ferrari P, Licaj I, Muller DC, et al (36 other authors). Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study. Pre-publication; BMJ Open 2014;4:e005245. doi:10.1136/bmjopen-2014-005245

The large European Prospective Investigation into Cancer and Nutrition Study (EPIC) has released a new analysis of the relation of alcohol consumption to mortality. The study concluded that alcohol use was positively associated with overall mortality, alcohol-related cancers, and violent death and injuries, but marginally to cardiovascular disease, and that absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.

There is no question that heavy alcohol consumption, especially when associated with smoking, increases the risk of a number of upper aero-digestive cancers that are commonly referred to as “alcohol-related cancers.” In the present study, the authors have also included in this group a number of other cancers that may be related less directly to the effects of alcohol; these include colorectal cancer and female breast cancer which, because they are so much more common, make up the large majority of cancers “related to alcohol.” Forum members consider the EPIC study to be an important source of data on cancer, but had a number of questions about the analysis and especially about the conclusions of the authors.

Major weaknesses of the study are that an assessment of alcohol intake was obtained only at a baseline visit, with no further assessments during a follow-up period averaging 12 years, and especially, no information was available on the pattern of drinking of subjects (e.g., regular moderate versus binge drinking). Further, Forum members noted that there was no discussion of the effects of under-reporting of alcohol, which has been shown to markedly affect health effects of alcohol intake in epidemiologic studies. In fact, recent large studies show that most of the cases of cancer that appear to relate to “light-to-moderate drinking” actually relate to underreporting of consumption by subjects who are found, from other collected medical data, to be heavy users or abusers of alcohol.

The authors focus on “extreme drinkers,” which consist of women who consume (≥30 g/day) or men who consume ≥60 g/day. They do not point out that only 2.4% of the women in this study consumed at this level, and little attention is given to the fact that almost all of the women were non-drinkers or light-moderate drinkers. From the data presented in the paper, there is a clear U-shaped curve among women: the highest risks for total mortality were in the abstainers (a 26% increase over the referent group of light drinkers) and the very small number of women in the highest drinking category (a 27% increase).

For men, 8.2% were in the highest drinking category, reporting an average consumption of ≥ 60 g/d (5 – 6 typical drinks). For men, there was generally a U-shaped curve, with lower death rates for light to moderate drinkers. However, the heaviest drinkers had the highest risk of death for overall mortality and for deaths from cancers and other causes of death. For both men and women, at every level of drinking, smokers had an increased risk of death in comparison with non-smokers.

Some reviewers were also concerned about the unusual categorization of alcohol intake used in the study. Referring to subjects reporting 0.1 – 4.9 g/day as “moderate drinkers” is a strange designation for an alcohol intake that in most other studies would be named as light or very modest, and may lead to confusion in interpreting results. (Most studies would define 5 – 14.9 g/day as light to moderate drinkers, and this group is not given a name in this study).

Overall, this study tends to show a U-shaped relation between alcohol consumption and mortality. The data presented focus primarily on the highest categories of drinking, levels that are well known to relate to many diseases and mortality. For truly light-to-moderate consumption, however, there is overwhelming epidemiologic data that such drinking relates to lower mortality risks, and the present study does not contradict such an association.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 139: Does adjustment for stress levels explain the protective effect of moderate drinking on the risk of mortality? — 18 May 2014

Reference: Ruf E, Baumert J, Meisinger C, Döring A, Ladwig K-H, and for the MONICA/KORA Investigators. Are psychosocial stressors associated with the relationship of alcohol consumption and all-cause mortality? BMC Public Health 2014, 14:312. http://www.biomedcentral.com/1471-2458/14/312.

An inverse association between moderate alcohol consumption and total mortality has been reported in most prospective epidemiologic studies, even after adjustments for all known potential confounders. The present analysis was carried out specifically to focus on the effects of psychosocial stressors on the association, using a large population-based German cohort from the WHO MONICA study. No alcohol intake was reported by 15.3% of males and 41.8% of females; “moderate drinking” was defined as an average intake of 0.1-39.9 g/day for men (making up 51.1% of the cohort) and 0.1 – 19.9 g/day for women (38.8% of the cohort). Although data are not presented, there were apparently few women in the higher drinking categories.

The authors related the effects of including, or not including, in their equations a large number of psychosocial stressors, including educational level, occupational status, several indices of social support, job strain symptoms, depressive symptoms, somatic symptoms, and self-perceived health status, in the estimation of the effects of alcohol consumption on risk of total mortality over an average follow-up period of 12 years. In their analyses, there was little effect on risk estimates for mortality when these factors were added to the multi-variable analysis. The authors conclude: “The observed protective effect of moderate drinking could not be attributed to misclassification or confounding by psychosocial stressors.”

The authors have demonstrated among men a “U-shaped” curve, with the risk for moderate drinkers being 25-30% lower than that of both non-drinkers and heavier drinkers. For women, there was a lower estimated mortality risk ratio for all drinkers than for non-drinkers, although the confidence intervals included 1.0 in all categories (perhaps, as the authors state, there were few women in their higher categories of alcohol intake).

Forum reviewers thought that this was a well-done analysis of a large population-based population. It did not support the hypothesis that social support, job strain, depressive symptoms, and other such psychosocial factors have a strong influence on the demonstrated inverse relation between moderate alcohol consumption and total mortality. Thus, this study provides additional evidence that the observed reduction in total mortality seen among moderate drinkers is not due to confounding by other lifestyle factors, including psychosocial stressors.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 135: Binge drinking greatly increases mortality risk among moderate drinkers — 11 March 2014

Reference: Holahan CJ, Schutte KK, Brennan PL, Holahan CK, Moos RH. Episodic heavy drinking and 20-year total mortality among late-life moderate drinkers. Alcohol Clin Exp Res 2014; pre-publication; DOI: 10.1111/acer.12381.

This study was based on a sample of “late-middle-aged” (55-65 years old at baseline) community residents who were recruited from the western part of the United States to participate in a study of late-life alcohol consumption and drinking problems. The present analyses evaluated association between episodic heavy drinking and total mortality among 446 adults who were considered to be “moderate” drinkers. The authors report that the 74 moderate drinkers who engaged in episodic heavy drinking (“binge drinking”) had more than two times higher odds of 20-year mortality than moderate drinkers who did not binge drink.

An association between binge drinking and health outcomes has been demonstrated in epidemiologic studies for decades. Many (but not all) studies have shown an approximately two-fold increase in the risk of adverse outcomes for binge drinkers, in comparison with moderate drinkers who do not binge drink. In reviewing the present study, Forum members commented on the small number of subjects (only 74 binge drinkers in the analysis), and some other analytic weaknesses (e.g., no data on potential changes in drinking habits over 20 years, inadequate control of some potential confounders, results not applicable to the general population as some subjects were recruited because of previous alcohol misuse). Nevertheless, the results of the study support adverse effects on mortality of such a drinking pattern.

There are now considerable scientific data indicating harmful health effects of episodic excessive drinking in terms of coronary heart disease, other diseases of ageing, and mortality. Simply knowing the average intake of subjects over a period of time is inadequate for classifying their alcohol consumption. For middle-aged and older subjects the drinking pattern that has been shown to be associated with the most favorable health outcomes (including greater longevity of life) is regular, light-to-moderate intake, especially when the alcoholic beverage is consumed with food.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 132: Pattern of alcohol consumption and cause of death in a large European prospective study — 21 January 2014

A large group of investigators participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study have reported on the association of alcohol consumption with disease-specific mortality over a 12-year period among a very large number of men and women. Alcohol intake over the past year (as well as estimates of earlier intake) was reported at baseline. A variety of approaches were used to identify deaths in the participating cohorts, but validation of the cause of death was not possible. No data were reported on certain key aspects of drinking pattern (frequency of alcohol intake, binge drinking, with meals, etc.) and beverage-specific effects were not reported.

The authors report that the risk of death from cardiovascular diseases was lower, and from cancer and certain other causes of death were higher, among drinkers than among their referent group of “lifetime light users” (men reporting ≤1 drink/week and women reporting ≤ 0.5 drinks/week). However, their graphs of alcohol intake and risk of total mortality (not included in the paper but in supplementary data they provide on the internet) show strong J-shaped curves for increasing alcohol intake for both men and women. For men, the risk among alcohol consumers of up to about 48 gr/day (the equivalent of approximately four “typical drinks”) was lower than that of the lifetime light users that made up the referent group; at higher intake, the risk increased above that of light drinkers. For women, the risk of total mortality for drinkers remained lower than that of the referent group at all reported levels of intake. Despite these findings, the entire paper focuses only on the increased risk of death from alcohol for certain diseases, and almost completely ignores the net, overall effects on total mortality.

Forum reviewers considered that while the analyses were done correctly, there were major weaknesses in the estimation of “lifetime alcohol intake,” no data on the pattern of intake, no validation of coexisting diseases and, especially, no validation of the specific cause of death, even though this was the primary outcome of the study. All of these factors weaken the strong assertions made by the authors in their conclusions.

Forum members were concerned that the authors seemed to obscure the total effects of light-to-moderate drinking (lower risk of all-cause mortality), and emphasize only the harmful effects. Some reviewers considered that the presentation appeared to be based more on ideology than on an unbiased assessment of the data, and one suggested that the paper appears to have been written starting from pre-conceived conclusions, then finding data to support them.

It is interesting that two Commentaries published with this article came to divergent views. One by Stockwell and Chikritzhs emphasized potential bias and confounding that cause concern when relating alcohol to mortality in observational studies. While they then pointed out how well the present authors adjusted for many of these factors, they nevertheless concluded their commentary repeating how such factors are difficult to control and stating that “ . . . a healthy dose of skepticism is warranted for the hypothesis that light/moderate alcohol consumption is beneficial to health.” (They do not mention that data on alcohol and mortality are far more robust that data supporting generally accepted beliefs of the beneficial effects of physical exercise, eating a healthy diet, maintaining a lean body mass, etc.)

On the other hand, the commentary on the present paper by Banks considered the data presented quite sound, and concluded: “If taken as causal, these findings are consistent with most public health advice about alcohol, except that most advice recommends an upper limit to alcohol consumption, but does not actually encourage drinking. In fact, the evidence goes further than this and indicates that, in later life, on average and bearing in mind the priorities and risks of specific individuals, drinking at least some alcohol, but not too much, is likely to minimize the overall risk of death.”

Reference: Bergmann MM, Rehm J, Klipstein-Grobusch K, et al (38 authors). The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Int J Epidemiol 2013;42:1772-1790

Attached Commentaries:

Banks E. Commentary: Lifetime alcohol consumption and mortality: have some, but not too much. Int J Epidemiol 2013;42:1790–1792; doi:10.1093/ije/dyt218

Stockwell T, Chikritzhs T. Commentary: Another serious challenge to the hypothesis that moderate drinking is good for health? Int J Epidemiol 2013;42:1792–1794; doi:10.1093/ije/dyt217

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 127: Estimation of alcohol-attributable and alcohol-preventable mortality in Denmark — 6 November 2013

Reference: Eliasen M, Becker U, Grønbæk M, Juel K, Tolstrup JS. Alcohol-attributable and alcohol-preventable mortality in Denmark: an analysis of which intake levels contribute most to alcohol’s harmful and beneficial effects. Eur J Epidemiol 2013; DOI 10.1007/s10654-013-9855-2

In an attempt to judge the harmful and beneficial health effects related to alcohol consumption, Danish scientists have carried out analyses comparing alcohol-attributable and alcohol-preventable mortality in Denmark. They have used estimates of the potentially harmful effects of alcohol use on more than 20 diseases, giving 100% values to “alcohol use disorders,” although the specific causes of death are not known for this category. Most of the other attributions for harm are realistic, but the alcohol preventable attributions for diabetes and ischemic heart disease appear to be low. The authors conclude that 5.0% of deaths among women and 9.5% of deaths among men were attributable to alcohol in Denmark in 2010, with the majority of all alcohol-attributable deaths caused by high consumption. They attribute only between 2 and 3% of deaths to be preventable by alcohol.

Previous estimates of alcohol-attributable and alcohol-preventable effects have varied widely, emphasizing the importance of the assumptions made by the investigators in any set of analyses. For example, an analysis of deaths in Germany by Konnopka et al (Konnopka A, Hans-Helmut König H-H. The health and economic consequences of moderate alcohol consumption in Germany 2002. Value in Health 2009;12:253-261) concluded that there were more alcohol-preventable deaths than alcohol-attributable deaths and a report from the UK also estimated much lower rates for alcohol-attributable deaths (White IR, Altmann DR, Nanchahal K. Mortality in England and Wales attributable to any drinking, drinking above sensible limits and drinking above lowest-risk level. Addiction 2004;99:749–756). Further, a previous report that included data for Denmark gave very different results for net alcohol effects, estimating that less than 1% of deaths were attributable to alcohol (Britton A, Nolte E, White IR, Gronbaek M, Powles J, Cavallo F, McPherson K. A comparison of the alcohol-attributable mortality in four European countries. Eur J Epidemiol. 2003;18:643–51). It is probable that different underlying assumptions of alcohol effects on various diseases are the prime reason for such differences.

There is no question that heavy alcohol consumption contributes to a large number of disease conditions, and the findings of this study emphasize the magnitude of the problem. On the other hand, if the potentially beneficial effects of moderate alcohol consumption on many common diseases are underestimated, a net unfavorable result, as in the present study, is unavoidable. It will be interesting to see what assumptions are made in other studies such as this, and how such assumptions affect the outcome of analyses.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 124: The J-shaped curve for the relation of alcohol consumption to mortality — 17 September 2013

Reference: Plunk AD, Syed-Mohammed H, Cavazos-Rehg P, Bierut LJ, Grucza RA. Alcohol consumption, heavy drinking, and mortality: Rethinking the J-shaped curve. Alcohol Clin Exp Res 2013;pre-publication: DOI: 10.1111/acer.12250

An analysis based on data from more than 110,000 subjects in the USA, of whom 3,364 died during a follow-up period of up to 9 years, was used to evaluate the relation of “heavy drinking” and “nonheavy drinking” to the risk of all-cause mortality. The authors defined heavy drinking as 5 or more drinks/occasion, and recorded the frequency in which subjects consumed such amounts. Subjects consuming < 5 drinks/occasion were classified as nonheavy drinkers.

The key findings of the analyses were that there was a positive and linear increase in risk of mortality for subjects consuming heavy amounts of alcohol, with the risk increasing as drinking at this level was more frequent. For nonheavy drinkers, there was a J-shaped relation with mortality. The point at which the nonheavy drinkers’ risk of mortality exceeded that of abstainers was between 4 and 5 drinking occasions/week.

Forum reviewers thought that this was a well-done analysis that emphasizes the importance of the pattern of drinking, and not just the average weekly intake. Although the upper limits of drinks/occasion exceeded that usually considered as “moderate,” a J-shaped curve between alcohol and mortality for these drinkers was demonstrated. This is the pattern usually seen in prospective epidemiologic studies when “moderate” is defined at somewhat lower levels of alcohol intake.

Forum reviewers agreed with the conclusions of the authors regarding the importance of considering the pattern of drinking when evaluating the health effects of alcohol. The authors concluded: “Promoting less harmful drinking patterns by reducing heavy drinking frequency is an appropriate harm reduction strategy, and assessing drinking pattern by determining the frequency of heavy and nonheavy drinking is a simple and fast way to determine risk and promote less risky drinking behavior.”

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 097: Per-capita alcohol intake and all-cause mortality in Australia — 4 December 2012

Reference: Livingston M, Wilkinson C. Per-capita alcohol consumption and all-cause male mortality in Australia, 1911–2006. Alcohol and Alcoholism 2012. Pre-publication: doi: 10.1093/alcalc/ags123

An ecologic analysis from a group in Australia has related trends in the per-capita consumption of alcohol in Australia with rates of all-cause mortality. Unfortunately, the authors do not have data on individual consumption of alcohol (and no way of knowing if the people who drink or do not drink are those who die) and do not have data on many key factors that relate to both alcohol consumption and mortality (e.g., education, income, diet, occupation, etc.). Especially, they have no data on the patterns of consumption of members of the population (regular moderate intake or binge drinking). They “adjust” for death rates in women but do not report sex-specific mortality rates.

This paper illustrates many of the dangers of the so-called “ecologic fallacy,” in which comparisons are made between aggregate population data and biologic outcomes. It has been shown that such comparisons may be of interest in generating hypotheses, but not for answering questions of causation, for which different types of studies are required. As stated in a leading textbook of epidemiology: “Ecologic analysis poses major problems of interpretation when making ecologic inferences and especially when making biologic inferences. In contemporary epidemiology, the ‘ecologic fallacy’ reflects the failure of the investigator to recognize the need for biologic inference and thus for individual-level data. This need arises even when the primary exposure of interest is an ecologic measure and the outcome of interest is the health status of entire populations.”

With such serious limitations from the use of ecologic comparisons, this paper does not provide data upon which alcohol policy can be based. The authors of this paper appear to have ignored previous research providing very different interpretations of an inverse association between per-capita alcohol intake and mortality. A plethora of studies based on alcohol intake among individuals, and especially patterns of consumption, provide data needed for such policy decisions.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 065: Are there differences in mortality between people consuming wine and those consuming other types of alcoholic beverages? – 20 December 2011

Wine consumers, especially in comparison with spirits drinkers, have been shown to have higher levels of education and income, to consume a healthier diet, be more physically active, and have other characteristics that are associated with better health outcomes. However, epidemiologic studies have been inconsistent in showing that, after adjustment for all associated lifestyle factors, consumers of wine have lower risk of cardiovascular disease and mortality than do consumers of other beverages.

A study based on the long-term follow up of a group of older Americans concluded that the associated lifestyle habits and environmental factors of wine consumers largely explained their better health outcomes. Forum reviewers were concerned about some of the methodological approaches used, and believed that the data presented in the paper were inadequate to support such a conclusion. This was a small study, had only a single estimate of alcohol intake (at baseline but not throughout 20 years of follow up), and the authors may have over-adjusted for large differences in lifestyle factors between what they termed as “low-wine” and “high-wine” consumers. The study did confirm a lower mortality risk for alcohol consumers than for non-drinkers.

Experimental studies have clearly indicated that the polyphenols and other constituents that are present in wine and some beers have independent protective effects against most cardiovascular risk factors. Whether or not such advantages are seen among moderate drinkers of wine (or beer) in epidemiologic studies is difficult to determine, as comparisons are not being made between wine, beer, and spirits but between humans who consume one or other such beverage. In almost all populations, drinkers of a specific beverage differ in many ways other than just the type of beverage they consume.

Reference: Holahan CJ, Schutte KK, Brennan PL, North RJ, Holahah CK, Moos BS, Moos RH. Wine consumption and 20-year mortality among late-life moderate drinkers. J Stud Alcohol Drug 2012; 73: 80–88.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research, please click here.

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

The author of this paper 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 (CHD). 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. He concludes that the so-called “errors” have not led to erroneous results, and that there is a strong protective effect of moderate drinking on CHD and all-cause mortality.

The results of this analysis support the vast majority of recent well-done prospective studies. In the present 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.

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

For the full review of this publication by members of the International Scientific Forum on Alcohol Research, please click here.

Critique 017. Moderate alcohol intake is associated with a lower risk of total mortality than are either abstinence or heavy drinking. 5 September 2010

Reference: Holahan CJ, Schutte KK, Brennan PL, Holahan CK, Moos BS, Moos RH. Late-Life Alcohol Consumption and 20-Year Mortality. Alcoholism: Clinical and Experimental Research 2010;34:in press, November 2010.

In a study based on data from 1,824 predominantly Caucasian Americans from the Western part of the United States, alcohol consumption at baseline was related to mortality risk during a 20-year follow-up period. Subjects were recruited into a longitudinal project that has examined late-life patterns of alcohol consumption and drinking problems. Lifetime abstainers were not included in the study, which focused on stress and coping processes among problem drinkers and non-problem drinkers. The sample at baseline included only subjects aged 55 to 65 years who had had outpatient contact with a health care facility in the previous 3 years.

The database at baseline included information on daily alcohol consumption, sociodemographic factors, former problem drinking status, health factors, and social-behavioral factors. Subjects who were not lifetime abstainers but did not report drinking at the time of the baseline examination were classified as “abstainers.” Data on potential changes in alcohol consumption during the course of the study were not collected. Death during follow up was confirmed primarily by death certificate.

The key results of the paper are that even when adjusting for sociodemographic factors, former problem drinking status, health factors, and social-behavioral factors, moderate drinking was associated with considerably lower risk of all-cause mortality. In comparison with “moderate drinkers” (subjects reporting up to 3 drinks/day), abstainers had 51% higher mortality risk and heavy drinkers had 45% higher risk. The study supports most previous scientific studies showing that moderate drinking, in comparison with both abstinence and heavy drinking, is associated with lower risk of total mortality.

For the detailed critique of this paper by the International Scientific Forum on Alcohol Research, click here.

Critique 012. Moderate drinking in the elderly is associated with lower total mortality. 23 July 2010

Reference: McCaul KA, Almeida OP, Hankey GJ, Jamrozik K, Byles JE, Flicker L. Alcohol use and mortality in older men and women. Addiction 2010. On-line prior to publication: doi:10.1111/j.1360-0443.2010.02972.x

The effects of alcohol consumption in the elderly may be modified by a decreased ability to metabolize alcohol, an altered volume of distribution due to reduced lean body mass and total body water, and an increased prevalence of co-morbid conditions. These factors make this study of the net effects of drinking among a large number of community-dwelling elderly men and women especially important.

In large prospective studies from Australia of men aged 60-79 and women aged 70-75 years of age, men consuming up to 4 drinks/day and women up to 2 drinks/day had considerably lower risk of dying (total mortality) than did non-drinkers. For subjects reporting 1-2 drinks/day, their total mortality risk was about 20-30% lower than that of abstainers.

While the authors concluded that not consuming alcohol on 1 or 2 days per week was associated with better outcomes, this conclusion is not in accordance with their own data. The benefit of one or two “alcohol-free” days per week has never been substantiated with solid evidence from any large epidemiological study.

Our Forum review concludes that in terms of total mortality risk, recommendations for very low levels of drinking among the elderly may be overly restrictive, as this study showed lower total mortality for up to 4 drinks/day for elderly men and 2 drinks/day for elderly women. Further, this study does not provide support for the conclusion that mortality is lower for people who have 1 or 2 “alcohol-free” days per week.

For the full critique of this paper by the International Scientific Forum on Alcohol Research, click here