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Alcohol, heart health and risk of dying (mortality) - A summary of clinical evidence

dead body.

The debate about alcohol and health benefits, the J-Shaped Curve and "Sick Quitter" Hypothesis

There has been consistent evidence in large scale clinical trials that moderate consumption of alcoholic drinks reduces the risk of dying prematurely versus being an abstainer - the so called J-shaped curve.

However, some have argued that the benefits are only applicable to a minority e.g. Knot et al 2015, BMJ "Compared with never drinkers, age stratified analyses suggest that beneficial dose-response relations between alcohol consumption and all cause mortality may be largely specific to women drinkers aged 65 years or more, with little to no protection present in other age-sex groups.". 

The paper says "The J-shaped relation is contentious, however, with some arguing that protective effects may be confounded by the common classification of heterogeneous non-drinking groups into a single referent category. Specifically, former drinkers have been found to exhibit poorer self reported health,higher levels of depression,and increased risk of mortality than never drinkers. As such, protective associations identified among light drinkers may be less a consequence of a beneficial biological mechanism and more a statistical artefact resulting from the application of a pooled non-drinking category. Indeed, when former drinkers were excluded from meta-analysis,the protective effect between alcohol consumption and total mortality was attenuated (P<0.01). Such a finding suggests that protective effects may have been over-estimated by existing studies."

Critics of the 2015 study point out that because the authors gathered data which clearly showed health benefits from moderate drinking and then divided it into so many subgroups that it was almost impossible for them to produce statistically significant results. In the end the only people who appeared to benefit from drinking were post-menopausal women.

The proponents of the "sick quitter" hypothesis that state that endorse the idea that teetotallers are more than those who do drink because they are chronically ill or because they are ex-alcohol drinkers and have damaged their bodies with alcohol. They argue that alcohol doesn't protect health its just that teetotallers are unusually sickly.

Rimm EB et al 2007, "Alcohol and Coronary Heart Disease: Drinking Patterns and Mediators of Effect" took on the "sick quitter" hypothesis saying "A recent meta-analysis raised questions about systematic misclassification error in observational studies because of inclusion among “non drinkers” of ex-drinkers and/or occasional drinkers. However, misclassification among a small percentage of non drinkers cannot fully explain the inverse relation, and there is substantial evidence to refute the “sick quitter” hypothesis. Furthermore, it has been shown that moderate alcohol consumption reduces CHD and mortality in individuals with hypertension, diabetes, and existing CHD. To address the issue of residual confounding by healthy lifestyle in drinkers, in a large prospective study we restricted analysis to only “healthy” men (who did not smoke, exercised, ate a good diet, and were not obese). Within this group, men who drank moderately had a relative risk for CHD of 0.38 (95% CI, 0.16–0.89) compared with abstainers, providing further evidence to support the hypothesis that the inverse association of alcohol to CHD is causal, and not confounded by healthy lifestyle behaviors."

There was further controversy when Stockwell et al published a new study in the March 2016 issue of the Journal of Studies on Alcohol and Drugs, "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality."

The new study was a systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. A total of 87 studies were examined.

Tim Stockwell, Ph.D., the lead researcher on the analysis and director of the University of Victoria's Centre for Addictions Research in British Columbia, Canada said that "Most often, studies have compared moderate drinkers (people who have up to two drinks per day) with "current" abstainers. The problem is that this abstainer group can include people in poor health who've cut out alcohol. A fundamental question is, who are these moderate drinkers being compared against?"

The paper concluded that when his team corrected for those abstainer "biases" and certain other study-design issues, moderate drinkers no longer showed a longevity advantage. Further, only 13 of the 87 studies avoided biasing the abstainer comparison group--and these showed no health benefits. It stated that "Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health."

Further reading on the J-Curve debate
Eric Crampton "Moderate drinking and health"

Eric Crampton "he J-Curve: science vs politics"

Christopher Snowdon "Teetotallers die younger, don't let 'em fool you"

Key studies Alcohol,cardiovascular protection and mortality

Meta Analysis and summary studies

Rimm EB 1996, "Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits" reporting "Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found an association for beer, and four for spirits.

Rimm concluded "Results from observational studies, where alcohol consumption can be linked directly to an individual's risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink."

Rimm EB et al 1999 in "Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors" reported that "61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease." and they concluded that "Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors"

Iestra JA 2005 in "Effect size estimates of lifestyle and dietary changes on all-cause mortality in coronary artery disease patients: a systematic review" presented " A literature search was performed on the effect of lifestyle and dietary changes on mortality in CAD patients. Prospective cohort studies and randomized controlled trials of patients with established CAD were included if they reported all-causes mortality and had at least 6 months of follow-up. The effect estimates of smoking cessation (relative risk [RR], 0.64; 95% CI, 0.58 to 0.71), increased physical activity (RR, 0.76; 95% CI, 0.59 to 0.98), and moderate alcohol use (RR, 0.80; 95% CI, 0.78 to 0.83) were studied most extensively. For the 6 dietary goals, data were too limited to provide reliable effect size estimates. Combinations of dietary changes were associated with reduced mortality (RR, 0.56; 95% CI, 0.42 to 0.74)."

Di Castelnuovo et al 2006 "Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies" used a meta analysis technique where the results of 34 studies were collated and reviewed. The study looked at the link between alcohol dose and mortality in both sexes in clinical trials conducted before the end of 2005 with over 1 million subjects. The scale of the overall analysis is therefore impressive.

The study reported that "A J-shaped relationship between alcohol and total mortality was confirmed in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality or the chance of dying, maximum protection being 18% in women and 17% in men Higher doses of alcohol were associated with increased chances of dying with women having a lower level than men before the chances of dying increased. ".

Concluding that "Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival."

Patra J et al 2010 "Alcohol consumption and the risk of morbidity and mortality for different stroke types--a systematic review and meta-analysis" reported "The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity." and concluded that "These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed."

Ronksley PE  2011 "Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis" reported "The pooled adjusted relative risks for alcohol drinkers relative to non-drinkers in random effects models for the outcomes of interest were 0.75 (95% confidence interval 0.70 to 0.80) for cardiovascular disease mortality (21 studies), 0.71 (0.66 to 0.77) for incident coronary heart disease (29 studies), 0.75 (0.68 to 0.81) for coronary heart disease mortality (31 studies), 0.98 (0.91 to 1.06) for incident stroke (17 studies), and 1.06 (0.91 to 1.23) for stroke mortality (10 studies). Dose-response analysis revealed that the lowest risk of coronary heart disease mortality occurred with 1-2 drinks a day, but for stroke mortality it occurred with ≤1 drink per day. Secondary analysis of mortality from all causes showed lower risk for drinkers compared with non-drinkers (relative risk 0.87 (0.83 to 0.92))."

They concluded  "Light to moderate alcohol consumption is associated with a reduced risk of multiple cardiovascular outcomes."

Costanzo S 2011 "Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis" reported "previous studies evaluating whether different alcoholic beverages would protect against cardiovascular disease, a J-shaped relationship for increasing wine consumption and vascular risk was found; however a similar association for beer or spirits could not be established. An updated meta-analysis on the relationship between wine, beer or spirit consumption and vascular events was performed. Articles were retrieved through March2011 by PubMed and EMBASE search and a weighed least-squares regression analysis pooled data derived from studies that gave quantitative estimation of the vascular risk associated with the alcoholic beverages. From 16 studies, evidence confirms a J-shaped relationship between wineintake and vascular risk. A significant maximal protection-average 31% (95% confidence interval (CI): 19-42%) was observed at 21 g/day of alcohol. Similarly, from 13 studies a J-shaped relationship was apparent for beer (maximal protection: 42% (95% CI: 19-58%) at 43 g/day of alcohol). From 12 studies reporting separate data on wine or beer consumption, two closely overlapping dose-response curves were obtained (maximal protection of 33% at 25 g/day of alcohol). This meta-analysis confirms the J-shaped association between wine consumption and vascular risk and provides, for the first time, evidence for a similar relationship between beer and vascular risk. In the meta-analysis of 10 studies on spirit consumption and vascular risk, no J-shaped relationship could be found."

Krenz et al in the 2012 review, "Moderate ethanol ingestion and cardiovascular protection: From epidemiologic associations to cellular mechanisms" said the following:

"Abundant epidemiologic evidence and the results interventional mechanistic studies conducted in animal models and cell culture systems strongly support the notion that antecedent ethanol exposure at moderate levels confers protective cardiovascular effects."

"Given the well-established pathologic effects of heavy drinking, wine lovers world-wide no doubt rejoiced when large-scale epidemiological studies first emerged showing that regular consumption of light to moderate amounts of alcoholic beverages, in particular red wine, was associated with a cardio-protective effect. One of the first studies showing a significant negative association between alcohol consumption and the risk of a subsequent first myocardial infarction that was well-controlled for cigarette smoking and other risk factors was published in 1974 . Over the following 4 decades, numerous epidemiological studies including several meta-analyses have consistently reported that an average alcohol consumption in the range of 0.5 to 2 standard drinks per day reduces coronary heart disease-related risks and ischemic stroke compared to non-drinkers."

"Interestingly, initial work suggested that the protective effects associated with light to moderate intake of alcoholic beverages may be due to the polyphenols in grapes, wine, and dark beer. In particular, the stilbene resveratrol has been a major focus of research interest because this and other red wine constituent polyphenols exert powerful antioxidant actions, upregulate eNOS gene expression, enhance NO production and have been found to reduce morbidity and mortality due to cardiovascular disease. In the human diet, red wine is one of the richest sources of polyphenols and moderate red wine drinkers consume these compounds at levels well above the population average. Despite the demonstrated protective actions of resveratrol and flavonoids, discrimination between the effects of these red wine constituent polyphenols versus ethanol per se to induce protection associated with consumption of alcoholic beverages is controversial, in part owing to low levels of the former achieved in the blood following red wine ingestion. Indeed, flavonoids and other wine polyphenols are extensively metabolized during absorption, resulting in formation of glucuronidated, sulfated, and methylated derivatives of the parent polyphenol, which have not been extensively evaluated for their protective effects. As a consequence, the highest plasma concentrations achieved after ingestion of resveratrol-rich beverages by humans range between 1 and 10 μM. These concentrations are lower than those typically evaluated in cell culture models and in animal studies. To further complicate the distinction between ethanol- and resveratrol-specific effects, the downstream molecular mechanisms so far identified for the two compounds show substantial overlap."

"Some epidemiological studies have shown that consumption of red wine is more protective than other types of alcohol, whereas other studies failed to identify an additional advantage associated with red wine."

"The health effects of ethanol are dependent on the amount of alcohol consumed and the pattern of intake. Nearly all epidemiologic studies report a J-shaped curve, whereby light to moderate ethanol consumption (1-2 standard drinks per day) exhibit less risk for adverse cardiovascular events and overall mortality than abstainers, while heavy drinkers (3-4 or more drinks per day) demonstrate increased risk. As with liver injury induced by ethanol, this varies by sex, with women benefiting from 1 standard drink per day, whereas daily consumption of 1-2 drinks by males was associated with reduced total mortality. On the other hand, increased mortality occurs in females with daily intake of 2 or more alcohol beverages and in men consuming more than 3 drinks per day."

"The effects of light to moderate ethanol consumption appear to be most clearly related to cardiovascular benefits, with most studies reductions in risk for heart disease by 30-35% Regular alcohol consumption at low to moderate levels is associated with significant reductions in the incidence of myocardial infarction in both males and females, regardless of age in adults. Importantly, this effect was noted in higher risk populations, including individuals with diabetes, hypertension, hypercholesterolemia, known heart disease, or who are overweight, as well as in cigarette smokers."

"Cardiovascular disease risk is also lowered by moderate ethanol consumption in individuals adhering to healthy lifestyle behaviors. Indeed, it has been reported that men who exercised regularly for at least 30 min/day, abstained from smoking, adhered to a healthy diet, and maintained their body mass index at less than 25 kg/m2 derived a health benefit from regular alcohol intake at moderate levels, demonstrating a 40-50% reduction in risk for myocardial infarction. Moderate wine drinking also appears to strengthen the cardioprotective effects of fish consumption, an observation that links two important components of the Mediterranean diet, namely omega-3 fatty acids and wine."

In addition to reducing the incidence and severity of myocardial infarction, low to moderate alcohol consumption is also associated with lower risk for ischemic stroke, dementia, congestive heart failure, peripheral artery disease, intestinal and hepatic I/R injury, and frequency of Raynaud’s phenomenon."

"Although the concept that moderate intake of ethanol exerts protective effects in the cardiovascular system is now well accepted, important issues have been raised which challenge this premise. For example, it has been argued that uncontrolled confounding influences by lifestyle factors may play a role in the association between moderate alcohol intake and cardiovascular risk. Some work has led to the suggestion that individuals who regularly consume alcohol beverages exhibit healthier habits with regard to diet and/or exercise and enjoy superior sociodemographic factors, which could explain the reduced risk for ischemic myocardial disease . However, systematic review and meta-analysis of interventional studies directed at the association between alcohol consumption and disease markers associated with risk for cardiovascular disease in adults without known cardiovascular disease argues against this supposition, as do the results of studies designed to better control for confounding sociodemographic factors and differences in dietary patterns and exercise adherence.

"While the association between alcohol consumption and decreased cardiovascular risk is clear, it remains uncertain as to whether these correlative findings imply causation. However, a number of points regarding the aforementioned epidemiologic findings suggest that the association may indeed represent a cause-and-effect relationship. First, there is a temporal relation between alcohol use and prevention of cardiovascular disease. Second, greater protection is observed with increasing ethanol dose over the protective range of alcohol intake. Third, the protective association between ethanol consumption and adverse cardiovascular events has been consistently observed in diverse patient populations and in both men and women. Fourth, the reduction in risk remains significant even after the influences of potential confounders such as cigarette smoking, diet, and exercise are factored into the analysis. Fifth, the association is specific for lowering rates of cardiovascular disease but does correlate with protection in other conditions such as cancer. Finally, the coupling of the aforementioned epidemiologic associations with the interventional mechanistic studies discussed below, provides compelling support for the notion that ethanol intake may indeed confer protection against the deleterious effects of I/R."

Chiva-Blanch G 2013 "Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies" stated "Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seems to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects." and " In conclusion, wine and beer (but especially red wine) seem to confer greater cardiovascular protection than spirits because of their polyphenolic content. However, caution should be taken when making recommendations related to alcohol consumption."

Knot et al 2015, "All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts" reported that "In unadjusted models, protective effects were identified across a broad range of alcohol usage in all age-sex groups. These effects were attenuated across most use categories on adjustment for a range of personal, socioeconomic, and lifestyle factors. After the exclusion of former drinkers, these effects were further attenuated. Compared with self reported never drinkers, significant protective associations were limited to younger men (50-64 years) and older women (≥65 years). Among younger men, the range of protective effects was minimal, with a significant reduction in hazards present only among those who reported consuming 15.1-20.0 units/average week (hazard ratio 0.49, 95% confidence interval 0.26 to 0.91) or 0.1-1.5 units on the heaviest day (0.43, 0.21 to 0.87). The range of protective effects was broader but lower among older women, with significant reductions in hazards present ≤10.0 units/average week and across all levels of heaviest day use. Supplementary analyses found that most protective effects disappeared where calculated in comparison with various definitions of occasional drinkers."

The authors concluded that "Beneficial associations between low intensity alcohol consumption and all cause mortality may in part be attributable to inappropriate selection of a referent group and weak adjustment for confounders. Compared with never drinkers, age stratified analyses suggest that beneficial dose-response relations between alcohol consumption and all cause mortality may be largely specific to women drinkers aged 65 years or more, with little to no protection present in other age-sex groups. These protective associations may, however, be explained by the effect of selection biases across age-sex strata."

 Stockwell et al published a new study in the March 2016 issue of the Journal of Studies on Alcohol and Drugs, "Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality."

The new study was a systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. A total of 87 studies were examined.

They reported that  "Without adjustment, meta-analysis of all 87 included studies replicated the classic J-shaped curve, with low-volume drinkers (1.3-24.9 gethanol per day) having reduced mortality risk (RR = 0.86, 95% CI [0.83, 0.90]). Occasional drinkers (<1.3 g per day) had similar mortality risk (RR = 0.84, 95% CI [0.79, 0.89]), and former drinkers had elevated risk (RR = 1.22, 95% CI [1.14, 1.31]). After adjustment for abstainer biases and quality-related study characteristics, no significant reduction in mortality risk was observed for low-volume drinkers (RR = 0.97, 95% CI [0.88, 1.07]). Analyses of higher-quality bias-free studies also failed to find reduced mortality risk for low-volume alcohol drinkers. Risk estimates for occasional drinkers were similar to those for low- and medium-volume drinkers."

Stockwell concluded that "Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health."

Individual studies

Klatsky AL in 1992 "Alcohol and mortality" reported that "Heavier drinkers were at greater risk for death from noncardiovascular causes (relative risk at ≥ 6 drinks per day compared with no alcohol = 1.6, 95% Cl, 1.3 to 2.0) especially cirrhosis, unnatural death, and tobacco-related cancers. This alcohol-associated risk was higher in women (relative risk for death from all causes at ≥ 6 drinks per day = 2.2; Cl, 1.4 to 3.8) and younger persons (for persons < 50 years of age, relative risk for death from all causes at ≥ 6 drinks per day = 1.9; Cl, 1.3 to 2.9). Lighter drinkers were at lower risk for death from cardiovascular disease, especially coronary heart disease (relative risk at 1 to 2 drinks per day = 0.7; Cl, 0.6 to 0.9), independent of baseline risk, with the greatest reduction of risk in older persons. Lighter drinkers over 60 years of age also had a slightly lower risk for noncardiovascular death, but this finding was not independent of baseline coronary heart disease risk.

He concluded that  "Women and younger persons appear more susceptible to the increased mortality risk of heavy drinking. The reduced cardiovascular risk of lighter drinkers is more pronounced in older persons. Lower coronary disease prevalence may reduce the noncardiovascular mortality risk of lighter drinkers."

Doll R et al 1994, "Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors" reported that "Men were divided on the basis of their response to the 1978 questionnaire into two groups according to whether or not they had ever had any type of vascular disease, diabetes, or "life threatening disease" and into seven groups according to the amount of alcohol they drank. By 1991 almost a third had died. All statistical analyses of mortality were standardised for age, calendar year, and smoking habit. There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk; those who reported drinking 8-14 units of alcohol a week (corresponding to an average of one to two units a day) had the lowest risks. The causes of death were grouped into three main categories: "alcohol augmented" causes (6% of all deaths: cirrhosis, liver cancer, upper aerodigestive (mouth, oesophagus, larynx, and pharynx) cancer, alcoholism, poisoning, or injury), ischaemic heart disease (33% of all deaths), and other causes. The few deaths from alcohol augmented causes showed, at least among regular drinkers, a progressive trend, with the risk increasing with dose. In contrast, the many deaths from ischaemic heart disease showed no significant trend among regular drinkers, but there were significantly lower rates in regular drinkers than in non-drinkers. The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality. Similar differences persisted irrespective of a history of previous disease, age (under 75 or 75 and older), and period of follow up (first five and last eight years). Some, but apparently not much, of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers.

Doll concluded that "The consumption of alcohol appeared to reduce the risk of ischaemic heart disease, largely irrespective of amount. Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week. Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol, or the consumption of substantial amounts. Above about three units (two American units) of alcohol a day, progressively greater levels of consumption are associated with progressively higher all cause mortality."

Grønbaek M et al 2005, "Mortality associated with moderate intakes of wine, beer, or spirits." reported that "The risk of dying steadily decreased with an increasing intake of wine--from a relative risk of 1.00 for the subjects who never drank wine to 0.51 (95% confidence interval 0.32 to 0.81) for those who drank three to five glasses a day. Intake of neither beer nor spirits, however, was associated with reduced risk. For spirits intake the relative risk of dying increased from 1.00 for those who never drank to 1.34 (1.05 to 1.71) for those with an intake of three to five drinks a day. The effects of the three types of alcoholic drinks seemed to be independent of each other, and no significant interactions existed with sex, age, education, income, smoking, or body mass index. Wine drinking showed the same relation to risk of death from cardiovascular and cerebrovascular disease as to risk of death from all causes. "

They concluded that "Low to moderate intake of wine is associated with lower mortality from cardiovascular and cerebrovascular disease and other causes. Similar intake of spirits implied an increased risk, while beer drinking did not affect mortality."

Thun et al 1997 "Alcohol consumption and mortality among middle-aged and elderly U.S. adults" reported "Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers, with little relation to the level of consumption. The overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk."

Thun concluded "In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco."

Leong et al in 2014 "Patterns of Alcohol Consumption and Myocardial Infarction Risk: Observations from 52 Countries in the INTERHEART Case-Control Study" reported " We included 12,195 cases of first MI and 15,583 age- and sex-matched controls from 52 countries. Current alcohol use was associated with a reduced risk of MI (compared to non-users, adjusted odds ratio 0.87; 95% CI 0.80-0.94, p=0.001), however the strength of this assocation was not uniform across different regions (region-alcohol interaction p<0.001). Heavy episodic drinking (≥6 drinks) within the preceding 24 hours was associated with an increased risk of MI (odds ratio 1.4; 95% CI 1.1-1.9, p=0.01). This risk was particularly elevated in older individuals (for age >65 years, odds ratio 5.3; 95% CI 1.6-18, p=0.008).".

They concluded that "In most participants, low levels of alcohol use are associated with a moderate reduction in the risk of MI, however the strength of this association may not be uniform across different countries. An episode of heavy drinking is associated with an increased risk of acute MI in the subsequent 24 hours, particularly in older individuals."

Gaziano JM et al 2000 "Light-to-moderate alcohol consumption and mortality in the physicians’ health study enrollment cohort" reported that "There were 3,216 deaths over 5.5 years of follow-up. We observed a U-shaped relationship between alcohol consumption and total mortality. Compared with rarely/never drinkers, consumers of 1, 2 to 4 and 5 to 6 drinks per week and 1 drink per day had significant reductions in risk of death (multivariate relative risks [RRs] of 0.74, 0.77, 0.78 and 0.82, respectively) with no overall benefit or harm detected at the ≥2 drinks per day level (RR = 0.95; 95% confidence interval (CI), 0.79 to 1.14). The relationship with CVD mortality was inverse or L-shaped with apparent risk reductions even in the highest category of ≥2 drinks per day (RR = 0.76; 95% CI, 0.57 to 1.01). We found no clear harm or benefit for total or common site-specific cancers. For remaining other cancers, there was a non-significant 28% increased risk for those consuming ≥2 drinks per day."

The study concluded "These data support a U-shaped relation between alcohol and total mortality among light-to-moderate drinking men. The U-shaped curve may reflect an inverse association for CVD mortality, no association for common site-specific cancers and a possible positive association for less common cancers."

Grønbaek M 2000 "Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer" stated that "During 257 859 person-years of follow-up, 4833 participants died. J-shaped relations were found between total alcohol intake and mortality at various levels of wine intake. Compared with nondrinkers, light drinkers who avoided wine had a relative risk for death from all causes of 0.90 (95% CI, 0.82 to 0.99) and those who drank wine had a relative risk of 0.66 (CI, 0. 55 to 0.77). Heavy drinkers who avoided wine were at higher risk for death from all causes than were heavy drinkers who included wine in their alcohol intake. Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non-wine drinkers (P = 0.007 and P = 0.004, respectively)."

The authors concluded "Wine intake may have a beneficial effect on all-cause mortality that is additive to that of alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer."

In 2004, Britton, "Different measures of alcohol consumption and risk of coronary heart disease and all-cause mortality: 11-year follow-up of the Whitehall II Cohort Study" reported "A U-shaped relationship was found between volume of alcohol consumed per week and outcome. Compared to those who drank moderately (10-80 g alcohol per week), non-drinkers and those drinking more than 248 g per week had approximately a twofold increased risk of mortality. The optimal frequency of drinking was between once or twice a week and daily, after adjustment for average volume consumed per week. Those drinking twice a day or more had an increased risk of mortality (male hazard ratio 2.44 95% CI 1.31-4.52) compared to those drinking once or twice a week. Drinking only once a month or only on special occasions had a 50% increased risk of mortality. The usual amount consumed per drinking session was not indicative of increased health risk in this cohort."

They concluded that "Epidemiological studies should collect information on frequency of drinking in addition to average volume consumed in order to inform sensible drinking advice."

Buelens JW 2007 "Alcohol consumption and risk for coronary heart disease among men with hypertension" reported that "During follow-up, 653 patients with MI were documented. Compared with patients abstaining from alcohol, the haz-
ard ratio for participants with MI consuming 0.1 to 4.9 grams of alcohol per day was 1.09 (95% CI, 0.86 to 1.37); consuming 5 to 9.9 grams of alcohol per day was 0.81 (CI, 0.60 to 1.08 g/d); consuming 10 to 14.9 grams of alcohol per day was 0.68 (CI, 0.51 to 0.91 g/d); consuming 15 to 29.9 grams of alcohol per day was 0.72 (CI, 0.54 to 0.97 g/d); consuming 30 to 49.9 grams of alcohol per day was 0.67 (CI, 0.48 to 0.94 g/d); and consuming 50 ormore grams of alcohol per day was 0.41 (CI, 0.22 to 0.77 g/d) (P0.001 for trend). Associations were similar for fatal and non-fatal MI. Alcohol consumption was not associated with total death or death due to CVD. Risks for total and ischemic stroke for patients consuming 10 to 29.9 g of alcohol per day were 1.40 (CI,0.93 to 2.12) and 1.55 (CI, 0.90 to 2.68) compared with that of
abstainers. When corrected for measurement error in alcohol consumption, dietary variables, and body mass index, the hazard ratio for participants with MI per 12.5 grams per day increment of alcohol intake was 0.68 (CI, 0.46 to 1.00).

They concluded that "In this population of men with hypertension, moderate alcohol consumption was associated with a decreased risk for MI but not with risks for total death or death due to CVD. As in the general population, men with hypertension who drink moderately and safely may not need to change their drinking habits."

Holahan CJ et al 2012, "Wine Consumption and 20-Year Mortality Among Late-Life Moderate Drinkers" reported "After adjusting for all covariates, both high-wine-consumption and low-wine-consumption moderate drinkers showed reduced mortality risks compared with abstainers. Further, compared with moderate drinkers for whom a high proportion of ethanol came from wine, those for whom a low proportion of ethanol came from wine were older, were more likely to be male, reported more health problems, were more likely to be tobacco smokers, scored lower on socioeconomic status, and (statistical trend) reported engaging in less physical activity. Controlling only for overall ethanol consumption, compared with moderate drinkers for whom a high proportion of ethanol came from wine, those for whom a low proportion of ethanol came from wine showed a substantially increased 20-year mortality risk of 85%. However, after controlling for all covariates, the initial mortality difference associated with wine consumption was no longer significant."

Holahan concluded "Among older adults who are moderate drinkers, the apparent unique effects of wine on longevity may be explained by confounding factors correlated with wine consumption."