This important study reaffirms message of little and often rather than occasional drinking or binge drinking as cardio protective for both men and women.
A new paper published in Addiction by Jurgen Rehm et al studies the cardio protective association of alcohol and heart disease. Rehm states “Based on our meta-analysis, some form of a cardio protective association for IHD morbidity and mortality is hard to deny, given epidemiological evidence’”.
The pooling of studies found that the nadir (maximum cardio-protective association) for mortality and morbidity in men was located at average intake between 33 and 69 g/day, showing a significant effect in both the fractional polynomial and categorical analysis. The authors note that consumption at these levels are by no means safe from a clinical and public health perspective as they have been shown to be associated detrimentally with many other disease outcomes,. Rehm et al say a protective effect at levels of one or two drinks a day cannot be presumed for all population and that sex, pattern of drinking (binge drinking negates cardio protective effects but could not be analysed in this study). Protective effects for women were higher as women age, but more incidences of ischemic heart disease occur at this time.
’The findings from this study support current low-risk drinking guidelines, if these recognize lower drinking limits for women. If one takes into account only average volume, this study showed that most of the cardio protective effect can already be achieved with one to two drinks/day for men and one drink/day for women’. (A drink in Canada is 14g).
Higher average consumption should be discouraged because of the negative effects on many other disease outcomes. Furthermore, very low consumption levels, such as below one to two drinks per week, do not seem to confer substantial cardio protective effects.
However, at the same time, it seems that this does not apply to all drinkers and that other determinants of the alcohol effect on heart disease that were not captured by average consumption as an exposure measurement, such as drinking patterns, might play an important role. Given the negative impact of heavy drinking occasions on heart disease and injuries, low risk drinking guidelines should also include limits of drinks per occasion.
Source: The cardio-protective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Michael Roerecke1,2 & Jürgen Rehm1,2,3 (1 Centre for Addiction and Mental Health, Toronto, Canada, 2 Dalla Lana School of Public Health, University of Toronto, Canada and 3 Technische Universität Dresden, Germany).
Tim Stockwell wrote a commentary on Rehm’s finding in the same publication, to which Dr Erik Skovenborg has written the following response.
A comment on the state of the science on moderate drinking and health
Welcome, Tim Stockwell, to the rough world of nutritional epidemiology. Diet is a key modifiable risk factor in the prevention and risk reduction of coronary heart disease. As Hippocrates (460–377 BC), the father of Western medicine, put it: ‘If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health”. Nutritional epidemiology is a young discipline studying weak associations with the blunt instrument of measuring diet as an exposure. Diet and physical activity are arguably the most difficult exposures to assess in observational research and are plagued by considerable measurement error. (Michels KB. Nutritional epidemiology - past, present, future. Int J Epidemiol 2003;32:486-88). Tim Stockwell finds the state of the science on moderate drinking and health in a bad state with no high-quality evidence of significant health benefits from moderate drinking in a commentary to a meta-analysis by Roerecke and Rehm (Roerecke M., Rehm J. The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis. Addiction2012;107:1246–60). Some of his criticisms (Addiction 2012;107:1261-62) are addressed below:
“too much heterogeneity to be certain about any association”
A substantial part of the unexplained heterogeneity might have been caused by irregular heavy drinking occasions, which Roerecke & Rehm were unable to investigate in this meta-analysis, however, in a previous meta-analysis Roerecke & Rehm found an RR of 1.45 (95% CI: 1.24–1.70) for participants with binge drinking versus no binge drinking. (Roerecke M., Rehm J. Irregular heavy drinking occasions and risk of ischemic heart disease; a systematic review and meta-analysis. Am J Epidemiol. 2010;171:633–44). In studies reporting average alcohol intake without taking binge drinking into account the cardio-protective effect of regular, moderate alcohol consumption might have been underestimated.
“The best evidence they suggest for this comes from the literature on controlled laboratory studies”
The moderate intake of alcoholic beverages leads to increases in HDL-cholesterol, apolipoprotein A1, and adiponectin and decreases in fibrinogen, all factors associated with a lower risk of ischemic heart disease. (Brien SE et al. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ 2011;342:d636). The findings described in this paper strengthen the case for a causal link between alcohol intake and a reduced risk of coronary heart disease, suggesting that the lower risk of heart disease observed among moderate drinkers is caused by the alcoholic beverage itself, and not by other associated lifestyle factors. Actually, one of the problems which may beset epidemiological studies, is the difficulty of accurately measuring the dietary intakes of participants. Biomarkers of diet promise to provide a more accurate measure of dietary intake and a more objective one in that they are not reliant on the subject’s memory (Wild CP et al. A critical evaluation of the application of biomarkers in epidemiological studies on diet and health. Br J Nutr 2001;86 Suppl 1:S37-53).
“very few controlled for potential life-style confounding factors (e.g. not smoking) that might be correlated with both moderate drinking and health”
Tim Stockwell’s statement makes you wonder whether he has actually read the paper, he comments. Of the 44 studies selected for the meta-analysis by Roerecke & Rehm, 30 studies were controlled for smoking. Moreover, 23 of these 30 studies were controlled for other confounding factors such as exercise, coffee, intake of fruit and vegetables, marital status and education.
“virtually none control for heavy episodic drinking”
Tim Stockwell uses ref. 4 for his statement of virtually no control for heavy episodic drinking. That makes you wonder whether he has read and understood the conclusions of ref. 4:
· Ref. 4 is from Am J Epidemiol. vol. 171:633-44; not volume 173:245-8 as quoted by Stockwell.
· After a strict selection procedure the authors of ref. 4 (Roerecke & Rehm) found – not virtually none – but 14 studies containing 4,718 ischemic heart disease events.
“Heavy irregular drinking occasions (>60 g of pure alcohol per occasion) were significantly associated with incidence of IHD morbidity and mortality compared with regular moderate drinking (pooled relative risk = 1.45; 95% CI: 1.24, 1.70).”
“It seems that any cardioprotective effect of moderate alcohol consumption is negated by irregular heavy drinking occasions. In turn, the cardioprotective effect of regular, moderate alcohol consumption discussed in the many studies reporting average alcohol intake without taking into account irregular heavy drinking occasions might have been underestimated. The magnitude of the underestimation depends on the prevalence of irregular heavy drinking occasions in the respective population.”
In other words a complete control of all studies for heavy episodic drinking might have increased the protective effect of regular, moderate drinking in study populations. However, there are inconsistencies in the definition of “binge drinking.” The rapid consumption of more than 5 drinks on an empty stomach surely has different effects than the consumption of alcohol over several hours with food, such as during a prolonged dinner. A population-based analysis from Denmark found that subjects who were overall “light-to-moderate” drinkers but reported an episode of “binge drinking” (consumption >5 drinks on an occasion) did not show differences in risk of ischaemic heart disease or total mortality than did other moderate drinkers who did not report such an episode. (Skov-Ettrup LS et al. Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study. Scandinavian Journal of Public Health 2011;39:880–7)
“many assessed drinking at baseline over a relatively short time-period”
Baseline assessment is common procedure in nutritional epidemiology and a source of information bias in many studies. “The most important problem in nutritional epidemiology has been inaccuracy of dietary assessment”. (Byers T. The role of epidemiology in developing nutritional recommendations: past, present and future. Am J Clin. Nutr. 1999;69:1304S-1308S) Alcohol intake is uniquely susceptible to misclassification and biased reporting. Information bias is certainly possible and even likely in observational studies of alcohol and health. However, any bias due to misclassification would tend toward the null value and thus weaken the negative association between moderate alcohol intake and ischemic heart disease. Information bias would, however, also cast doubt on the positive association between alcohol and cancer. (Shapiro S. Point/Counterpoint: Meta-analysis of observational studies. Am J Epidemiol. 1994;140:771-78.) Actually, if only a modest association exists, measurement error in dietary intake may conceal it. A true reduction in risk of coronary heart disease or increase in cancer risk of 10–30% might be impossible to detect. (Michels KB. Nutritional epidemiology - past, present, future. Int J Epidemiol. 2003;32:486-88).
“there is too much heterogeneity to be certain about any association, let alone causality”
Alcohol is one of the most investigated dietary risk factors for IHD. Using the Bradford Hill guidelines to derive a causation score based on 4 criteria (strength, consistence, temporality and coherence) the evidence for a causal link between moderate alcohol consumption and coronary heart disease was found to be moderate (3 criteria of 4 satisfied) on a par with the association for intake of fish, marine omega-3 fatty acids, folate, whole grains, dietary vitamins E and C, beta carotene, fruit and fiber. (Mente A et al. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med 2009;169:659-69.)
“The most plausible alternative explanation to there being a causal association between moderate drinking and reduced risk of some diseases is the failure to control for confounding lifestyle risk factors”
Individuals who try to eat a healthy diet are likely to lead a healthy lifestyle in general. It is probably not possible to measure all important markers of a healthy lifestyle sufficiently to eliminate confounding. The inability to distinguish the effect of diet from that of other lifestyle factors may pose a threat to the validity of diet—disease associations observed in epidemiologic studies. (Michels KB. Nutritional epidemiology - past, present, future. Int J Epidemiol 2003;32:486-88). The problems of confounding question the virtues of moderate alcohol consumption as well as the vices of alcohol abuse. Lifestyle confounding factors also question the virtues of fruit and vegetables and the vices of fat cream and white sugar. That said, solid evidence for the cardioprotective effect of moderate alcohol consumption has been found in large, homogeneous cohorts of e.g. British doctors and American Physicians. In addition the beneficial effects of alcohol consumption on biological markers associated with risk of coronary heart disease suggest that the lower risk of heart disease observed among moderate drinkers is caused by the alcoholic beverage itself, and not by other associated lifestyle factors. (Brien SE et al. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ 2011;342:d636)
“numerous studies reporting biologically implausible health benefits associated with moderate drinking”
Of the “numerous studies” Tim Stockwell just found 3 studies to quote: ref. 9, 10 and 11. Two of the 3 studies, ref. 9 and 11, concern offspring cognition following light alcohol consumption in pregnancy (ref. 9: Liang W et al. Does light alcohol consumption during pregnancy improve offspring’s cognitive development? Med Hypotheses 2012;78:69-70 plus ref. 11: Henderson J et al. Systematic review of effects of low - moderate prenatal alcohol exposure on pregnancy outcome. Br J Obstet Gynaecol 2007;114: 243-52). Maternal consumption of low to moderate quantities of alcohol during pregnancy is not associated with mean IQ of preschool children and executive functioning at the age of 5 years. This was the conclusion of a recent report from the NICE Institute and has been confirmed by 5 Danish studies published online ahead of print in BJOG 20 June 2012. Around this null effect some studies have found a negative effect and other studies have found a positive effect on cognition by light alcohol consumption during pregnancy. Some heterogeneity must be expected in the rough world of nutritional epidemiology – especially in a field of research where the endpoints are discrete differences in the cognitive function of small children.
Ref. nr. 10 (Rehm J et al. Alcohol as a risk factor for liver cirrhosis - a systematic review and meta-analysis. Drug Alcohol Rev 2010;29:437–45) found that light to moderate drinking up to two drinks among women and men was not associated with a significant increase in risk of liver cirrhosis morbidity. Nobody would expect moderate drinking to lower the risk of liver cirrhosis, which was a finding for men in the study, however, most of us would also find it surprising that 4 or more cups of coffee per day reduce the risk of alcoholic liver cirrhosis by 80%. (Klatsky AL. Coffee, Cirrhosis, and Transaminase Enzymes. Arch Intern Med 2006;166:1190-95) Results like these surface from time to time in the rough world of nutritional epidemiology, but it is malpractice of epidemiology to use such unexpected results to discredit evidence based on scores of large cohort studies.
“There are also numerous other claims of health benefits from moderate drinking which should be scrutinized more closely, ranging from preventing ailments from dementia to the common cold”
Indeed, inconsistent evidence from nutritional epidemiology should be scrutinized by all means.
(Nestel P. Nutritional evidence lacks consistency. Curr Opin Lipidol. 2007;18:1-2). For the past 30 or 40 years, dietary saturated fats have attained a poor reputation especially in relation to cardiovascular health. However, a recent meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD (Siri-Tarino PW et al. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 2010;91:535-46.) If you want to talk about much-maligned foods, butter is right up at the top of the list. Health authorities have been telling us for years that foods like butter, rich in saturated fat, are clogging our arteries and causing heart disease. However, a recent study from Australia found no consistent and significant association between total dairy intake and total or cause-specific mortality. And even more surprising, compared with those participants with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339_g/day) had reduced risk of death due to CVD: HR: 0.31; 95% confidence interval 0.12–0.79. (Bonthuis M et al. Dairy consumption and patterns of mortality of Australian adults. European Journal of Clinical Nutrition 2010;64:569–77). The list of inconsistencies in need of scrutinising is long.
“we need more than the present handful of high-quality studies and, ideally, randomized controlled trials if these should ever be possible”
Traditional cohort studies are expensive and take many years to perform. Randomized controlled allocation of diet is likely to be successful only for severe dietary deficiencies that can be reversed in a short period of time, or for allocation of dietary supplements. Studying the effects of dietary composition on long-term health using randomization presents a serious challenge. Ethical principles do not permit randomizing individuals to a diet that, according to scientific evidence, may have harmful effects. Participants can be randomized only to maintaining their diet or to a diet with uncertain impact on the health outcome of interest. Adhering to an altered diet over an extended time period presents an unreasonable challenge for most people, and sufficient differences in diet between intervention and control group are extremely difficult to maintain. (Michels KB. Nutritional epidemiology - past, present, future. Int J Epidemiol 2003;32:486-88).
Mendelian randomization is a recently developed methodology that combines genetic and classical epidemiological analysis to infer causality for environmental exposures, based on the principle of Mendel’s law of independent assortment. Mendelian randomization uses genetic variants as proxies for environmental exposures of interest. Associations derived from Mendelian randomization analysis are less likely to be affected by confounding and reverse causation. (Qi L. Mendelian randomization in nutritional epidemiology. Nutr Rev 2009;67:439-50). A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. In a nested case-control study based on data from the prospective Physicians’ Health Study moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele had higher HDL levels and a substantially decreased risk of myocardial infarction. Since the predominant function of alcohol dehydrogenase type 3 is to metabolize alcohol, this finding is consistent with the hypothesis that a slower rate of clearance of alcohol enhances the beneficial effect of moderate alcohol consumption on the risk of cardiovascular disease. (Hines LM et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549-55).
“should we be just reporting significant and large heterogeneity in study results, or perhaps seek to conduct meta-analysis with increasingly strict quality criteria”
This latter approach was used in a much discussed meta-analysis by Fillmore et al. (Fillmore KM et al. Moderate alcohol use and reduced mortality risk: systematic error in prospective studies. Addict Res Theory 2006;14:101–32). The draconian criteria used by Fillmore et al would erode the mountain of evidence from nutritional epidemiology. The evidence for benefits of exercise would probably go down the drain together with wine and vegetables, and no smoking might be the only surviving life-style advice.
In the past decade, there has been a paradigm shift in nutritional epidemiology to examine associations between dietary patterns and health. Numerous epidemiological studies show that people following the Mediterranean style diet have lower risk of CHD (Bhupathiraju SN, Tucker KL. Coronary heart disease prevention: nutrients, foods, and dietary patterns. Clin Chim Acta 2011; 412:1493-514). Analysing data from the Greek EPIC Study Antonia Trichopoulou et al found higher adherence to a Mediterranean diet associated with a statistically significant reduction in total mortality: adjusted mortality ratio per two unit increase in score 0.86, 95% confidence interval 0.80 - 0.93. The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio. (Trichopoulou A et al. Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study. BMJ2009;338:b2337). Our ancient Greek colleague Hippocrates said it well: “Wine is a thing marvellously suited to man, in health as in sickness, if it is administered appropriately, and in just measure in accordance with the individual constitution”.