“Should We Recommend Alcohol for its Health Benefits?” R. Curtis Ellison, MD Professor of Medicine & Public Health Section of Preventive Medicine & Epidemiology Boston University School of Medicine

YES!

NO!

IT DEPENDS!

The International Scientific Forum on Alcohol Research I serve as the Scientific Co-Director of a Forum made up of an international group of 40 scientists doing research on alcohol and health and committed to balanced and well-researched data on the subject. The Forum publishes critiques of emerging reports on alcohol & health through its Boston University web-site ( forum). forumwww.bu.edu/alcohol- forum

Members, International Scientific Forum on Alcohol Research USA Luc Djoussé, MD, DSc, Dept. of Medicine, Division of Aging, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona Lynn Gretkowski, MD, Obstetrics/Gynecology, Mountainview, CA, Stanford University, Stanford, CA, USA Dwight Heath, PhD, Dept. of Anthropology, Brown University, Providence, RI, USA Imke Janssen, PhD, Department of Preventive Medicine, Rush University Medical Centre, Chicago, IL Arthur Klatsky, MD, Dept. of Cardiology, Kaiser Permanente Medical Center, Oakland, CA Lynda Powell, MEd, PhD, Chair, Dept of Preventive Medicine, Rush University Medical School, Chicago, IL Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA Yuqing Zhang, MD, DSc, Epidemiology, Boston University School of Medicine, Boston, MA

Members, International Scientific Forum on Alcohol Research Europe Alberto Bertelli, MD, PhD, Institute of Human Anatomy, University of Milan, Italy Giorgio Calabrese, MD, Docente di Dietetica e Nutrizione, Umana Università Cattolica del S. Cuore, Piacenza, Italy Maria Isabel Covas, DPharm, PhD, Cardiovascular Risk and Nutrition Research Group, Institut Municipal d´Investigació Mèdica, Barcelona, Spain Alan Crozier, PhD, Plant Biochemistry and Human Nutrition, University of Glasgow, Scotland, UK Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy Alun Evans, MD, Centre for Public Health, The Queen's University of Belfast, Belfast, UK Oliver James, MD, Head of Medicine, University of Newcastle, UK Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany Rosa M. Lamuela-Raventos, PhD, Department of Nutrition and Food Science, University of Barcelona, Spain Dominique Lanzmann-Petithory,MD, PhD, Nutrition/Cardiology, Praticien Hospitalier Hôpital Emile Roux, Paris, France Rosa M. Lamuela-Raventos, PhD, Department of Nutrition and Food Science, University of Barcelona, Spain Fulvio Mattivi, PhD, Head of the Department Good Quality and Nutrition, Research and Innovation Centre, Foundazione Edmund Mach, in San Michele all’Adige, Italy Jean-Marc Orgogozo, MD, Professor of Neurology and Head of the Neurology Divisions, the University Hospital of Bordeaux, Pessac, France Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark Jan Snel, PhD, Social and Behavioral Sciences, University of Amsterdam, Amsterdam, Holland Jeremy P E Spencer, Reader in Biochemistry, The University of Reading, UK Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway Pierre-Louis Teissedre, PhD, Faculty of Oenology - ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France Dag S. Thelle, MD, PhD, Senior Professor of Cardiovascular Epidemiology and Prevention, University of Gothenburg, Sweden; Senior Professor of Quantitative Medicine at the University of Oslo, Norway Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy David Vauzour, PhD, Senior Research Associate, Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK

Members, International Scientific Forum on Alcohol Research Australia, New Zealand, South Africa Dee Blackhurst, PhD, Lipid Laboratory, University of Cape Town Health Sciences Faculty, Cape Town, South Africa Maritha J. Kotze, PhD, Human Genetics, Dept of Pathology, University of Stellenbosch, Tygerberg, South Africa Arduino A. Mangoni, PhD, Strategic Professor of Clinical Pharmacology and Senior Consultant in Clinical Pharmacology and Internal Medicine, Department of Clinical Pharmacology, Flinders University, Bedford Park, SA; Australia Ross McCormick PhD, MSC, MBChB, Associate Dean, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand Ian Puddey, MD, Dean, Faculty of Medicine, Dentistry & Health Sciences, University of Western Australia, Nedlands, Australia Creina Stockley, PhD, MBA, Clinical Pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa

Potential Conflict of Interest Partial expenses for operating the Forum are from unrestricted donations to Boston University from associations and companies in the beverage industry (including NY Wine & Grape Foundation, Diageo, Brown-Forman) As donors have no input into the papers reviewed by the Forum or the opinions published, the IRB at Boston University has deemed that these do not constitute a conflict of interest.

“Should We Recommend Alcohol for its Health Benefits?” Among the factors that we must consider: 1.Is excessive alcohol intake associated with adverse health effects? 2.Is light-to-moderate alcohol intake associated with beneficial health effects? Is it the cause? 3.Does the pattern of drinking affect the net health effects? (speed of intake, with food, regular vs binge) 4.Does the type of beverage affect the net health effects? 5.Is the public often faced with biased, exaggerated statements about alcohol? What are proper guidelines?

Types of Scientific Evidence Case reports Ecologic data (comparing populations without individual data) Case-control studies Prospective cohort studies (may be population-based, must deal with confounders) Experimental data Human clinical trials (for intermediary outcomes, for disease outcomes)

Potential Confounding in Observational Studies There is often clustering of healthy lifestyle factors We must deal with such potentially confounding variables: Age Sex Cigarette smoking Education, occupation, and income Diet, physical activity, level of obesity Previous alcohol use Adjust for many of these factors through stratification and multivariable analysis techniques.

Research on Alcohol and Cardiovascular Disease Prospective epidemiologic studies for many decades, even when fully controlled for known confounding, have been amazingly consistent: moderate drinkers are at lower risk of CHD than are abstainers.

Alcohol & CHD: Meta-analysis Corrao et al, 2000

Alcohol Consumption and CHD Mortality: Review & Meta-analysis. Ronksley et al. BMJ 2011 Reviewed 84 well-done prospective epidemiologic studies; > 1 million subjects. Estimated effects of alcohol intake on mortality from coronary heart disease

Effects of Alcohol on Cardiovascular Disease (Ronksley et al, 2011) ■ This meta-analysis showed ■ This meta-analysis showed risk reductions for moderate alcohol drinkers of 25% for CHD mortality 29% for incident coronary heart disease 25% for cardiovascular disease mortality 13 % for all-cause mortality.

Alcohol & Mortality, adjusting for SES and a Propensity Score (Lee et al, 2009) 12,519 subjects, Health & Retirement Study With demographic adjustments, moderate drinkers ( ≤ 1 drink/day vs non-drinkers) had a RR for mortality of With full adjustments for SES, RF, behavioral factors and a propensity score for moderate drinking, RR was 0.62 (CI ).

Net Effect of Moderate Alcohol Intake on Mortality (Konnopka et al, 2009) Considered "moderate" up to 40 grams/day (more than 3 drinks/day) for men and up to 20 g/day (about 1 1/2 drinks/day) for women; included binge drinkers. Deaths "avoided" by moderate alcohol use were about twice as high (n=29,818) as the number "caused" by moderate drinking (n=14,457)

Deaths Attributable to “Moderate” Alcohol Intake (weekly mean <40 g/d for men, < 20 g/day for women) Deaths Attributable to “Moderate” Alcohol Intake (weekly mean <40 g/d for men, < 20 g/day for women) (Rehm et al, Ann Epidem, 2007)

Deaths Attributable to “Moderate” Alcohol Intake (when “binge drinkers” excluded) Deaths Attributable to “Moderate” Alcohol Intake (when “binge drinkers” excluded) (Rehm et al, Ann Epidem, 2007)

Mechanisms of Effect of Alcohol/Polyphenols on CVD Blood lipids (esp. HDL-cholesterol) Blood lipids (esp. HDL-cholesterol) Coagulation, fibrinolysis Coagulation, fibrinolysis Arterial endothelium Arterial endothelium Genes (alcohol and/or polyphenols) Genes (alcohol and/or polyphenols) Ventricular function Ventricular function Inflammation Inflammation Glucose metabolism Glucose metabolism

Mechanisms of Effect of Alcohol on Cardiovascular Disease (Collins et al, Alcoholism: Clin Exp Res, 2009)

“Healthy Lifestyle” for Prevention of Diseases of Ageing Don’t smoke Stay lean (avoid becoming obese) Exercise regularly Eat a diet low in animal fat, with lots of fiber (fruits & vegetables) and whole grains Unless contraindicated, consume ½ - 2 drinks of an alcoholic beverage daily from Stampfer, Hu, Chiuve, et al from Stampfer, Hu, Chiuve, et al

Effects of Alcohol on Risk of MI by Other Lifestyle Factors (1. non-smoking, 2. not obese, 3. active, 4. good diet) Least healthy (0-1 factors)=▲; Moderate (2-3 factors)=□; Healthy (4 factors)=◊ (Mukamal et al, Arch Intern Med 2006;166:21

Risk of Diabetes by Alcohol & Lifestyle Factors Joosten et al, Am J Clin Nutr 2010 Healthy lifestyle factors: (1) BMI <25, (2) physically active, (3) non-smoker, (4) high adherence to Dash diet __________Hazard Ratio, adjusted______ Moderate __________Hazard Ratio, adjusted______ Moderate No. of Healthy Factors Abstainer Drinker* p-trend None or < to or *“Moderate drinker” = g/d for women, g/d for men

But what about experiments and human clinical trials on alcohol & health?

Daily-moderate versus weekend-binge alcohol in mice. Liu et al. Atherosclerosis 2011

Meta-analysis of Interventional Studies of Alcohol and Coronary Heart Disease Brien SE, Ronksley PE, Turner BJ, Mukamal KJ. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta- analysis of interventional studies. Published in BMJ 2011;342:d636

Human Interventional Studies on Mechanisms of Effects of Alcohol on CV Risk (Brien et al, 2011)

Wine Increases the Number and Functional Capacity of Circulating Endothelial Progenitor Cells by Enhancing Nitric Oxide Bioavailability A Clinical Trial of 80 Healthy Adults A Clinical Trial of 80 Healthy Adults Huang et al, Arteriosclerosis Thrombis & Vasc Biol, 2010 “The intake of red wine significantly enhanced circulating endothelial progenitor cell levels and improved their functions by modifying nitric oxide bioavailability.”

Omega-3 Fatty Acids: An Untapped Resource for Improving Health R. Curtis Ellison, MD Professor of Medicine & Public Health Director, Institute on Lifestyle & Health Boston University School of Medicine Boston, MA,

Molecular Mechanisms for Increased Fibrinolysis (Booyse et al, 2007)

Effects of Moderate Drinking on All-cause Mortality

All-Cause Mortality, by Alcohol Consumption

Alcohol and Mortality (With repeated assessments of ETOH) The Zutphen Study (Streppel et al, 2009) Men followed for up to 40 years, until death in the vast majority, with repeated assessments of alcohol intake Up to 20 g/day of alcohol (vs none) was associated with 25-30% lower rates of cardiovascular and all-cause mortality

Total Mortality, by Alcohol Consumption Di Castelnuovo et al, Arch Int Med, 2006

Effects of Alcohol on All-cause Mortality by Type of Beverage

Survival after Age 50, by Long-Term Alcohol Consumption (Streppel et al, 2009)

Alcoholic Beverages and Incidence of Dementia: 34-Year Follow-up Mehlig et al, 2008 HR95% CI Wine drinkers0.60.4, 0.8 Wine only0.30.1, 0.8 Spirits drinkers1.51.0, 2.2 Conclusion: wine and spirits displayed opposing associations with dementia.

Effects of Pattern of Drinking on Cardiovascular & All-cause Mortality

Does drinking pattern modify the effect of alcohol on risk of CHD? A meta-analysis. Bagnardi et al, 2008

Effects of Changes in Alcohol Consumption and Health Outcomes

Changes in Alcohol Intake & Subsequent Risk of Diabetes Health Professionals Study, n = 38,031 subjects Joosten et al¸ Diabetes 2011 For initial non-drinkers, a 7.5 g/d increase = 22% decrease in risk Intake 4 yrs Later_____ Intake 4 yrs Later_____ Baseline >0-4.9 g/d g/d ≥30g/d p-trend >0-4.9 g/d g/d < g/d < ≥ 30 g/d

Changes in Alcohol Intake & All-Cause Mortality Among Women with Invasive Breast Cancer Newcomb et al, J Clin Oncology, 2013 (7, 780 deaths in 23,000 women with breast cancer) Changes in All-Cause Mortality Change in alcohol HR 95% CI Never drinker Drinker No change Decreased Increased Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Effects of Moderate Drinking on The Diseases of Ageing CV Diseases (↓ heart disease, stroke, CHF, vascular dis.) Metabolic Diseases (↓ diabetes, MS, osteoporosis) Cognitive Disorders (↓ Alzheimer’s, dementia) Obesity (emerging data suggest ↓ weight gain) Cancer (Abuse ↑ UADT cancers; moderate alcohol ↓ kidney cancer & lymphoma, slight ↑ breast & colon cancer risk) cancer & lymphoma, slight ↑ breast & colon cancer risk) Total mortality (↓ among moderate drinkers)

C onclusion Data over many decades (observational studies, animal experiments, & human intervention trials) have consistently shown that Moderate drinking, especially of wine, is associated with a lower risk of CVD and most of the other diseases of ageing.

Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Cumulative Outcomes, WHI Manson et al, JAMA 2013 All cardiovascular endpoints Cardiovascular deaths All cancers All-cause mortality

The Ultimate Clinical Trial on Alcohol & Health Recruit Recruit 50,000 normal, healthy 60 year-old people who are occasional drinkers with no previous hx of misuse & not confirmed abstainers Evaluate them in a run-in period, with incentives to remain for years Provide them with a blinded beverage (either containing alcohol or no alcohol) Assure that they drink a certain amount (perhaps 12 grams/alcohol) every evening, avoiding all other alcoholic beverages (except perhaps for religious services, weddings, and funerals) Closely monitor compliance (blood tests, bottle counts, etc.) ; use intensive incentives to assure continued participation Arrange follow up for years to see which group ages better and lives longer (Unlike pharmaceutical trials, must not fund this study with grants from interested parties)

Alcohol and Cancer in Women (Allen et al, 2009)

Effects of Smoking & Alcohol on Risk of Upper Aero-digestive Cancers Szymańska et al, 2011 Effects on Risk –Smoking, not heavy drinking++ –Heavy drinking and smoking++++ –Heavy drinking, not smoking+/-

Alcohol, HRT, & Breast Cancer California Teachers, n=40,000. Horn-Ross et al, 2012

Brooks PJ, Zakhari S. Moderate alcohol consumption and breast cancer in women: From epidemiology to mechanisms and interventions. Alcohol Clin Exp Res – October 2012 : Pointed out complexity in evaluating the association of alcohol and breast cancer Pointed out complexity in evaluating the association of alcohol and breast cancer Cited importance that the pattern of drinking, short duration of follow up, under-reporting of alcohol intake, etc., could have on results. Cited importance that the pattern of drinking, short duration of follow up, under-reporting of alcohol intake, etc., could have on results.

Risk of All-Cancer Deaths Among Lifetime Abstainers and Current Drinkers National Health Interview Survey, > 300,000 subjects, 8,362 cancer deaths Breslow et al, Am J Epidemiol 2011 No. RR of Cancer Death 95% CI Lifetime Abstainer1, Light drinker1, , 0.94 Moderate drinker*1, , 1.06 Heavier drinker , 1.43 *“moderate” = >3 – 7 dr/wk women, >3-14 dr/wk men)

Environmental Effects on Cancer Risk in the UK Parkin et al, Br J Cancer, 2011 An analysis estimated the proportion of cancer risk associated with environmental factors. Smoking (attributed in 19.4% of cases) was the largest factor associated with cancer risk. largest factor associated with cancer risk. Diet and obesity were the next most common; alcohol was attributed in 4% of cases.

Research on Overall Cancer Risk (EPIC, Schutze et al, 2013) While heavy alcohol intake increases upper aero- digestive cancer, overall only While heavy alcohol intake increases upper aero- digestive cancer, overall only 3 out of 10,000 cancers in women & 3 out of 1,000 cancers in men are related to moderate alcohol consumption. The authors do not add that for moderate drinking, the net effect is a reduction in total mortality, or greater survival.

Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Bias in Reports on Alcohol & Health An analysis by the Framingham Study in 1974, after 24 years of follow up in men, found that there were “4 major risk factors:” ● High blood cholesterol ● High blood pressure ● Cigarette smoking ● Abstinence from alcohol!

CHD Mortality in the Framingham Heart Study, by Alcohol Intake (1974) (Percent deaths over 24 years in Men) Alcohol consumption, drinks/day None < Non-Smokers Heavy Smokers

Response of Officials at NIH “Refer to only 3 major risk factors, and remove all references to alcohol. remove all references to alcohol. With all the abuse in this country, we With all the abuse in this country, we must not say alcohol prevents CHD.” must not say alcohol prevents CHD.” “If you must comment on alcohol, say it has no effect.” has no effect.” Seltzer CC. “Conflicts of Interest and Political Science,” J Clin Epidem 1997

Comments from an “Alcohol Expert” October, 2013 “Deaths from alcohol dwarf any small number of people who may derive benefit from low-dose alcohol. “Among all people who start drinking, 5 – 10 times as many die from it as are benefited by it.”

Total Mortality, by Alcohol Consumption Di Castelnuovo et al, 2006

Does Heavy Drinking by Adults Respond to Higher Alcohol Prices and Taxes? A Survey and Assessment (JP Nelson, Dept of Economics, Pennsylvania State Univ, 2013) Higher alcohol prices and taxes are frequently proposed as a policy tool to deal with abusive consumption A review of 19 individual-based studies that examine price responses by heavy-drinking adults finds only 2 studies with a significant negative price response among heavy drinkers. Many studies show that moderate-drinking adults have significant and substantial price/tax elasticities Many studies show that moderate-drinking adults have significant and substantial price/tax elasticities

The Impact of a Large Reduction in Alcohol Prices in Finland on Mortality Herttua et al, Int J Epidemiol, 2010 Markedly lowering the price of alcohol in Finland increased the number of alcohol-related deaths by 14-40% = 0 to 2.9 excess deaths each month, by age group Lowering the price decreased by up to 24% the number of deaths from cardiovascular disease = 0 to 24.8 excess deaths each month, by age group For all-cause mortality, 42 to 69 fewer monthly deaths

The Moral Bases for Public Health Interventions. (Cole P, Epidemiology 1995;6:78–83) (Cole P, Epidemiology 1995;6:78–83) “Policy should be based not on paternalism (‘We professionals know what is best’) but on education and the assumption that ‘informed people make healthful choices.” Cole adds, ‘‘Health education should be education and not propaganda; it becomes the latter when only one side of an issue is presented to the public.’’

Lionel Tiger on Alcohol Guidelines “We have seen the rise of what he calls ‘concernocrats,’ people who are motivated by well-meaning concern for the welfare of others and are prepared, therefore, to exert their power over the behavior and disposition of others. ‘‘It is a very tempting thing for well-meaning people to make statements about other people’s health and welfare because the population is primed for quasi-religious advice from the druids, the priests who advise us.”

Lionel Tiger on Alcohol Guidelines “Those of us in the comment business need to be extremely careful about what we say, not because people may drink too much, or too little, but because we may nominate ourselves as ‘gurus’ of everyone’s destiny and inspect their behaviors too carefully.”

Alcohol & Health Responses of Jackrabbit Johanssen, a cross- country skier aged 101, on his advice for a long and healthy life: “Don’t smoke, Get lots of exercise, Get lots of exercise, Don’t drink too much.” Don’t drink too much.” Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Alcohol & Health Responses of Jackrabbit Johanssen, a cross- country skier aged 101, on his advice for a long and healthy life: “Don’t smoke, Get lots of exercise, Get lots of exercise, Don’t drink too much. Don’t drink too much. Then, again, don’t drink too little either” Then, again, don’t drink too little either” Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients.

Current Challenges For middle-aged and older adults who have no contraindications to alcohol we can encourage regular, moderate drinking as a component of a healthy lifestyle. Make drunkenness socially unacceptable

Effects of Physical Activity on HDL-Cholesterol (NHLBI Family Heart Study; Ellison et al, 2004)

Effects of Alcohol Intake on HDL-Cholesterol (NHLBI Family Heart Study; Ellison et al, 1998)

Alcohol Intake & CHD Mortality Among Non-Diabetics & Diabetics Physicians’ Health Study, Ajani et al, 2000 Frequency of Alcohol Intake NoneMonthlyWeeklyDaily Non-Diabetics (n=717) (n=717) Diabetics (n=133) (n=133)

Moderate Alcohol Use and Cognitive Function (A Mendelian Randomization Design Study) March 2012 Headlines Mendelian randomization is the “Gold Standard” for studying alcohol and disease Mendelian randomization is the “Gold Standard” for studying alcohol and disease Moderate alcohol use is unlikely to lower risk of dementia Moderate alcohol use is unlikely to lower risk of dementia

Moderate Alcohol Use and Cognitive Function (A Mendelian Randomization Design Study) March 2012 Comments Mendelian randomization based only on ALDH2 (but explains < 3% of alcohol intake) Mendelian randomization based only on ALDH2 (but explains < 3% of alcohol intake) Ignored patterns of drinking, environmental factors affecting alcohol use

Summary of Mechanisms of Red Wine Effects (Chiva-Blanch et al, 2013)

Alcohol and Obesity Sayon-Orea et al reviewed publications on alcohol and obesity. They concluded: “It is Sayon-Orea et al reviewed publications on alcohol and obesity. They concluded: “It is possible that heavy drinkers may increase their risk of obesity. “Light-to-moderate alcohol intake, especially wine intake, may be more likely to protect against weight gain, whereas consumption of spirits has been positively associated with weight gain.”

Alcohol & Body Mass Index (by quintiles of frequency of drinking) Breslow RA et al – Am J Epidemiol 2005

Daily-moderate versus weekend-binge alcohol & body weight in mice. Liu et al, Atherosclerosis 2011

Mechanisms of Effect of Resveratrol on Cardiovascular Disease (Collins et al, 2009)

The International Scientific Forum on Alcohol Research The Forum was established in 2010, to provide critical and balanced reviews of emerging papers related to alcohol and health, published on The Forum consists of an international group of 40 invited physicians and scientists who are specialists in their fields and volunteer their services

The Intenational Scientific Forum on Alcohol Research The Institute on Lifestyle & Health at Boston University serves as the scientific center of the Forum; the Institute is supported completely by donations Since 2010, more than 120 critiques have been published by the Forum on its web-site ( Brief summaries of each critique are distributed widely by a team in the UK headed by Helena Conibear

Early-Adult Vs. Later-Adult Alcohol Intake: Framingham Study (drinks/week) (drinks/week) Later LaterEarlyNone>0-7>7-21>21Total None ,007 > , ,685 > ,261 > Total1,5474,0501, ,303

Mechanisms of Alcohol Effect on CVD in Men (Rimm & Moats, Ann Epidemiol 2007)

Mechanisms of Alcohol Effect on CVD in Women (Rimm & Moats, Ann Epidemiol 2007)

Alcohol, Wine, and Health Recent Findings (Lee et al, 2009)

Alcohol & Cardiovascular Disease Ecologic studies, such as those describing the “French Paradox,” compare populations in the aggregate, but do not contain individual data. May generate hypotheses, not test them. For the latter, clinical trials are best; but we often have to rely on prospective epidemiologic studies that are adequately adjusted for confounders.

Quotation from Abraham Lincoln "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." Lincoln A. Talk to Washington Temperance Society of Springfield, Illinois, February 22, 1842

Type of Beverage % of Coronaries with lesions Water 100% Beer 100 Whiskey 83 White wine 67 Red wine 40 Klurfeld & Kritchevsky, 1981 Coronary Atherosclerosis, by Type of Alcohol Consumed (Rabbits)

Effect of Alcohol Intake on Stent Restenosis Niroomand et al - Heart 2004 %

In Determining Alcohol Policy, We Must Avoid Publications With Bias: An inclination, a propensity, a predisposition, (towards); prejudice Ignorance: Lack of knowledge (general or particular) Pseudoscience: Pretended or spurious science; a collection of beliefs about the world mistakenly regarded as being based on scientific method or as having the status of scientific truth Misinformation: Wrong or misleading information

Klatsky has clearly stated that advice regarding alcohol depends on the individual’s age, sex, past alcohol use experience, cardiovascular risk, and other factors. We can apply similar approaches in giving population advice, as well. He added that most people know very well what the difference is between light to moderate drinking and binge or excessive drinking. While some patients may rationalize their heavy drinking because of its purported health effects, he has yet to find someone who had developed alcohol abuse because of messages about the health effects of moderate drinking. Medical practitioners, in his view, have a ‘‘solemn duty’’ to tell the truth about alcohol consumption, as they understand it, to all of their patients. Sin Taxes: Do Heterogenous Responses Undercut Their Value? Ayyagari et al, National Burerau of Econommic Research, 2009 “Only a subgroup responds significantly to price. Importantly, the unresponsive group drinks more heavily, suggesting that a higher price could fail to curb drinking by those most likely to cause negative externalities. “In contrast, those least likely to impose costs on others are more responsive, thus suffering greater deadweight loss yet with less prevention of negative externalities.”