““Should We Recommend Alcohol for its Should We Recommend Alcohol for its Health Benefits?”Health Benefits?”

R. Curtis Ellison, MDR. Curtis Ellison, MD

Professor of Medicine & Public HealthProfessor of Medicine & Public Health

Section of Preventive Medicine & EpidemiologySection of Preventive Medicine & Epidemiology

Boston University School of MedicineBoston University School of Medicine

YES!YES!

NO!NO!

IT DEPENDS!IT DEPENDS!

The International Scientific Forum The International Scientific Forum on Alcohol Researchon Alcohol Research

I serve as the Scientific Co-Director of a Forum I serve as the Scientific Co-Director of a Forum made up of an international group of 40 made up of an international group of 40 scientists doing research on alcohol and health scientists doing research on alcohol and health and committed to balanced and well-researched and committed to balanced and well-researched data on the subject. data on the subject.

The Forum publishes critiques of emerging reports The Forum publishes critiques of emerging reports on alcohol & health through its Boston on alcohol & health through its Boston University web-site (University web-site (www.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 ResearchEurope

Alberto Bertelli, MD, PhD, Institute of Human Anatomy, University of Milan, ItalyGiorgio Calabrese, MD, Docente di Dietetica e Nutrizione, Umana Università Cattolica del S. Cuore, Piacenza, ItalyMaria 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, UKGiovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo

NEUROMED, Pozzilli, ItalyAlun Evans, MD, Centre for Public Health, The Queen's University of Belfast, Belfast, UKOliver James, MD, Head of Medicine, University of Newcastle, UKUlrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, GermanyRosa 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, SpainFulvio Mattivi, PhD, Head of the Department Good Quality and Nutrition, Research and Innovation Centre, Foundazione

Edmund Mach, in San Michele all’Adige, ItalyJean-Marc Orgogozo, MD, Professor of Neurology and Head of the Neurology Divisions, the University Hospital of Bordeaux, Pessac,

FranceErik 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, UKArne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, NorwayPierre-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, NorwayFulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, ItalyDavid 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 InterestPotential Conflict of Interest

Partial expenses for operating the Forum are from Partial expenses for operating the Forum are from unrestricted donations to Boston University from unrestricted donations to Boston University from associations and companies in the beverage industry associations and companies in the beverage industry (including NY Wine & Grape Foundation, Diageo, (including NY Wine & Grape Foundation, Diageo, Brown-Forman)Brown-Forman)

As donors have no input into the papers reviewed by the As donors have no input into the papers reviewed by the Forum or the opinions published, the IRB at Boston Forum or the opinions published, the IRB at Boston University has deemed that these do not constitute a University has deemed that these do not constitute a conflict of interest.conflict of interest.

““Should We Recommend Alcohol for its Health Benefits?”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 Types of Scientific Evidence

Case reportsCase reports

Ecologic data Ecologic data (comparing populations without (comparing populations without individual data)individual data)

Case-control studiesCase-control studies

Prospective cohort studies Prospective cohort studies (may be (may be population-based, must deal with confounders)population-based, must deal with confounders)

Experimental dataExperimental data

Human clinical trials Human clinical trials (for intermediary outcomes, (for intermediary outcomes,

for disease outcomes)for disease outcomes)

Potential Confounding in Observational Potential Confounding in Observational StudiesStudies

There is often clustering of healthy lifestyle factors

We must deal with such potentially confounding variables: AgeSexCigarette smokingEducation, occupation, and incomeDiet, physical activity, level of obesityPrevious alcohol use

 

Adjust for many of these factors through stratification and multivariable analysis techniques. 

Research on Alcohol and Research on Alcohol and Cardiovascular DiseaseCardiovascular Disease

Prospective epidemiologic studies for Prospective epidemiologic studies for many decades, even when fully many decades, even when fully controlled for known confounding, controlled for known confounding, have been amazingly consistent:have been amazingly consistent:

moderate drinkers are at lower moderate drinkers are at lower risk of CHDrisk of CHD than are abstainers. than are abstainers.

Alcohol & CHD: Meta-analysisCorrao et al, 2000

Alcohol Consumption and CHD Mortality: Alcohol Consumption and CHD Mortality: Review & Meta-analysis. Review & Meta-analysis. Ronksley et al. BMJ 2011Ronksley et al. BMJ 2011

Reviewed 84 well-done prospective Reviewed 84 well-done prospective epidemiologic studies; > 1 million subjects. epidemiologic studies; > 1 million subjects.

Estimated effects of alcohol intake on Estimated effects of alcohol intake on mortality from coronary heart diseasemortality from coronary heart disease

Effects of Alcohol on Cardiovascular DiseaseEffects of Alcohol on Cardiovascular Disease(Ronksley et al, 2011)(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 Alcohol & Mortality, adjusting for SES and a Propensity Score SES and a Propensity Score (Lee et al, 2009)(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 0.50.

With full adjustments for SES, RF, behavioral factors and a propensity score for moderate drinking, RR was 0.62 (CI 0.48-0.80).

Net Effect of Moderate Alcohol Net Effect of Moderate Alcohol Intake on MortalityIntake on Mortality

((Konnopka et al, 2009)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 Deaths Attributable to “Moderate” Alcohol Intake (weekly mean <40 g/d for men, < 20 g/day for women)(weekly mean <40 g/d for men, < 20 g/day for women)

(Rehm et al, Ann Epidem, 2007)

Deaths Attributable to “Moderate” Alcohol Intake Deaths Attributable to “Moderate” Alcohol Intake (when “binge drinkers” excluded)(when “binge drinkers” excluded)

(Rehm et al, Ann Epidem, 2007)

Mechanisms of Effect of Mechanisms of Effect of Alcohol/Polyphenols on CVDAlcohol/Polyphenols on CVD

Blood lipids (esp. HDL-cholesterol)Blood lipids (esp. HDL-cholesterol)

Coagulation, fibrinolysisCoagulation, fibrinolysis

Arterial endotheliumArterial endothelium

Genes (alcohol and/or polyphenols)Genes (alcohol and/or polyphenols)

Ventricular function Ventricular function

InflammationInflammation

Glucose metabolismGlucose metabolism

Mechanisms of Effect of Alcohol on Mechanisms of Effect of Alcohol on Cardiovascular Disease Cardiovascular Disease

((Collins et alCollins et al, Alcoholism: Clin Exp Res, , Alcoholism: Clin Exp Res, 2009)2009)

““Healthy Lifestyle” for PreventionHealthy Lifestyle” for Preventionof Diseases of Ageingof Diseases of Ageing

Don’t smokeDon’t smoke

Stay lean (avoid becoming obese)Stay lean (avoid becoming obese)

Exercise regularly Exercise regularly

Eat a diet low in animal fat, with lots of Eat a diet low in animal fat, with lots of fiber (fruits & vegetables) and whole grainsfiber (fruits & vegetables) and whole grains

Unless contraindicated, consume ½ - 2 Unless contraindicated, consume ½ - 2 drinks of an alcoholic beverage dailydrinks of an alcoholic beverage daily

from Stampfer, Hu, Chiuve, et alfrom 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 FactorsRisk of Diabetes by Alcohol & Lifestyle FactorsJoosten et al, Am J Clin Nutr 2010Joosten et al, Am J Clin Nutr 2010

Healthy lifestyle factorsHealthy lifestyle factors: (1) BMI <25, (2) physically active, (3) : (1) BMI <25, (2) physically active, (3) non-smoker, (4) high adherence to Dash dietnon-smoker, (4) high adherence to Dash diet

____________________Hazard Ratio, adjustedHazard Ratio, adjusted____________ Moderate Moderate

No. of Healthy FactorsNo. of Healthy Factors AbstainerAbstainer DrinkerDrinker* * p-trend p-trend

None or 1None or 1 3.90 1.983.90 1.98 < 0.001 < 0.001

2 to 32 to 3 2.68 2.68 1.21 1.21 0.002 0.002

3 or 43 or 4 1.00 1.00 0.56 0.56 0.02 0.02

*“Moderate drinker” = 5 - 14.9 g/d for women, 5 - 29.9 g/d for men*“Moderate drinker” = 5 - 14.9 g/d for women, 5 - 29.9 g/d for men

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

health?health?

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

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

Meta-analysis of Interventional Studies of Meta-analysis of Interventional Studies of Alcohol and Coronary Heart DiseaseAlcohol and Coronary Heart Disease

Brien SE, Ronksley PE, Turner BJ, Mukamal KJ. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ.

Effect of alcohol consumption on biological Effect of alcohol consumption on biological markers associated with risk of coronary markers associated with risk of coronary heart disease: systematic review and meta-heart disease: systematic review and meta-analysis of interventional studies. analysis of interventional studies.

Published in BMJ 2011;342:d636Published in BMJ 2011;342:d636

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

Wine Increases the Number and Functional Capacity Wine Increases the Number and Functional Capacity of Circulating Endothelial Progenitor Cells by of Circulating Endothelial Progenitor Cells by

Enhancing Nitric Oxide BioavailabilityEnhancing Nitric Oxide Bioavailability

A Clinical Trial of 80 Healthy AdultsA Clinical Trial of 80 Healthy Adults

Huang et al, Arteriosclerosis Thrombis & Vasc Biol, 2010Huang 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: Omega-3 Fatty Acids: An Untapped Resource An Untapped Resource

for Improving Healthfor Improving Health

R. Curtis Ellison, MDR. Curtis Ellison, MDProfessor of Medicine & Public HealthProfessor of Medicine & Public Health

Director, Institute on Lifestyle & HealthDirector, Institute on Lifestyle & Health

Boston University School of MedicineBoston University School of Medicine

Boston, MA, Boston, MA,

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

Effects of Moderate Drinking Effects of Moderate Drinking

on All-cause Mortalityon All-cause Mortality

All-Cause Mortality, by Alcohol All-Cause Mortality, by Alcohol ConsumptionConsumption

Alcohol and MortalityAlcohol and Mortality(With repeated assessments of ETOH)(With repeated assessments of ETOH)

The Zutphen Study (Streppel et al , 2009)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 Up to 20 g/day of alcohol (vs none) was associated with 25-30% lower rates of associated with 25-30% lower rates of cardiovascular and all-cause mortality cardiovascular and all-cause mortality

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

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

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

Alcoholic Beverages and Incidence of Dementia: 34-Year Follow-up Mehlig et al, 2008

HR 95% CI

Wine drinkers 0.6 0.4, 0.8

Wine only 0.3 0.1, 0.8

Spirits drinkers 1.5 1.0, 2.2

Conclusion: wine and spirits displayed opposing associations with dementia.

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

MortalityMortality

Does drinking pattern modify the effect of Does drinking pattern modify the effect of alcohol on risk of CHD? A meta-analysis.alcohol on risk of CHD? A meta-analysis.

Bagnardi et al, 2008Bagnardi et al, 2008

Effects of Changes in Alcohol Effects of Changes in Alcohol Consumption and Health Consumption and Health

OutcomesOutcomes

Changes in Alcohol Intake & Subsequent Risk of Changes in Alcohol Intake & Subsequent Risk of DiabetesDiabetes

Health Professionals Study, n = 38,031 subjects Health Professionals Study, n = 38,031 subjects

Joosten et al¸ Diabetes 2011Joosten et al¸ Diabetes 2011

For initial non-drinkers, a 7.5 g/d increase = 22% decrease in riskFor initial non-drinkers, a 7.5 g/d increase = 22% decrease in risk

Intake 4 yrs Later_____ Intake 4 yrs Later_____

BaselineBaseline >0-4.9 g/d>0-4.9 g/d 5-29.9g/d5-29.9g/d ≥≥30g/d30g/d p-trendp-trend

>0-4.9 g/d >0-4.9 g/d 1.00 0.75 1.00 0.75 0.35 < 0.001 0.35 < 0.001

5-29.9 g/d5-29.9 g/d 1.09 1.09 0.74 0.74 0.59 < 0.001 0.59 < 0.001

≥≥ 30 g/d30 g/d 0.78 0.78 0.67 0.50 0.08 0.67 0.50 0.08

Changes in Alcohol Intake & All-Cause Mortality

Among Women with Invasive Breast CancerNewcomb 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 1.0 --

Drinker

No change 0.86 0.71-1.03

Decreased 1.03 0.85-1.25

Increased 0.76 0.60-0.97

Effects of Moderate Drinking on Effects of Moderate Drinking on The Diseases of AgeingThe Diseases of Ageing

CV DiseasesCV Diseases (↓ heart disease, stroke, CHF, vascular dis.)(↓ heart disease, stroke, CHF, vascular dis.)

Metabolic DiseasesMetabolic Diseases ((↓↓ diabetes, MS, osteoporosis) diabetes, MS, osteoporosis)

Cognitive Disorders Cognitive Disorders ((↓↓ Alzheimer’s, dementia) Alzheimer’s, dementia)

Obesity Obesity (emerging data suggest (emerging data suggest ↓↓ weight gain) weight gain)

Cancer Cancer (Abuse (Abuse ↑ ↑ UADT cancers; moderate alcohol UADT cancers; moderate alcohol ↓ ↓ kidney kidney

cancer & lymphoma, slight cancer & lymphoma, slight ↑↑ breast & colon cancer risk) breast & colon cancer risk)

Total mortalityTotal mortality (↓ among moderate drinkers)(↓ among moderate drinkers)

CConclusiononclusion

Data over many decades (observational studies, Data over many decades (observational studies, animal experiments, & human intervention animal experiments, & human intervention trials) have consistently shown that trials) have consistently shown that

Moderate drinking, especially of wine, is Moderate drinking, especially of wine, is associated with a lower risk of CVD and most associated with a lower risk of CVD and most of the other diseases of ageingof the other diseases of ageing..

Cumulative Outcomes, WHICumulative Outcomes, WHIManson et al, JAMA 2013Manson et al, JAMA 2013

All cardiovascular endpoints

Cardiovascular deaths

All cancers

All-cause mortality

All cardiovascular endpointsCardiovascular deaths

All cancers

All-cause mortality

The Ultimate Clinical Trial on Alcohol & HealthThe 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 20-25 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 20-25 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 WomenAlcohol and Cancer in Women (Allen et al, 2009)(Allen et al, 2009)

Effects of Smoking & Alcohol on Effects of Smoking & Alcohol on Risk of Upper Aero-digestive CancersRisk of Upper Aero-digestive Cancers

Szymańska et al, 2011Szymańska et al, 2011

Effects on RiskEffects on Risk

– Smoking, not heavy drinkingSmoking, not heavy drinking ++++

– Heavy drinking and smokingHeavy drinking and smoking ++++++++

– Heavy drinking, not smokingHeavy drinking, not smoking +/-+/-

Alcohol, HRT, & Breast Cancer Alcohol, HRT, & Breast Cancer California Teachers, n=40,000. Horn-Ross et al, 2012California 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 Pointed out complexity in evaluating the association of alcohol and breast cancerassociation of alcohol and breast cancer

•

• Cited importance that the pattern of drinking, Cited importance that the pattern of drinking, short duration of follow up, under-reporting of short duration of follow up, under-reporting of alcohol intake, etc., could have on results.alcohol intake, etc., could have on results.

Risk of All-Cancer Deaths Among Risk of All-Cancer Deaths Among Lifetime Abstainers and Current DrinkersLifetime Abstainers and Current Drinkers

National Health Interview Survey, > 300,000 subjects, 8,362 cancer deaths National Health Interview Survey, > 300,000 subjects, 8,362 cancer deaths

Breslow et al, Am J Epidemiol 2011Breslow et al, Am J Epidemiol 2011

No. RR of Cancer DeathNo. RR of Cancer Death 95% CI 95% CI

Lifetime AbstainerLifetime Abstainer 1,9581,958 1.0 1.0 -- --

Light drinkerLight drinker 1,669 1,669 0.87 0.87 0.80, 0.94 0.80, 0.94

Moderate drinker*Moderate drinker* 1,0911,091 0.96 0.96 0.87, 1.06 0.87, 1.06

Heavier drinker Heavier drinker 622 622 1.27 1.27 1.14, 1.43 1.14, 1.43

*“moderate” = >3 – 7 dr/wk women, >3-14 dr/wk men)

Environmental Effects on Environmental Effects on Cancer Risk in the UKCancer Risk in the UK

Parkin et al, Br J Cancer, 2011 Parkin et al, Br J Cancer, 2011

An analysis estimated the proportion of cancer risk An analysis estimated the proportion of cancer risk associated with environmental factors.associated with environmental factors.

SmokingSmoking (attributed in 19.4% of cases) was the (attributed in 19.4% of cases) was the largest factor associated with cancer risk.largest factor associated with cancer risk.

DietDiet and and obesityobesity were the next most common; were the next most common; alcoholalcohol was was attributed in 4% of cases.attributed in 4% of cases.

Research on Overall Cancer RiskResearch on Overall Cancer Risk(EPIC, Schutze et al, 2013)(EPIC, Schutze et al, 2013)

While While heavyheavy alcohol intake increases upper aero- alcohol intake increases upper aero-digestive cancer, overall only 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.

Bias in Reports on Alcohol & HealthBias in Reports on Alcohol & Health

An analysis by the Framingham Study in An analysis by the Framingham Study in 1974, after 24 years of follow up in men, 1974, after 24 years of follow up in men, found that there were “4 major risk factors:” found that there were “4 major risk factors:”

● ● HHigh blood cholesteroligh blood cholesterol● ● HHigh blood pressureigh blood pressure● ● Cigarette smokingCigarette smoking● ● Abstinence from alcohol!Abstinence from alcohol!

CHD Mortality in the Framingham CHD Mortality in the Framingham Heart Study, by Alcohol Intake (1974)Heart Study, by Alcohol Intake (1974)

(Percent deaths over 24 years in Men)(Percent deaths over 24 years in Men)

Alcohol consumption, drinks/dayAlcohol consumption, drinks/day

NoneNone < 0.5< 0.5 0.5-1.00.5-1.0 1.1-2.01.1-2.0 2.1-5.92.1-5.9 6.0+6.0+

Non-SmokersNon-Smokers 16.316.3 14.814.8 14.614.6 7.87.8 5.75.7 7.47.4

Heavy SmokersHeavy Smokers 28.328.3 16.016.0 14.414.4 14.014.0 13.113.1 12.512.5

Response of Officials at NIHResponse of Officials at NIH

““Refer to only 3 major risk factors, and 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, weWith 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 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 Seltzer CC. “Conflicts of Interest and Political Science,” J Clin Epidem 19971997

Comments from an “Alcohol Expert”Comments from an “Alcohol Expert”October, 2013October, 2013

““Deaths from alcohol dwarf any small number of Deaths from alcohol dwarf any small number of people who may derive benefit from low-dose alcohol. people who may derive benefit from low-dose alcohol.

““Among all people who start drinking, 5 – 10 times as Among all people who start drinking, 5 – 10 times as many die from it as are benefited by it.”many die from it as are benefited by it.”

Total Mortality, by Alcohol ConsumptionTotal Mortality, by Alcohol ConsumptionDi Castelnuovo et al, 2006Di 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 Many studies show that moderate-drinkingmoderate-drinking adults have significant adults have significant and substantial price/tax elasticitiesand 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.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 GuidelinesLionel Tiger on Alcohol Guidelines

““We have seen the rise of what he calls ‘concernocrats,’ people We have seen the rise of what he calls ‘concernocrats,’ people who are motivated by well-meaning concern for the welfare of who are motivated by well-meaning concern for the welfare of others and are prepared, therefore, to exert their power over others and are prepared, therefore, to exert their power over the behavior and disposition of others. the behavior and disposition of others.

‘‘‘‘It is a very tempting thing for well-meaning people to make It is a very tempting thing for well-meaning people to make statements about other people’s health and welfare because the statements about other people’s health and welfare because the population is primed for quasi-religious advice from the population is primed for quasi-religious advice from the druids, the priests who advise us.”druids, the priests who advise us.”

Lionel Tiger on Alcohol GuidelinesLionel Tiger on Alcohol Guidelines

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

Alcohol & HealthAlcohol & Health

Responses of Jackrabbit Johanssen, a cross-Responses of Jackrabbit Johanssen, a cross-country skier aged 101, on his advice for a country skier aged 101, on his advice for a long and healthy life:long and healthy life:

““Don’t smoke,Don’t smoke,

Get lots of exercise, Get lots of exercise,

Don’t drink too much.”Don’t drink too much.”

Alcohol & HealthAlcohol & Health

Responses of Jackrabbit Johanssen, a cross-Responses of Jackrabbit Johanssen, a cross-country skier aged 101, on his advice for a country skier aged 101, on his advice for a long and healthy life:long and healthy life:

““Don’t smoke,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 drinkThen, again, don’t drink too little either” too little either”

Current ChallengesCurrent Challenges

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

Make drunkenness socially unacceptableMake drunkenness socially unacceptable

Effects of Physical Activity Effects of Physical Activity on HDL-Cholesterolon HDL-Cholesterol

(NHLBI Family Heart Study; Ellison et al, 2004)(NHLBI Family Heart Study; Ellison et al, 2004)

Effects of Alcohol Intake Effects of Alcohol Intake on HDL-Cholesterolon HDL-Cholesterol

(NHLBI Family Heart Study; Ellison et al, 1998)(NHLBI Family Heart Study; Ellison et al, 1998)

Alcohol Intake & CHD Mortality Alcohol Intake & CHD Mortality Among Non-Diabetics & DiabeticsAmong Non-Diabetics & Diabetics

Physicians’ Health Study, Ajani et al, 2000Physicians’ Health Study, Ajani et al, 2000

Frequency of Alcohol IntakeFrequency of Alcohol Intake

NoneNone MonthlyMonthly WeeklyWeekly DailyDaily

Non-DiabeticsNon-Diabetics (n=717)(n=717)

1.01.0 1.021.02 0.820.82 0.610.61

DiabeticsDiabetics (n=133)(n=133)

1.01.0 1.111.11 0.670.67 0.420.42

Moderate Alcohol Use and Cognitive Function (A Mendelian Randomization Design Study)

March 2012

HeadlinesHeadlines

• Mendelian randomization is the “Gold Standard” for studying Mendelian randomization is the “Gold Standard” for studying alcohol and diseasealcohol and disease

• Moderate alcohol use is Moderate alcohol use is unlikely to lower risk of dementiaunlikely to lower risk of dementia

•

Moderate Alcohol Use and Cognitive Function (A Mendelian Randomization Design Study)

March 2012

CommentsComments

• Mendelian randomization based only on Mendelian randomization based only on ALDH2 (but explains < 3% of alcohol intake)ALDH2 (but explains < 3% of alcohol intake)

• Ignored patterns of drinking, environmental factors affecting alcohol use

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

www.bu.edu/alcohol-forum

Alcohol and Obesity Alcohol and Obesity 2011-20132011-2013

Sayon-Orea et al reviewed publications on alcohol and Sayon-Orea et al reviewed publications on alcohol and obesity. They concluded: “It is 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 IndexAlcohol & Body Mass Index (by quintiles of frequency of drinking)(by quintiles of frequency of drinking)

Breslow RA et al – Am J EpidemiolBreslow RA et al – Am J Epidemiol 20052005

Daily-moderate versus weekend-binge alcohol Daily-moderate versus weekend-binge alcohol & body weight in mice. & body weight in mice.

Liu et al, Atherosclerosis 2011 Liu et al, Atherosclerosis 2011

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

The International Scientific Forum The International Scientific Forum on Alcohol Researchon Alcohol Research

The Forum was established in 2010, to provide critical and The Forum was established in 2010, to provide critical and balanced reviews of emerging papers related to alcohol balanced reviews of emerging papers related to alcohol and health, published on and health, published on www.bu.edu/alcohol-forum

The Forum consists of an international group of 40 invited The Forum consists of an international group of 40 invited physicians and scientists who are specialists in their fields physicians and scientists who are specialists in their fields and volunteer their servicesand volunteer their services

The Intenational Scientific Forum on The Intenational Scientific Forum on Alcohol ResearchAlcohol Research

The Institute on Lifestyle & Health at Boston University The Institute on Lifestyle & Health at Boston University serves as the scientific center of the Forum; the Institute is serves as the scientific center of the Forum; the Institute is supported completely by donationssupported completely by donations

Since 2010, more than 120 critiques have been published by Since 2010, more than 120 critiques have been published by the Forum on its web-site (the Forum on its web-site (www.bu.edu/alcohol-forum).).

Brief summaries of each critique are distributed widely by a Brief summaries of each critique are distributed widely by a team in the UK headed by Helena Conibearteam in the UK headed by Helena Conibear

Early-Adult Vs. Later-Adult Alcohol Intake: Early-Adult Vs. Later-Adult Alcohol Intake: Framingham StudyFramingham Study

(drinks/week) (drinks/week)

LaterLater

EarlyEarly

NoneNone >0-7>0-7 >7-21>7-21 >21>21 TotalTotal

NoneNone 531531 464464 1111 11 1,0071,007

>0-7>0-7 931931 3,1573,157 559559 3838 4,6854,685

>7-21>7-21 6060 401401 693693 107107 1,2611,261

>21>21 2525 2828 123123 174174 350350

TotalTotal 1,5471,547 4,0504,050 1,3861,386 320320 7,3037,303

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

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

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

Alcohol & Cardiovascular DiseaseAlcohol & Cardiovascular Disease

Ecologic studies, such as those describing the Ecologic studies, such as those describing the “French Paradox,” compare populations in the “French Paradox,” compare populations in the aggregate, but do not contain individual data. aggregate, but do not contain individual data. May May generate hypotheses, not test them.generate hypotheses, not test them.

For the latter, For the latter, clinical trialsclinical trials are best; but we often are best; but we often have to rely on have to rely on prospective epidemiologic prospective epidemiologic studiesstudies that are adequately adjusted for that are adequately adjusted for confounders.confounders.

Quotation from Quotation from Abraham LincolnAbraham Lincoln

"It has long been recognized that the "It has long been recognized that the problems with alcohol relate not to problems with alcohol relate not to the use of a bad thing, but to the the use of a bad thing, but to the abuse of a good thing."abuse of a good thing."

Lincoln A. Talk to Washington Temperance Lincoln A. Talk to Washington Temperance Society of Springfield, Illinois, February 22, 1842 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 Effect of Alcohol Intake on Stent RestenosisStent Restenosis

Niroomand et al - Heart 2004Niroomand et al - Heart 2004

0

10

20

30

40

50

Restenosis Repeat Angioplasty

<50g/wk>50g/wk

%

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

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.”