ALCOHOL AND HEALTH

Morten Grønbæk

National Institute of Public Health

Copenhagen, Denmark

Mortality ->Detrimental Effects: Cirrhosis, Cancer

Positive Effects: Cardiovascular Disease

Alcohol and Health

Mortality ->Detrimental Effects: Cirrhosis, Cancer

Positive Effects: Cardiovascular Disease

Alcohol and HealthSomatic

Mortality ->Detrimental Effects: Cirrhosis, Cancer

Positive Effects: Cardiovascular Disease

Alcohol and HealthSomatic

Epidemiological evidence

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Mor

tali

ty

Boffetta et al, Epidemiology 1990

Alcohol and mortality

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Mor

tali

ty

Boffetta et al, Epidemiology 1990

Alcohol and mortality

Alcohol and mortality

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Mor

tali

ty

Boffetta et al, Epidemiology 1990

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Rel

ativ

e m

orta

lity

All

Cancer

Coronary heart disease

Boffetta et al, Epidemiology 1990

Alcohol and cause specific mortality

0

2

4

6

8

10

Alcohol intake, drinks per week

Relative risk

< 1 1 - 7 8 - 21 22 - 35 > 35

Alcohol and alcoholic cirrhosis

Drinks per week

Relative risk

< 1 1-6 7-13 14-27 28-41 42-69 >700

2

4

6

8

10

12

14

16

18

20

Alcohol and alcoholic cirrhosisSex differences

Men

WomenP < 0.05

Becker U et al., Hepatology 1996

Alcohol intake, drinks per day

  

The Copenhagen Alcohol Cohort , N=9.000

  5-9 10-14 15-19 20-24 25-29 30-34 35+

Number of individuals 439 1134 1284 1192 846 535 722

Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35

Men, percent 49 59 72 75 83 86 89

 

Kamper-Jørgensen M et al, J Hepatol 2004

Alcohol intake, drinks per day

  

The Copenhagen Alcohol Cohort , N=9.000

  5-9 10-14 15-19 20-24 25-29 30-34 35+

Number of individuals 439 1134 1284 1192 846 535 722

Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35

Men, percent 49 59 72 75 83 86 89

 

Kamper-Jørgensen M et al, J Hepatol 2004

Alcohol intake, drinks per day

  

The Copenhagen Alcohol Cohort , N=9.000

  5-9 10-14 15-19 20-24 25-29 30-34 35+

Number of individuals 439 1134 1284 1192 846 535 722

Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35

Men, percent 49 59 72 75 83 86 89

 

SMR, cirrhosis: Men 27 Women 35

Kamper-Jørgensen M et al, J Hepatol 2004

Alc cir  

Men, amount

Kamper-Jørgensen M et al, J Hepatol 2004

The Copenhagen Alcohol Cohort

Men, duration

Kamper-Jørgensen M et al, J Hepatol 2004

The Copenhagen Alcohol Cohort

Alcohol and Breast CancerCopenhagen Centre for Prospective Population Studies

  

0

0,5

1

1,5

2

2,5

3

3,5

< 1 1-6 7-13 14-27 > 27

Total alcohol intake

Rela

tiv

e r

isk

of

brea

st c

an

cer

Petri A et al, Alc Clin Exp Res 2004

Tjønneland A et al, Cancer Causes and Control 2003; 14: 277–284

Alcohol and Breast Cancer

Diet Cancer and Health Study

0,5

0,6

0,7

0,8

0,9

1

1,1

1,2

1,3

1,4

1,5

1,6

1,7

1,8

1,9

2

0 1 2 3 4 5 6

Alcohol, drinks per day

Rel

ativ

e R

isk

Alcohol and Breast CancerPooled analysis

Ellison RC, Am J Epidemiol 2001

0,5

0,6

0,7

0,8

0,9

1

1,1

1,2

1,3

1,4

1,5

1,6

1,7

1,8

1,9

2

0 1 2 3 4 5 6

Alcohol, drinks per day

Rel

ativ

e R

isk

Alcohol and Breast CancerDose-response or threshold?

Upper digestive tract cancer

0

2

4

6

8

10

12

14

0 1-6 7-21 22-41 42-69 69+

Relative risk

Alcohol, drinks per week

Grønbæk et al, BMJ 1998

Alcohol and mortality

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Mor

tali

ty

Boffetta et al, Epidemiology 1990

Alcohol and cardiovascular disease

Clinical and experimental evidence:

- High density lipoprotein (HDL)

- Low density lipoprotein (LDL)

- Platelet aggregation

- Fibrinogen

- Fibrinolysis

- Blood pressure

Age, Sex, Genes

Drinking pattern

Factors influencing the association between alcohol and cardiovascular disease

Age, Sex, Genes

Drinking pattern

Factors influencing the association between alcohol and cardiovascular disease

0,5

0,6

0,7

0,8

0,9

1,0

1,1

1,2

1,3

1,4

1,5

0 0.1-1.4 1.5-4.9 5.0-14.9 15.0-29.9 30+

Alcohol, grams per day

Mo

rta

lity

Fuchs et al, NEJM 1995

Alcohol and mortality: AgeNurses’ Health Study

0,5

1,0

1,5

2,0

2,5

3,0

0 0.1-1.4 1.5-29.9 30+

Average alcohol intake (g/day)

Mo

rtal

ity

Fuchs et al, NEJM 1995

Alcohol and mortality: AgeNurses’ Health Study

34-39 y

40-49 y

50-59 y

60+ y

Genetics: Alcohol dehydrogenase

ADH3: Functional polymorphism causing an ~3 fold difference in activity

p(ADH31) = 0.6 (fast allele)

p(ADH32) = 0.4 (slow allele)

Hines et al.: NEJM: 2001

(fast) (slow) (fast) (slow)

ADH, alcohol and myocardial infarction

Age, Sex, Genes

Drinking pattern

Factors influencing the association between alcohol and cardiovascular disease

Drinking pattern:Meal related alcohol intakeType of alcoholBinge vs steady intake

Factors influencing the association between alcohol and cardiovascular disease

Alcohol intake consumed with meals and myocardial infarction

Mukamal et al.NEJM 2003;348:109-18

Variable 0.1-4.9 g/day 5.0-29.9 g/day ≥ 30.0 g/day P value

< 25% Relative risk

95% CI1.00

-

0.67

0.45-0.99

0.57

0.32-1.03

0.05

25-74% Relative risk

95% CI1.00

-

0.78

0.29-2.07

0.51

0.15-1.77

0.28

≥ 75%

Relative risk

95% CI

1.00

-

0.92

0.52-1.63

0.33

0.09-1.27

0.16

Different alcoholic beverages and cardiovascular disease mortality

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

Never Monthly Weekly Daily,1-2 Daily,3-5

Beverage specific alcohol consumption

Rel

ativ

e ri

sk

Wine

Beer

Spirits

Grønbæk et al., BMJ 1995

Alcohol, wine and mortalityCopenhagen Centre of Prospective Population Studies

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 1-7 8-21 22-35 >35

Alcohol Consumption, drinks/wk

Mor

talit

y

0

1-30

>30

Percent wine of alcohol intake

Grønbæk et al Ann Int Med 2000; 133(6):411-419

0,4

0,6

0,8

1

1,2

1,4

1,6

0 1-7 8-21 >21

Alcohol Consumption, drinks/wk

Rel

ativ

e M

orta

lity

fro

m C

HD

Grønbæk et al Ann Int Med; 133(6):411-419

Alcohol, wine and mortality from CHD

Non-wine drinkers

Wine drinkers

0,4

0,6

0,8

1

1,2

1,4

1,6

0 1-7 8-21 22-35 >35

Alcohol Consumption, drinks/wk

Rel

ativ

e M

orta

lity

fro

m C

ance

r

Grønbæk et al Ann Int Med; 133(6):411-419

Alcohol, wine and mortality from cancer

Type of alcohol and mortalityBritish Regional Heart Study

Beer (N=4101)

Spirits (N=1724)

Wine (N=1035)

All cause mortality Age-adj RR 1.00 0.94 (0.83-1.07) 0.58 (0.47-0.70) Adjusted RR 1.00 0.99 (0.86-1.13) 0.80 (0.65-0.98)

Cardiovascular mortality Age-adj RR 1.00 1.04 (0.86-1.25) 0.54 (0.40-0.73) Adjusted RR (+) 1.00 1.03 (0.84-1.26) 0.72 (0.52-0.98)

Wannamethee and Shaper Am J Publ Health 1999

0

5

10

15

20

0 1-7 8-21 22-35 >35

Total alcohol intake; drinks/week

Rel

ativ

e ri

sk

< 1% wine1-15% wine16-30% wine31-50% wine> 50% wine

Alcohol, wine and alcoholic cirrhosis

P < 0.05

.Becker U et al., Hepatology 2002

0

1

2

3

4

5

6

0 1-6 7-21 >21Alcohol intake, drinks per week

Rel

ativ

e ri

sk o

f up

per

dige

stiv

e tr

act c

ance

r

0

1 to 30

> 30

Type of alcohol and upper digestive tract cancer

Grønbæk et al. BMJ 1998

Wine, %

Differences in morbidity and mortality

among drinkers of beer, wine and spirits

Components? Flavonoids, polyphenols, nitrosamines

Confounders?Lifestyle factors, social class, diet

Income

0,40

0,50

0,60

0,70

0,80

0,90

1,00

1,10

Never Monthly Weekly 1-2 Drinksdaily

> 2 Drinksdaily

Wine consumption

Re

lati

ve

mo

rta

lity

ris

k

Low Medium High

Nielsen et al. J Int Med 2004;255:280-8

Wine Intake, Social Status and MortalityCopenhagen City Heart Study

Diet, Cancer, and Health Study, Denmark, 1996

Alcoholic beverage preference

Fruit Fish Vegetables Salad No fats on bread

Olive oil for cooking

Wine

1 1 1 1 1 1

Beer 0.66 0.69 0.56 0.42 0.50 0.40

Spirits 0.98 0.84 0.65 0.51 0.80 0.54

Odds ratios for having an intake above the median of different foods according to preferred alcoholic beverage

 Tjønneland et al. Am J Clin Nutr 1999

Drinking pattern:Meal related alcohol intakeType of alcoholBinge vs steady intake

Factors influencing the association between alcohol and cardiovascular disease

Drinking pattern:

Binge vs steady intake

Factors influencing the association between alcohol and cardiovascular disease

- and all-cause mortality

Drinking pattern and CVD

Frequency of drinking Alcohol intake / drinking day

Days / week <10.0 g 10.0-29.9 g 30.0 g

<1 1.00 (ref)

1-2 0.85

(0.67-1.08)

0.93

(0.78-1.10)

0.84

(0.70-1.02)

3-4 0.63

(0.33-1.19)

0.67

(0.55-0.83)

0.71

(0.54-0.93)

5-7 0.68

(0.33-1.37)

0.68

(0.57-0.82)

0.63

(0.52-0.76)

Mukamal et al., N Engl J Med 2003

Drinking pattern and CHD mortality

McElduff , BMJ 1997

Days per week

Don’t drink Rarely < 1 1 or 2 3 or 4 5 or 6 Daily

Drinks per day

Don’t drink 1.00

1 to 2 1.89 0.53 0.64 0.43 0.31 0.91

3 to 4 1.36 0.43 0.63 0.43 0.31 0.81

5 to 6 0.94 1.04 0.82 0.47 0.40 0.73

>9 1.57 1.58 0.89 0.86 1.43

Cancer, Diet and Health StudyN=57.000 1996-2001

  Alcohol intake, drinks per week

1 to 6 7 to 13 14 to 21 More than 21

Characteristics* Frequent Non-frequent

Frequent Non-frequent

Frequent Non-frequent

Frequent Non-frequent

Subjects (number) 9,305 11,298 12,090 967 5,951 171 171 117

Sex (% men) 37 33 54 57 53 61 61 72

Alcohol intake (median drinks per week)

5.2 3.0 9.4 8.7 18.3 18.1 18.1 26.4

Age (mean years) 55 56 56 56 55 57 57 57

Alcohol drinking pattern and mortality

Men Women

0

1

2

3

0 <1 1-6 7-13 14-20 >21 0 <1 1-6 7-13 14+

Drinks per week

Mo

rtal

ity

Abstainers

Binge

Steady

Tolstrup et al, Addiction 2003

More evidence ?

Alcohol – positive and negative ’effects’

More evidence ?

Intervention study?

Alcohol – positive and negative ’effects’

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Rel

ativ

e m

orta

lity

What will changes in alcohol intake mean for subsequent mortality?

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alcohol, drinks per day

Rel

ativ

e m

orta

lity

Changes in alcohol intake and mortality?

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alkohol, genstande per dag

Død

elig

hed

Changes in alcohol intake and mortality?

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

0 <1 1 2 3 4 5 6+

Alkohol, genstande per dag

Død

elig

hed

Changes in alcohol intake and mortality

  Grønbæk et al., Epidemiology 2004;15(2):222-8

Alcohol intake, first examination, drinks per week

Alcohol intake, second examination, drinks per week

Number of subjects < 1 1-6 7-13 > 13

< 1 2,269 653 131 45

1-6 1,435 2,670 829 235

7-13 263 996 1,238 718

> 13 137 343 674 2,018

Copenhagen Centre for Prospective Population Studies

N = 30,630 participants

Changes in alcohol intake and mortality

  Grønbæk et al., Epidemiology 2004;15(2):222-8

Alcohol intake, first examination, drinks per week

Alcohol intake, second examination, drinks per week

Number of subjects < 1 1-6 7-13 > 13

< 1 2,269 653 131 45

1-6 1,435 2,670 829 235

7-13 263 996 1,238 718

> 13 137 343 674 2,018

Copenhagen Centre for Prospective Population Studies

N = 30,630 participants

Changes in alcohol intake and mortality

Stable intake

0,6

0,8

1

1,2

1,4

1,6

1,8

2

<1 1-6 7-13 >13

Drinks per week

Mor

tali

ty f

rom

all

cau

ses

Grønbæk et al.,Epidemiology 2004;15(2):222-8

Changes in alcohol intake and CHD mortality

Stable intake

0,6

0,8

1

1,2

1,4

1,6

1,8

2

<1 1-6 7-13 >13

Drinks per week

Mor

tali

ty f

rom

cor

onar

y he

art

dise

ase

Grønbæk et al.,Epidemiology 2004;15(2):222-8

Changes in alcohol intake and mortality

 Grønbæk et al., Epidemiology 2004;15(2):222-8

Alcohol intake at first examination

Alcohol intake at second examination

  < 1 1-6 7-13 > 13

< 1 1.00 † 0.94 (0.78-1.14) 1.04 (0.76-1.43) 1.26 (0.75-2.11)

1-6 1.21 (1.04-1.41) 1.00 † 1.00 (0.81-1.23) 1.21 (0.88-1.67)

7-13 1.39 (1.09-1.77) 0.91 (0.75-1.11) 1.00 † 1.21 (0.99-1.49)

> 13 1.44 (1.10-1.88) 1.01 (0.82-1.25) 0.89 (0.75-1.06) 1.00 †

Changes in alcohol intake and CHD mortality

 Grønbæk et al., Epidemiology 2004;15(2):222-8

Alcohol intake at first examination

Alcohol intake at second examination

  < 1 1-6 7-13 > 13

< 1 1.00 † 0.71 (0.44-1.14) 0.92 (0.45-1.90) 0.56 (0.14-2.30)

1-6 1.40 (1.00-1.95) 1.00 † 0.79 (0.48-1.30) 0.38 (0.12-1.20)

7-13 1.46 (0.86-2.45) 0.76 (0.49-1.17) 1.00 † 1.09 (0.70-1.71)

> 13 1.42 (0.71-2.82) 1.15 (0.70-1.87) 1.05 (0.70-1.56) 1.00 †

Summary

Alcohol and morbidity/mortality

Lower risk among light drinkers of any alcohol

Possibly interaction with:Age, sex and genetics factors

Drinking pattern: Beer, wine, spiritsBinge vs steady drinking