After exclusions we reviewed 42 experimental studies of alcohol, providing 67 separate data records. For the main analysis we excluded six data records from studies in which participants who usually consumed alcohol were restricted from any intake for several weeks, because the baseline measure of alcohol is less precise than in studies in which standard amounts of alcohol were given.
High density lipoprotein cholesterol
Results on change in high density lipoprotein cholesterol concentrations were available from 36 data records from 25 studies (see table A on website). After consumption of an average 40.9 g of alcohol a day for 4.1 weeks, high density lipoprotein cholesterol concentrations increased by an average of 5.1 mg/dl. In an unweighted regression model high density lipoprotein cholesterol concentrations increased by 0.122 mg/dl per gram of alcohol a day (fig ). After weighting each study as described high density lipoprotein cholesterol concentrations increased by 0.133 mg/dl per gram of alcohol consumed a day. The average individual consuming 30 g of alcohol a day would expect an increase in high density lipoprotein cholesterol concentration of 3.99 mg/dl (95% confidence interval 3.25 to 4.73) compared with an individual who abstains—an 8.3% increase from pretreatment values (fig ).
Weighted regression analysis of alcohol and high density lipoprotein cholesterol concentration from 36 data records abstracted from experimental studies of alcohol intake
Percentage change in biomarkers associated with intake of 30 g of alcohol a day
Although we observed no significant confounding or modification of the effects of alcohol on high density lipoprotein cholesterol concentration by sex, duration of study, median age, or beverage type we did find some qualitative differences. Among men (29 records) the coefficient for a 1 g increase in alcohol was stronger (b=0.134 mg/dl) than in women (three records) (b=0.095 mg/dl; interaction, P=0.93). Among five studies with average baseline high density lipoprotein cholesterol concentrations below 40 mg/dl the effect of alcohol was stronger (b=0.138) than among the 18 studies with concentrations above 48 mg/dl (b=0.110; interaction, P=0.04). Among the five studies that selected physically fit participants the effect of alcohol was weaker (b=0.108) than in the four studies of sedentary participants (b=0.190; interaction, P=0.45). The coefficients for alcohol from beer (b=0.160; 13 studies), wine (b=0.132; 11), and spirits (b=0.111; 4) were not significantly different from each other or from the coefficient among the remaining studies that provided either ethanol or non-specific alcohol containing beverages (b=0.128; 8).
Apolipoprotein A I
An average of 37.6 g of alcohol a day was consumed for 3.9 weeks resulting in an increase in apolipoprotein A I concentrations of 11.83 mg/dl. After weighting each of the 24 data records we found a 0.294 mg/dl increase in apolipoprotein A I concentrations per gram of alcohol consumed a day (P<0.001). The average individual consuming 30 g of alcohol a day showed an 8.82 mg/dl (7.79 to 9.86) increase in apolipoprotein A I concentrations (6.5% increase over baseline; fig ).
From 35 data records we found that triglyceride concentrations increased by 0.19 mg/dl per gram of alcohol consumed a day (P=0.001) and 5.69 mg/dl (2.49 to 8.89) per 30 g consumed a day (5.9% increase over baseline; fig ).
The coefficient for alcohol was stronger among the 26 studies in men (b=0.22; P=0.003) than among the three studies in women (b=-0.09; P=0.41), but the small number of studies conducted only among women limits our power to observe differences. The coefficient for 11 studies with only beer (b=0.27) was slightly stronger than the coefficient for 11 studies with only wine (b=0.20) and for six studies with only spirits (b=0.17), but the differences were not significant.
Alcohol intake has been associated with a favourable thrombolytic profile in many cross sectional studies12,13,22–25
and in several experimental studies (see table B on website). Many studies have used in vitro or ex vivo measures of platelet aggregation, but assay methods vary greatly and few such markers have been linked with risk of coronary heart disease. Only a few studies have assessed concentrations of fibrinogen, plasminogen, tissue type plasminogen activator, plasminogen activator inhibitor-1, factor VII, and von Willebrand factor (see table B on website)—factors that have been associated with risk of coronary heart disease.26–28
Weighted regression analyses for each of these haemostatic factors was suggestive of a more thrombolytic profile, but none was significantly affected by moderate alcohol intake (fig ). From the weighted regression equations an increment of 30 g of alcohol a day was associated with a 7.5 mg/dl (−17.7 to 32.7) decrease in fibrinogen concentration, a 1.25 ng/ml (−0.31 to 2.81) increase in tissue type plasminogen activator antigen concentration, and a 1.47% (−1.18 to 4.42) increase in plasminogen concentration. Lp(a) lipoprotein—a lipoprotein particle that may affect the fibrinolytic cascade—was only assessed in four studies (five data records) and was modestly, and non-significantly, decreased by 0.70 mg/dl (−3.38 to 1.99) for each 30 g increment of alcohol a day. We did not include activity of tissue type plasminogen activator owing to substantial differences in assay methods and heterogeneity of results. Furthermore, it is not clear that acute changes in tissue type plasminogen activator caused by alcohol intake should be used to determine subsequent risk of coronary heart disease because concentrations may also be influenced by extent of existing coronary disease.27
Sufficient data were not available to calculate a weighted average for von Willebrand factor or factor VII, but alcohol tended to lower the concentrations of both.w37 w50
The effect of alcohol on many other biochemical variables (for example, insulin, glucose, carotenoids, folate, lipid peroxidation, low density lipoprotein cholesterol, apolipoprotein B) has been assessed, but we excluded from this analysis those risk factors that had not been consistently found to be altered by alcohol, for which fewer than four data records were available, or that had not been consistently linked to risk of coronary heart disease.
Quantitative prediction of reduction in coronary heart disease risk among moderate drinkers
Using the effect sizes estimated for a 30 g increase in alcohol intake a day and results from studies of biological markers and risk of coronary heart disease we computed the expected change in risk associated with consuming 30 g of alcohol a day compared with abstaining. No single epidemiological study has simultaneously calculated the risk of coronary heart disease associated with all biological markers. Therefore, we used several similar studies,26,29–31
which provided multivariate relative risk estimates for differences in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, triglycerides, and fibrinogen (table).
The average increase in high density lipoprotein concentrations of 3.99 mg/dl for an intake of 30 g of alcohol a day would be associated with a risk reduction of 13.5% (4.3% to 24.2%) among men in the physicians' health study29
; a similar reduction of 13.3% (10.6% to 15.9%) would be expected on the basis of results from the lipids research clinics study.32
If we adjust the effect estimate for intraindividual variability in high density lipoprotein cholesterol concentrations20
we estimate a 16.8% reduction in risk of coronary heart disease directly attributable to increased high density lipoprotein cholesterol concentration from consuming 30 g of alcohol a day. Because the effect of alcohol on high density lipoprotein cholesterol concentration was stronger in those with lower baseline concentrations the predicted 5.09 mg/dl increase for those with an average concentration of 35 mg/dl would lower the risk of coronary heart disease by 20.9% after adjustment for intraindividual variability. Because concentrations of high density lipoprotein cholesterol and apolipoprotein A I are highly correlated, and the predicted reduction in risk was comparable for intakes of 30 g of alcohol a day, we assumed that the increase in concentrations of both markers were not independent and reflect the same biological phenomenon.
The small but consistent positive association between alcohol and triglyceride concentration may attenuate the benefits of alcohol. From the physicians' health study we project that the 5.69 mg/dl increase in triglyceride concentration from consuming 30 g of alcohol a day may increase the risk of coronary heart disease by 1.9% (0.5% to 3.3%); 4.6% after adjustment for intraindividual variability in triglyceride concentration.
Estimates of benefits of alcohol owing to haemostatic factors is less robust because fewer experimental studies have assessed these markers and, apart from fibrinogen, the results that link these biomarkers with risk of coronary heart disease are inconsistent. We predict a 7.5 mg/100 ml decrease in fibrinogen concentration associated with an intake of 30 g of alcohol a day, but this decrease was not significant. Such a decrease, however, would lower the risk of coronary heart disease by 4.3% (2.0% to 6.5%) based on the Northwick Park study.27
Adjusting the estimate for intraindividual variability, the predicted risk reduction for an intake of 30 g of alcohol a day would be 12.5%.
If high density lipoprotein cholesterol, fibrinogen, and triglycerides act independently to raise or lower the risk of coronary heart disease the overall benefit projected from consuming 30 g of alcohol a day would be 24.7% after adjustment for measurement error (table). This probably underestimates the true risk reduction associated with consuming 30 g of alcohol a day because it ignores the changes in concentrations of plasminogen, Lp(a) lipoprotein, insulin, platelet aggregation, factor VII, and von Willebrand factor.