The literature search identified 4690 articles pertaining to the relevant exposure, outcomes, and study designs (fig 1). Two additional articles were added from the bibliographic search. No additional articles were suggested by the content expert (KJM). After the final review, 63 articles were deemed eligible for analysis. Selected studies examined the effect of alcohol consumption on: lipid biomarkers (47 studies), inflammatory markers (13), haemostatic factors (14), endothelial factors (3), and adipocyte hormones (8). Many of the studies examined several of the biomarkers (fig 1).
Fig 1Flow of studies through review
Table 1 outlines the characteristics of the 63 included studies, totalling 1686 participants (1049 men and 625 women; one study of 12 participants did not indicate sex).20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82
Thirty six of the 63 (57%) studies included only men, eight (12.7%) included only women, and 19 (30%) included both. Thirty six studies used a crossover design and 24 used a before and after design, whereas three were parallel arm controlled trials. The control beverage was generally water, fruit juice, or a de-alcoholised drink (wine or beer), and most studies included a washout period of no alcohol use that was of similar duration to the period of alcohol intervention. Several studies included participants whose clinical characteristics may have influenced some of the biomarkers (for example, patients with diabetes, smokers, or those who were overweight or obese). Twenty eight (44%) studies controlled for an increase in caloric intake from alcohol consumption with isocaloric or controlled diets, whereas others maintained their usual diet. Six studies included people who were overweight or obese and three studies specifically examined inactive people compared with regular runners.
Table 1 Characteristics of included studies examining the impact of alcohol interventions (1 week or greater in duration) on fasting plasma concentrations of biomarkers associated with cardiovascular disease
Of the 63 studies, 44 reported adequate data to permit pooled analyses (see web extra figure). Most commonly, studies could not be included because they did not report data in a format that permitted pooling (for example, graphically or as percentage change), or did not report error calculations. The subsets of identified studies with adequate data dealt with levels of high density lipoprotein cholesterol (33 of 44), total cholesterol (26 of 32), triglycerides (31 of 39), low density lipoprotein cholesterol (24 of 28), apolipoprotein A1 (16 of 22), Lp(a) lipoprotein (3 of 5), C reactive protein (5 of 8), interleukin 6 (2 of 4), tumour necrosis factor α (3 of 7), plasminogen activator inhibitor 1 (3 of 3), tissue plasminogen activator (3 of 4), fibrinogen (7 of 8), and adiponectin (4 of 7; see web extra figure). See web extra appendix 2 for details about exclusion of studies from meta-analysis.
The pooled analysis of the effect of alcohol consumption on mean high density lipoprotein cholesterol showed a consistent increase in these levels but with significant heterogeneity among studies (fig 2 and table 2; P=0.005). Pooling of studies stratified by dose may partially explain this heterogeneity. A significant dose-response was observed between alcohol consumption and high density lipoprotein cholesterol levels (fig 2): 12.5-29.9 g/day (1-2 drinks, n=7), mean difference of 0.072 mmol/L (95% confidence interval: 0.024 to 0.119); 30-60 g/day (2-4 drinks, n=24), mean difference of 0.103 mmol/L (0.065 to 0.141); and >60 g/day (≥5 drinks, n=2), mean difference of 0.141 mmol/L (0.042 to 0.240; P for trend 0.013). Similar to the effect with high density lipoprotein cholesterol, apolipoprotein A1 also significantly increased in a random effects model pooling 16 studies (table 2).
Fig 2Forest plot of meta-analysis (random effects) of effect of alcohol consumption on levels of high and low density lipoprotein cholesterol
Table 2 Summary of pooled mean difference in biomarker level after alcohol use
In contrast, alcohol consumption did not significantly change levels of total cholesterol, low density lipoprotein cholesterol, triglycerides, or Lp(a) lipoprotein (table 2). The 24 studies reporting on low density lipoprotein cholesterol were pooled using a random effects model because heterogeneity was present. Pooled analyses stratified by dose of alcohol also showed no significant effects of alcohol on low density lipoprotein cholesterol. Pooled analysis of the impact of alcohol by dose on triglycerides showed a significant increase at the highest dose of alcohol (>60 g/day) in the two studies reporting alcohol consumption at this dose: mean difference 0.274 mmol/L (0.043 to 0.505), test for heterogeneity P=0.763 (fig 3).
Fig 3Forest plot of meta-analysis (fixed effects) of effect of alcohol consumption on levels of total cholesterol and triglycerides
The association of alcohol with levels of C reactive protein, interleukin 6, and tumour necrosis factor α was not significant (table 2). Only one study reported that alcohol (in this case beer) increased leucocyte levels in women (0.51 (SD 0.47)×109
/L) but not in men (0.19 (SD 0.31)×109
Fibrinogen levels significantly decreased after alcohol consumption (fig 4 and table 2). Meta-analyses of the remaining haemostatic biomarkers, however, did not show any significant effect of alcohol, including plasminogen activator inhibitor 1 and tissue plasminogen activator antigens (table 2).
Fig 4Forest plot of meta-analysis of effect of alcohol consumption on levels of fibrinogen and adiponectin
Data were insufficient to permit meta-analysis for plasminogen, thromboxane, von Willebrand factor, and e-selectin levels. One study reported a significant increase in plasminogen levels after red wine consumption in 12 men.60
Another study reported a significant decrease in thromboxane levels after both white and red wine consumption.59
The two studies reporting on the effect of alcohol on von Willebrand factor found no significant change in these biomarker levels.54 56
For e-selectin, one study found a significant increase after alcohol consumption,81
whereas another study found no change.38
Three studies reported on the impact of alcohol on intracellular adhesion molecule 1 and two reported on vascular cellular adhesion molecule levels. However, only one study reported data suitable for pooling for each biomarker. Two studies showed no impact of alcohol on intracellular adhesion molecule,37 81
whereas one showed a significant decrease in intracellular adhesion molecule 1 after consumption of red wine but not after gin.38
One study reported no change in vascular cellular adhesion molecule after alcohol consumption,37
whereas another found a significant decrease after consumption of red wine but not after gin.38
Adiponectin levels were consistently significantly increased after alcohol consumption (fig 4). Only two studies reported on the effect of alcohol on levels of leptin; one study found a significant increase after alcohol consumption64
and the other no effect.37
Study quality was analysed using the component approach,13
focusing primarily on study design as the most important quality factor. Sensitivity analyses were stratified by the two major study designs in selected studies (24 crossover studies, 18 before and after studies), with crossover studies being considered the more robust study design. The findings of these stratified sensitivity analyses are in web extra appendix 3 and show generally similar results for both types of study design from analyses that include a sufficient number of studies to yield stable pooled estimates—that is, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and fibrinogen. This sensitivity analysis suggests that, regardless of the study design, alcohol had consistent effects on biomarker levels.
See web extra appendix 4 for additional study quality characteristics. Of the 44 studies meta-analysed, 17 randomised the participants into treatment groups but only one study described the randomisation process. Forty three of the 44 studies described the presence of relevant covariates, such as diet, smoking, and physical activity. Twenty of the studies measured compliance with alcohol consumption, whereas 24 described losses to attrition.
Analyses were also stratified by beverage type (wine, beer, spirits). The results were similar to the combined analyses of all beverage types (see web extra appendix 3).
Evidence of publication bias was assessed for high density lipoprotein cholesterol, apolipoprotein A1, and fibrinogen. No asymmetry was found on visual inspection of the funnel plot for each biomarker, suggesting that significant publication bias was unlikely. This was further confirmed by a non-significant Begg test for each outcome of interest (high density lipoprotein cholesterol P=0.12, apolipoprotein A1 P=0.064, and fibrinogen P=0.88).