Ischemic heart disease (IHD) is the leading cause of death and disease burden in the US [
1], Europe [
2], and globally [
3],[
4], and alcohol consumption is one of the leading risk factors for mortality and morbidity [
5],[
6]. There are well-established risks from neuro-toxic, hepato-toxic, and carcinogenic effects caused by alcohol consumption (for example, the risk for cancers of the upper aerodigestive tract [
7]-[
9], injuries [
6],[
10], and liver cirrhosis [
6],[
10],[
11]). However, there has been much debate about a beneficial effect of alcohol consumption on IHD [
12]-[
14]. High prevalence of both exposure and disease make this question a frequent topic among general practitioners, researchers, media, and the public. Aside from numerous individual studies, several meta-analyses published in the last decade have summarized the association between alcohol consumption and IHD risk.
Most meta-analyses of epidemiological data have shown a mix between a beneficial and detrimental association from alcohol consumption on IHD that depends on the level of average consumption. This relationship is most often described as curvilinear, or `J-shaped’ [
15],[
16], but also sometimes as a flattened-out inverse association [
15],[
17],[
18]. The specific shape of the risk curve seems to depend at least on sex and IHD outcome (mortality versus morbidity). Findings of a beneficial effect are supported by a substantial number of short-term experimental studies on the effect of alcohol consumption on several surrogate biomarkers for IHD in a dose-dependent relationship [
19],[
20], including improved lipid profiles, inhibition of platelet activation, reduction of fibrinogen levels, and anti-inflammatory effects. In particular, high density lipoprotein (HDL) cholesterol levels have a clear dose-response relationship with alcohol consumption, with the highest levels observed in people with the highest alcohol consumption [
21],[
22]. Many criticisms have arisen over the last three decades questioning the relationship found in epidemiological studies because of limited quality of alcohol assessment, the influence of drinking pattern, adjustment for confounding, or the inability for observational studies to determine causality [
13],[
23]. Although criteria for a causal relationship [
24] seem to be fulfilled (see also [
15],[
18]), a direct link for alcohol consumption on IHD risk from long-term randomized trials is currently, and for the foreseeable future, missing. Thus, epidemiological studies, as is the case for many other IHD risk factors, play an important role in assessing the role of alcohol consumption on disease risk. The objective of this review is to examine the evidence available to define the relationship between alcohol consumption and IHD based mainly on systematic reviews and meta-analyses, with a focus on the reference group (that is, the use of lifetime abstainers and not current abstainers as the reference group because of the `sick-quitter’ effect [
25]); the influence of drinking pattern (in particular episodic heavy drinking among on average moderate drinkers [
26]); and the influence of several other important risk factors for IHD, such as age, smoking status, physical activity, and body mass index (BMI), all of which might confound risk estimates for alcohol.