Is Alcohol Healthy? The Saga Continues

There have been a fair number of epidemiological trials that show light (up to 2/day) to moderate (up to 4/day) drinking is associated with reduced risk of coronary heart disease (CHD) and increased longevity [1,2,3]. Anything above 4 drinks a day and you are increasing your risk of cancer, liver disease, stroke, etc [1]. This is what we call a J-shaped curve. At a lower dose, we see benefits. But as the dose gets higher we see relative risk increase.

But these trials don’t actually prove alcohol reduces certain risk factors, it only shows us an association that should be looked into further. Enter the latest study [4]:

CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study

Published in the journal Alcohol (yes, that’s an actual journal), the study asserts that the “cardioprotective effect of alcohol may be restricted to subjects with a particular genotype of the cholesteryl ester transfer protein (CETP) polymorphism.”

Let’s break down the paper. For science!

This was a population-based case-control study. This means that the study pulled patients who did have a disease or certain outcome (cases) and compared them with patients that did not have a disease or outcome (controls). Researchers will then look back and try and determine the relationship between a risk factor and a disease [10]. In this article, we’re looking at the relationship between alcohol, the B2B2 CETP TaqIB genotype, and cardiovascular heart disease. The study randomly selected people from southern Sweden between the ages of 25-74. 618 (453 men and 165 women) in the cohort had experienced a myocardial infarction, unstable angina, or had been diagnosed with coronary heart disease. Another 2,921 (1,378 men and 1,543 women) had been deemed healthy and were the control for this study. The control group was asked about the frequency of their intake of different kinds of alcoholic beverages in the past 12 months and the case group was asked about their alcohol intake in the 12 months prior to their latest coronary event.

It is very important to note that these were self-reported alcohol intake numbers, meaning the accuracy of the data is, as we say in science, ‘sketchy’. Do you remember the frequency and types of alcohol you have imbibed over the past year?

Blood samples were taken from everyone to assess cholesterol and triglyceride concentrations (using enzymatic assays) and HDL concentrations were also measured. Genotyping was performed to see if patients possessed the B2B2 variation of the CETP gene. This gene had been looked at in a few other papers as the possible mechanism for the cardioprotective benefits of alcohol, but the results thus far have been mixed [5,6,7,8]. The working theory is that low levels of alcohol indirectly raise HDL levels via the CETP TaqIB gene, which is partly responsible for the regulation of HDL.

The researchers found that patients that carried the B2B2 genotype saw the greatest reductions in their risk for coronary artery disease. Just to put that into perspective, of the 3,539 patients only 659, or 18.62%, tested positive for the B2B2 genotype. Those lucky few that did possess this gene saw their heart disease risk drop by 79%. On the upside, those that did not have this magical gene still saw an overall risk reduction of 20% with moderate alcohol consumption.

So what is this gene doing that causes this precipitous drop in CHD risk? In a word, they do not know. But they don't think it’s because of the CETP-Alcohol-HDL interaction.

The cardioprotective effect of alcohol in the CETP TaqIB B2 homozygotes could not be explained by a mediating effect of HDL-cholesterol or an interaction between HDL-cholesterol and genotype, nor was the effect reduced after adjustment for different socioeconomic and lifestyle variables, or explained by selective survival of certain genotype groups. The finding that the protective effect of alcohol is not due to HDL-cholesterol is consistent with the results in a recent Norwegian study (Magnus et al., 2011).

So what does this all mean for your alcohol consumption? Study author Dag S. Thelle puts it best, [9]

In my view, there is not [a message for drinkers]. Not at this time. It’s far too early to say anything. The study is too small and has to be repeated.

And that is how science goes. Sometimes the knowledge we acquire is outpaced by the rate at which we come up with new questions.