To establish a causative relationship between a given risk factor and an outcome, several conditions must be met. Among them, temporal relationship, strength and dose-response of association, consistency, specificity, and, very importantly, biological plausibility. A statistical association alone is certainly insufficient,[1] especially when it comes to relationships between risk factors and outcomes that have not been already observed in randomized clinical trials, but are based solely on observational studies. This is the case with the longstanding debate on the relationship between alcohol consumption and health, an issue for which there is a lack of large randomized clinical trials because they are difficult to implement.[2] Therefore, the available scientific evidence is presently based on a great number of generally well-performed observational studies that have assessed both the harmful effects of nonmoderate alcohol consumption and the protective effects of low consumption, especially in relation to cardiovascular health.[3,4]
To shed light on the relationship between alcohol consumption and health, it is crucial to elucidate the underlying mechanisms (biological plausibility) that determine how alcohol may affect our health. One specific question of interest is how light/moderate alcohol consumption might exert the cardiovascular protection that many, although not all, observational studies have shown. Identified mechanisms, including increase of high-density lipoprotein, anti-inflammatory and antioxidant effects, and improved blood flow, do not seem to be entirely exhaustive or convincing.[5]
A new study published in this issue of the Journal of the American College of Cardiology[6] appears to suggest a new, interesting direction. This study aimed to investigate whether the association between light/moderate alcohol consumption and lower risk of major adverse cardiovascular events (MACE) is mediated by decreased stress-related neural network activity. Neural control of the heart involves continuous modulation of cardiac mechanical and electrical activity to meet the organism's demand for blood flow. The closed-loop control scheme consists of interconnected neural networks with central and peripheral components working cooperatively with each other. These components cooperate to control various aspects of cardiac function, which produce measurable "functional" outputs such as heart rate and blood pressure.[7]
The researchers analyzed data from 713 participants enrolled in the Mass General Brigham Biobank who completed a health behavior survey and underwent brain imaging.[6] Light/moderate alcohol consumption was found to be associated with lower MACE risk, and this was partially mediated by decreased stress-related neural network activity. The authors concluded that light/moderate alcohol consumption associates with reduced MACE risk by lowering the activity of a brain network already known for its association with cardiovascular disease.[8]
The results of this study well align with several previous studies that have reported a positive role of light/moderate alcohol consumption in neuroprotection.[9] Several studies have observed that moderate alcohol consumption is associated with a lower risk of cognitive decline and dementia, better cognitive function, and reduced brain atrophy, suggesting that alcohol may play a protective role in brain function by promoting neural plasticity.[10,11] Although the mechanisms underlying these neuroprotective effects are not fully understood, they may be related to the antioxidant and anti-inflammatory properties of certain compounds found in alcoholic beverages, especially in wine, such as resveratrol and flavonoids.[12] These compounds have been shown, in experimental systems, to protect against oxidative stress and inflammation, which can contribute to neuronal damage and cognitive decline.[9–11] However, it is important to underline that excessive or irregular (binge) alcohol consumption has detrimental effects on brain health and increases the risk of cognitive impairment and dementia.[12,13] As such, moderation is the key when discussing about alcohol consumption and health.[3,14]
In conclusion, the discovery of a new possible mechanism of action suggests that moderate alcohol consumption can improve cardiovascular health by lowering the activity of a brain network associated with cardiovascular disease: a stimulating link among alcohol, brain, and the heart that deserves closer attention in future investigations. The study by Mezue et al,[6] although not a randomized clinical trial, uses a different original approach to further support many previous observational studies showing that light/moderate alcohol consumption reduces the global risk of cardiovascular disease.[4,14,15] However, we wish to insist that individuals consuming alcohol do not exceed the recommended daily dose limits suggested in many countries and that no abstainer should start to drink, even in moderation, solely for the purpose of improving his/her health outcomes.
J Am Coll Cardiol. 2023;81(23):2326-2327. © 2023 American College of Cardiology Foundation
