A mechanistic perspective on the health promoting effects of alcohol - A focus on epigenetics modification

An opinion article published in the journal Alcohol establishes a possible role of ethanol-derived acetate in achieving homeostasis (a state of balance among all the body systems needed for the body to survive and function correctly) and sustaining an organism’s health span. While the detrimental effects of binge drinking are well recognised, low-to-moderate alcohol consumption may be beneficial to health, although the underlying mechanism(s) remains elusive.
The authors examine the effects of low dose alcohol consumption from the perspective of epigenetic modulation. Biochemically, alcohol is metabolised into acetate and subsequently to acetyl-coA, which can modulate histone acetylation levels. While elevated levels of acetyl-CoA are detrimental for longevity, the authors argue that diminished acetyl-CoA also negatively affects fatty acid biosynthesis and histone acetylation, which play a critical role in gene expression and, ultimately, health span. Since mitochondrial function and glucose metabolism, which provide the main source of nucleocytoplasmic acetyl-CoA, are compromised with age, alcohol-derived acetate could be an alternative source of acetyl-CoA to compensate. Hence, the health benefits of low ethanol consumption may be more pronounced after midlife, since mitochondrial function and/or glucose metabolism are diminished in this phase of the life course. Indeed, various clinical alcohol consumption studies concur with this notion, and have shown that a low dose of regular alcohol intake after midlife brings about various health and survival benefits.
The requirement for regular alcohol intake may also reflect the transient nature of ethanol-induced histone acetylation. Conversely, ethanol may also stimulate carcinogenesis by inhibiting DNA methylation, as it was shown to reduce various pathways leading to DNA and histone methylation. However, unlike acetylation, where ethanol directly increases the substrate for acetylation, this effect was only observed in the high alcohol exposure cohort. While alcohol-derived acetate may be beneficial for health after midlife, various detrimental effects of alcohol consumption remain, and hence, the authors state that they do not advocate excessive drinking to increase acetate.
Source: an SP, Kumar SN, Fann DY, Kennedy BK. A mechanistic perspective on the health promoting effects of alcohol - A focus on epigenetics modification. Alcohol. 2023 Mar;107:91-96.