{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:55:15Z","timestamp":1790564115357,"version":"4.1.0"},"reference-count":287,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>Alcohol metabolism is a multi-step biochemical process driven primarily by hepatic oxidation of ethanol to acetaldehyde and then to acetate. Although this pathway protects the body from prolonged ethanol exposure, transient acetaldehyde accumulation generates substantial toxicity, and chronic alcohol intake activates auxiliary pathways that amplify oxidative stress, inflammation, and tissue injury. Both metabolic capacity and physiological response to alcohol vary widely between individuals, reflecting genetic and epigenetic variation in the alcohol- and aldehyde-dehydrogenase enzymes, the cytochrome P450 system, and modulating factors such as sex, age, body composition, nutrition, and overall health. In this review we consolidate 3\u00a0decades of biochemical, clinical, and epidemiological evidence into an integrated picture of alcohol\u2019s effects on the liver, brain, and other organ systems, with attention to oxidative stress, neurochemistry, glycoconjugate biology, and the convergence of alcohol- and metabolic-driven liver disease. We also examine recent advances in the treatment of alcohol use disorder (AUD) - including incretin-based pharmacotherapies, ketamine-assisted therapy, focused ultrasound neuromodulation, exercise interventions, and combination drug regimens - and we critically evaluate ongoing controversies surrounding moderate drinking, resveratrol, and the use of heterogeneous non-drinker comparison groups in observational studies. Finally, we discuss the changing social context of drinking, the role of endogenous ethanol\/acetaldehyde systems in stress resilience across species, and the implications of these insights for personalized prevention and risk-reduction strategies. We conclude by proposing an exposure-susceptibility-context model that integrates the principal determinants of alcohol-related harm.<\/jats:p>","DOI":"10.3389\/ftox.2026.1876876","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:03:20Z","timestamp":1790561000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Alcohol consumption: from biochemistry to behavior, health, and beyond"],"prefix":"10.3389","volume":"8","author":[{"given":"Evgeny","family":"Pechkovsky","sequence":"first","affiliation":[{"name":"Research Institute of Molecular Biology and Biophysics, Federal State Budgetary Scientific Institution \u201cFederal Research Center for Fundamental and Translational Medicine\u201d","place":["Novosibirsk, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Kershengoltz","sequence":"additional","affiliation":[{"name":"Institute of Biological Problems of the Cryolithozone, Siberian Branch of the Russian Academy of Sciences","place":["Yakutsk, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin V.","family":"Vlassov","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology and Fundamental Medicine SB RAS","place":["Novosibirsk, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliy","family":"Vlassov","sequence":"additional","affiliation":[{"name":"Higher School of Economics","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Turchinovich","sequence":"additional","affiliation":[{"name":"Department of Medicine VI, University Medical Centre Mannheim, Heidelberg University","place":["Mannheim, Germany"]},{"name":"Heidelberg Biolabs GmbH","place":["Heidelberg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1002\/hep.23535","article-title":"Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease","volume":"51","author":"Abdelmalek","year":"2010","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1021\/jf950807o","article-title":"Induction of phytoalexin (resveratrol) synthesis in grapevine leaves treated with aluminum chloride (AlCl3)","volume":"44","author":"Adrian","year":"1996","journal-title":"J. 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