Recent advances in alcohol metabolism: from the gut to the brain
Open accessAbstract
Globally, alcohol is the most widely used psychoactive drug and a leading cause of premature death among individuals aged 15–49 years. Understanding the absorption, distribution, metabolism, and excretion of alcohol in the human body, otherwise known as alcohol pharmacokinetics, is essential for predicting its behavioral effects and toxic consequences. This review examines the evolutionary origins of alcohol consumption and metabolism, focusing on the activity of alcohol dehydrogenase enzymes across species, which serve as key catalysts in alcohol oxidation. It also highlights recent advances in understanding central alcohol metabolism and updates on the potential clinical significance of nonoxidative pathways of alcohol metabolism and endogenous alcohol production, particularly in the context of liver disease. In addition, the review inspects factors that modulate alcohol metabolism, including genetic polymorphisms, biological sex, food intake, women’s reproductive status, and clinical interventions such as medications and metabolic surgeries. Understanding these sources of variability in alcohol metabolism is crucial for identifying individual risk factors and tailoring strategies to reduce alcohol-related harm. This comprehensive review offers a current perspective on alcohol pharmacokinetics, valuable insights into its implications for health, behavior, and potential innovative therapeutic targets.
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References 290 · Cited by 34
- Authors
- Goldman, M. R., Molina-Castro, M., Etkins, J. C., Koide, T. L., Ramchandani, V. A., Plawecki, M. H., Mennella, J. A., & Pepino, M. Y.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- University of Illinois at Urbana-Champaign
- Indiana University School of Medicine (US)
- Istituto Superiore di Sanità (IT)
- Monell Chemical Senses Center (US)
- Corresponding author
- Pepino, Marta Yanina
- ORCID
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2025-10-01
- Volume
- 105
- Issue
- 4
- Pages
- 2501-2535
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- PMC
- PMC12345593
- OpenAlex
- W4412158922
- Cited by
- 34
- References
- 290
- Citations by year
- 2026: 27 · 2025: 7
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- HHS | NIH | National Institute on Alcohol Abuse and Alcoholism (AA024103, AA007611, AA027236, Z1AAA000466)
- HHS | NIH | National Institute on Deafness and Other Communication Disorders (DC011287)
- HHS | NIH | National Institute on Drug Abuse (AA008401T)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcohol metabolism, alcohol pharmacokinetics, alcohol dehydrogenase, liver disease, genetic polymorphism, sex differences, dietary intake, reproductive status, metabolic surgery, alcohol-related harm
- MeSH terms
- Alcohol Dehydrogenase, Alcohol Drinking, Ethanol, Animals, Brain, Humans, Gastrointestinal Tract
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