Recent advances in alcohol metabolism: from the gut to the brain

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.