Metabolomics in the study of alcohol use disorder: a systematic review.

BACKGROUND: Alcohol Use Disorder (AUD) is linked to multiple medical conditions, partly due to ethanol's toxic effects, which disrupt a wide range of molecular compounds. Metabolome research provides crucial insights that can improve the understanding and management of AUD and alcohol-related harm. This systematic review synthesizes recent evidence on metabolomic disturbances in individuals with alcohol use, risky alcohol consumption, and AUD. METHODS: A PRISMA-guided systematic review was conducted up to January 31, 2024, across PubMed, Scopus, and PsycInfo. Articles meeting the following criteria were included: 1) observational studies or randomized controlled trials on individuals with AUD, risky alcohol use, or alcohol use; 2) studies describing alcohol use patterns (amount/frequency); 3) studies reporting metabolic measures across major biological pathways. Metabolomic analyses across different body sites, not limited to plasma or serum, were surveyed. RESULTS: The review included 36 studies (26,625 individuals), revealing consistent metabolic disturbances related to alcohol use and AUD. Key findings included altered amino acid metabolism, with elevated cysteine and glutamate, reduced citrate, and variable leucine, tyrosine, valine, and serotonin metabolites. Lipid metabolism showed increased fatty acids (saturated, monounsaturated, omega-3), upregulated phosphatidylcholines, and downregulated sphingomyelins. Nucleic acid metabolites (hypoxanthine, pyrimidine) were notably increased. Carbohydrate metabolism data remained scarce, highlighting a research gap. CONCLUSION: Amino acid and fatty acid disturbances were the most pronounced, suggesting their potential role in AUD development and progression. These findings indicate that metabolomic profiling may provide useful information on the severity and pattern of alcohol use. While preliminary, this approach could, in the future, contribute to more individualized prevention and treatment strategies in AUD.