Exercise as a Multisystem Adjunct for Alcohol-Associated Liver Disease: Inflammatory Mechanisms, Muscle-Liver Crosstalk, and Translational Gaps.

Background

Alcohol-associated liver disease (ALD) involves ethanol-related metabolic injury, inflammation, gut-liver dysfunction, and progressive loss of skeletal muscle and functional reserve. Exercise could influence several of these pathways, but ALD-specific evidence remains limited. We therefore evaluated exercise as an adjunct, not a substitute for established care, across the ALD spectrum.

Methods

We conducted a structured narrative review of PubMed/MEDLINE, Google Scholar, and publisher records updated through 20 August 2026. Evidence was classified as direct human ALD/MetALD evidence, direct preclinical alcohol-injury evidence, indirect clinical evidence from MASLD or mixed-etiology cirrhosis, or mechanistic evidence from broader exercise biology.

Results

Direct human evidence is predominantly observational. Leisure-time physical activity is associated with lower liver mortality across drinking patterns and with lower odds of at-risk advanced fibrosis in MetALD/ALD. These associations do not establish the efficacy of structured exercise training. Preclinical alcohol-injury models support redox- and Nrf2-mediated hepatoprotection, whereas proposed effects on AMPK-SIRT1-PGC-1α signaling, mitochondrial quality, gut microbial metabolites, myokines, and ammonia handling remain largely extrapolated. Metabolomic studies identify disturbances in redox balance, lipid intermediates, acylcarnitines, bile acids, and amino acid and tryptophan metabolism. These alterations provide candidate endpoints for future trials. Myostatin and decorin are associated with ALD severity, but their responsiveness to exercise is unknown. We therefore propose a stage-specific research and practice framework with explicit safety considerations.

Conclusions

Exercise is a promising but unproven multisystem adjunct for ALD. It should complement abstinence support, alcohol use disorder care, nutrition, and standard medical management. ALD-specific trials should integrate metabolomics, liver outcomes, functional measures, sex, alcohol exposure, disease stage, and adverse events.