Abstract
BACKGROUND: Alcoholic liver disease (ALD) is a major global cause of liver-related morbidity and mortality, driven by excessive alcohol consumption and characterized by oxidative stress, inflammation, disordered lipid metabolism, and gut-liver axis dysfunction. Oyster-derived bioactive compounds have shown hepatoprotective potential in experimental settings; however, their efficacy and role in ALD management remain unclear. OBJECTIVE: To systematically evaluate and synthesize preclinical and clinical evidence on oyster-derived bioactive compounds for the prevention and treatment of ALD. METHODS: PubMed, Web of Science, and Scopus were searched for studies examining oyster-derived bioactives, including polysaccharides, peptides, protein hydrolysates, and related extracts, in alcohol-induced liver injury models. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using the SYRCLE tool for animal studies and RoB 2.0 for human trials. Certainty of evidence was evaluated using the GRADE framework. RESULTS: Eleven studies met the inclusion criteria, comprising ten animal studies and one randomized controlled trial. In animal models, oyster-derived interventions reduced alanine and aspartate aminotransferase levels by approximately 34-56%, increased antioxidant defenses (glutathione and superoxide dismutase increased by up to 45% and 40%, respectively), and decreased inflammatory mediators including TNF-α, IL-1β, and IL-6. Improvements in lipid metabolism and gut-liver axis markers were also reported in several studies. The single human trial demonstrated a modest reduction in γ-glutamyl transferase, with no significant changes in ALT or AST. Overall, the certainty of evidence ranged from very low to low, reflecting methodological heterogeneity, risk of bias, and limited human data. CONCLUSIONS: Oyster-derived bioactives consistently demonstrate hepatoprotective effects in preclinical models of ALD through antioxidant, anti-inflammatory, metabolic, and gut-mediated mechanisms. However, the current evidence base is preliminary, and well-designed, adequately powered clinical trials are required to determine their clinical efficacy, optimal formulation, and long-term safety. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251104584, identifier CRD420251104584.