Dietary Omega-3 Fatty Acids from Fish and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Mediterranean Population: Findings from the NUTRIHEP Cohort.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is linked to metabolic syndrome, obesity, and type 2 diabetes. Omega-3 fatty acids, especially EPA and DHA from fish, may protect against hepatic steatosis. Methods: From 2015 to 2018, all participants were invited to the first follow-up, where 1426 (62% response rate) responded and underwent the same standardized protocol as at baseline. For this analysis, the study is a cross-sectional investigation focusing solely on follow-up data, which included 1297 adults. MASLD was diagnosed via standardized ultrasound, and dietary intake was assessed using the validated EPIC Food Frequency Questionnaire. Associations between total EPA and DHA intake and MASLD were examined using logistic regression models adjusted for age, sex, marital status, occupation, income, Mediterranean diet adherence, liver enzymes, and C-reactive protein. Results: Overall, 48.5% of participants had MASLD. Higher total EPA and DHA intake was associated with lower odds of MASLD (EPA highest vs. lowest quartile: OR = 0.572, 95% CI 0.400-0.818; DHA highest vs. lowest quartile: OR = 0.516, 95% CI 0.361-0.739). Intake of fatty fish contributed most strongly to this protective effect (EPA highest vs. lowest quartile: OR = 0.556, 95% CI 0.390-0.794; DHA highest vs. lowest quartile: OR = 0.575, 95% CI 0.403-0.820), whereas mollusks, crustaceans, and some processed/frozen fish showed weaker or no associations. A statistically significant trend of decreasing MASLD risk was observed across increasing quartiles of both EPA and DHA intake. Conclusions: Higher intake of EPA and DHA, especially from fatty fish, is linked to lower MASLD risk in this Mediterranean population, supporting recommendations for regular fish consumption to protect liver health.