Abstract
BACKGROUND: The rising global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) necessitates effective therapies. This meta-analysis therefore assesses the efficacy of omega-3 PUFAs in reducing triglycerides in MASLD patients and examines how diabetes status modulates this effect. PURPOSE: To resolve existing uncertainties, this systematic review and meta-analysis was conducted to evaluate the efficacy of omega-3 PUFAs in reducing TG among MASLD patients, with a prespecified analysis to elucidate the role of diabetes status. PATIENTS AND METHODS: We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library (up to Sep 22, 2025) for randomized controlled trials assessing omega-3 PUFA supplementation on triglyceride levels in MASLD patients, with subgroup analysis by diabetes status. RESULTS: Pooled data from 9 studies (n=528) revealed that omega-3 PUFA supplementation was associated with a significant reduction in triglyceride (TG) levels in MASLD patients (MD: -13.81 mg/dL; 95% CI: -24.56, -3.06); however, considerable heterogeneity (I²=22.5%) suggests that the true effect may be inconsistent across different patient populations. Subgroup analysis delineated a stark contrast: while a beneficial effect was confirmed in non-diabetic MASLD patients (MD: -15.78 mg/dL), it was absent in those with comorbid type 2 diabetes (P = 0.33). Meta-regression further confirmed that the prevalence of diabetes within study populations did not linearly influence the TG-lowering outcome (P = 0.752). Finally, the intervention showed no significant impact on other metabolic parameters such as ALT, HDL, or LDL. CONCLUSION: This meta-analysis suggests that omega-3 fatty acids are associated with reduced TG levels in MASLD patients on average, but the effect is inconsistent and influenced by diabetes status. The non-significant effect in diabetic patients and the wide prediction intervals call for caution in interpreting these findings, and further research is needed to identify subgroups that may benefit.