The Impact of Omega-3 Fatty Acids on Triglyceride Levels in Patients with Metabolic Dysfunction–Associated Steatotic Liver Disease: A Meta-Analysis of Randomized Controlled Trials with Subgroup Analysis by Diabetes Status

Lan Li,1,* Cong Cong,2,3,* Xiaolan Zhang,4 Xiaoxia Zhang3 1Department of Traditional Chinese Medicine, Taiping Sub-District Community Health Service Center, Jinan, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4Department of Pediatrics, Third People’s Hospital of Liaocheng, Liaocheng, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoxia Zhang, Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, No. 4655, University Road, University Science Park, Changqing District, Jinan, Shandong, People’s Republic of China, Email zxx_9137@163.comBackground: 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.Keywords: metabolic dysfunction–associated steatotic liver disease, omega-3 polyunsaturated fatty acids, triglycerides, type 2 diabetes