Anti-inflammatory effects and safety of omega-3 fatty acids in haemodialysis: a systematic review and meta-analysis.

Abstract

INTRODUCTION: Evidence on the anti-inflammatory effects and safety of omega-3 fatty acid supplementation in haemodialysis (HD) patients remains limited, particularly regarding the influence of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dose, composition, and source. METHODS: We searched PubMed (n=345), CENTRAL (n=148) and EMBASE (n=706) to July 2025. Studies were screened using Covidence, risk of bias was assessed using the Cochrane ROB 1 tool, and analyses were conducted in Review Manager 9.5.1. Only trials reporting C-reactive protein (CRP) were included. Pre-planned subgroup analyses examined formulation type, total daily dose, active ingredient dose, and DHA:EPA composition. Random-effects models were used to generate pooled standardised mean differences (SMDs), with heterogeneity assessed using I2. A sensitivity analysis excluded studies at high risk of bias. The protocol is registered on the Open Science Framework (https://doi.org/10.17605/OSF.IO/JCBHN). RESULTS: Thirteen studies (n=678) were included (12 in meta-analyses). Two studies were judged high risk of bias, one unclear, and the remainder low risk. Adverse events were poorly reported: eight trials did not report any events, while five described only mild, transient effects (e.g., diarrhoea). Omega-3 fatty acids reduced CRP more than comparators across triglyceride formulations (SMD -0.62, 95% CI -1.22 to -0.03; P=0.04, I2=74%); in the <2000 mg/day total dose subgroup (SMD -0.32, 95% CI -0.61 to -0.04; P=0.02, I2=29%); and in the <2000 mg/day active ingredient subgroup (SMD -0.36, 95% CI -0.59 to -0.13; P=0.003, I2=31%). No statistically significant differences were observed between subgroups. Sensitivity analyses did not materially change the results. CONCLUSION: A daily dose <2000 mg of omega-3 fatty acids in natural triglyceride form appears more effective than synthetic ethyl ester formulations for lowering CRP in HD patients. Larger, high-quality trials are required to confirm therapeutic benefit, determine optimal dosing, and clarify the ideal EPA:DHA composition for this population.