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

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.