This systematic review and meta-analysis examined the anti-inflammatory effects and safety of omega-3 fatty acid supplementation in 678 haemodialysis patients. The analysis compared omega-3 supplementation to unspecified comparators, with C-reactive protein (CRP) as the primary outcome.
In specific subgroup analyses, omega-3 fatty acids reduced CRP more than comparators. For triglyceride formulations, the standardized mean difference (SMD) was -0.62 (95% CI -1.22 to -0.03; P = 0.04). For total daily doses below 2000 mg, SMD was -0.32 (95% CI -0.61 to -0.04; P = 0.02). For active ingredient doses below 2000 mg/day, SMD was -0.36 (95% CI -0.59 to -0.13; P = 0.003).
Safety data were limited. Eight trials did not report adverse events, while five described only mild, transient effects such as diarrhea. Serious adverse events, discontinuations, and tolerability were not reported.
Key limitations include substantial heterogeneity in the triglyceride formulation analysis (I² 74%), with lower heterogeneity in dose subgroups (I² 29-31%). Two studies were judged high risk of bias, and one unclear. The evidence suggests a daily dose below 2000 mg in natural triglyceride form may be more effective than synthetic ethyl ester formulations for lowering CRP, but this remains an association requiring confirmation.
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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 I. 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, I = 74 %); in the <2000 mg/day total dose subgroup (SMD -0.32, 95 % CI -0.61 to -0.04; P = 0.02, I = 29 %); and in the <2000 mg/day active ingredient subgroup (SMD -0.36, 95 % CI -0.59 to -0.13; P = 0.003, I = 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.