Role of the EPA: DHA dosing ratio in omega-3 supplements on blood fatty acid profiles and inflammation: a systematic review and meta-analysis

Most omega-3 supplements contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in defined ratios, yet their pharmacokinetic and anti-inflammatory effects are not fully understood. This systematic review and meta-analysis evaluated how EPA:DHA dosing ratios, alongside EPA+DHA daily dose, influence blood fatty acid profiles and inflammatory markers across 96 clinical trials published before February 2025. Standardized mean differences with 95% confidence intervals were calculated. EPA+DHA supplementation significantly increased EPA:DHA blood ratios and blood EPA+DHA levels, with larger effects in healthy individuals. Supplementation also reduced arachidonic acid (AA) and key inflammatory markers, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), particularly in participants with underlying health conditions. Ratios <1.0 produced the greatest cytokine reductions, whereas ratios ≥1.0 most effectively increased the EPA:DHA blood ratio and lowered AA. EPA+DHA doses of 1-3 g/day were associated with the most consistent reductions in CRP, TNF-α, and IL-6. Linear regression showed a strong association between the EPA:DHA dosing ratio and the EPA:DHA blood ratio and identified the EPA:DHA blood ratio as the strongest predictor of AA reduction. These findings indicate distinct ratio- and dose-dependent effects of EPA and DHA and highlight the importance of optimizing omega-3 formulations to enhance bioavailability and anti-inflammatory outcomes.