Meta-analysis2026

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

Khabir Z, Abdelhafez A, Camponovo F, Joyce P, Garcia-Bennett A

Critical reviews in food science and nutrition · 1 citation

How it was studied

Design
Meta-analysis (indexed by PubMed)
Studied in
People
Main outcome
Health markers and function

Who paid for it

Funding
Independent funding
Government
Australian Research Council Industrial Transformation Training Centre for Facilitated Advancement of Australia’s Bioactives

Based on 1 listed funder(s).

Publication

Published
2026-01-22 · Crit Rev Food Sci Nutr · vol. 66 · issue 20 · pp. 3866–3887
Publisher
Taylor & Francis
Cited
5 citations · more than 99% of similar papers · 14.1× the field average
Impact
Top 10% most cited in its field
References
162 works
Access
Paywalled
Research areas
Fatty Acid Research and Health · Eicosanoids and Hypertension Pharmacology · Vitamin K Research Studies
Keywords
Dosing, Docosahexaenoic acid, Eicosapentaenoic acid, Bioavailability, Pharmacokinetics, Whole blood, Arachidonic acid, Fatty acid
MeSH
humans, inflammation, docosahexaenoic acids, eicosapentaenoic acid, fatty acids, arachidonic acid, tumor necrosis factor-alpha, c-reactive protein, anti-inflammatory agents, interleukin-6, dietary supplements, biomarkers

5 authors

From AU

  • Zahra Khabir · correspondingAustralian Research Council; Macquarie University
  • Amer AbdelhafezAustralian Research Council; University of South Australia
  • Fabrizio F. CamponovoAustralian Research Council
  • Paul JoyceAustralian Research Council; University of South Australia
  • Alfonso Garcia-BennettAustralian Research Council; Macquarie University

Abstract

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.

Abstract via Europe PMC. Copyright remains with the authors or publisher.

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