A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study
Open accessAbstract
Background To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions.Objectives We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease.Design In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA.Results Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046).Conclusions DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.
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In a small trial, DHA increased LDL-C, LDL particle size, and HDL2, but EPA did not.
“In this trial, DHA increased LDL-C, LDL particle size, and HDL2, but EPA did not.62”
From Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association (2019) · cites this paper as [62]
The Blood lipids section reports that DHA increased LDL-C more than EPA, but EPA also significantly increased LDL-C versus control (+2.2%). The LCn-3PUFA and plasma lipids section says increased LDL particle size with DHA was an inference requiring measurement. The paper reports increased HDL cholesterol, not specifically HDL2. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThat trial reported an inverse relationship between triglyceride values and LDL particle size, and a positive correlation between HDL-C and LDL particle size.
“This trial also reported an inverse relationship between triglyceride values and LDL particle size, whereas HDL-C was positively correlated with LDL particle size.”
From Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association (2019) · cites this paper as [62]
The ‘LCn-3PUFA and plasma lipids’ discussion (page unavailable) says that lower triglycerides after DHA supplementation suggest larger LDL particles, but explicitly says this assumption needs verification by measuring LDL particle size. The Blood lipids results (page unavailable) report higher HDL cholesterol with DHA, not a positive correlation between HDL-C and LDL particle size. The trial therefore did not report either correlation as claimed. (LLM, conf=0.86)
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- Authors
- Allaire, J., Couture, P., Leclerc, M., Charest, A., Marin, J., Lépine, M.-C., Talbot, D., Tchernof, A., & Lamarche, B.
- Affiliations
- Institut sur la nutrition et les aliments fonctionnels (INAF) (CA)
- Université Laval (CA)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 104
- Issue
- 2
- Pages
- 280-287
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2480176085
- Cited by
- 252
- References
- 31
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 25 · 2023: 18 · 2022: 28 · 2021: 37 · 2020: 37 · 2019: 24 · 2018: 17 · 2017: 26 · 2016: 7 · 2015: 1
- FWCI
- 25.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (123494_1)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Keywords
- omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, fish oil supplementation, inflammatory markers, IL-18, adiponectin, C-reactive protein, interleukin-6, TNF-α, triglycerides, HDL cholesterol, LDL cholesterol, abdominal obesity, cardiovascular risk, sex differences
- MeSH terms
- Adult, Aged, C-Reactive Protein, Cholesterol, Docosahexaenoic Acids, Double-Blind Method, Female, Humans, Inflammation, Male, Middle Aged, Triglycerides, Tumor Necrosis Factor-alpha, Eicosapentaenoic Acid, Biomarkers, Cytokines, Cross-Over Studies, Dietary Supplements, Interleukin-18, Adiponectin
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