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.
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.


OBJECTIVE
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.


METHODS
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.
Institute of Nutrition and Functional Foods, Pavillon des Services.
Janie
J
Allaire
Institute of Nutrition and Functional Foods, Pavillon des Services, University Hospital Center (CHU) of Québec Research Center, and.
Patrick
P
Couture
Institute of Nutrition and Functional Foods, Pavillon des Services.
Myriam
M
Leclerc
Institute of Nutrition and Functional Foods, Pavillon des Services.
Amélie
A
Charest
Institute of Nutrition and Functional Foods, Pavillon des Services.
Johanne
J
Marin
Institute of Nutrition and Functional Foods, Pavillon des Services.
Marie-Claude
MC
Lépine
University Hospital Center (CHU) of Québec Research Center, and Department of Social and Preventive Medicine, Laval University, Quebec, Canada; and.
Denis
D
Talbot
Institute of Nutrition and Functional Foods, Pavillon des Services, University Hospital Center (CHU) of Québec Research Center, and Quebec Heart and Lung Institute, Quebec, Canada.
André
A
Tchernof
Institute of Nutrition and Functional Foods, Pavillon des Services, benoit.lamarche@fsaa.ulaval.ca.
Benoît
B
Lamarche
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D052242:Adiponectin; D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D002097:C-Reactive Protein; D002784:Cholesterol; D015118:Eicosapentaenoic Acid
DHA; EPA; inflammation; men and women; randomized controlled trial; risk factors