Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression

Atherosclerosis. 2015 Aug;241(2):400-8. doi: 10.1016/j.atherosclerosis.2015.05.015. Epub 2015 May 19.


Objective: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial effects on inflammation and cardiovascular disease (CVD). Our aim was to assess the effect of a six-week supplementation with either olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells (PBMC).

Methods: Subjects were sampled at baseline and six weeks after receiving either: olive oil 6.0 g/day (n = 16), EPA 1.8 g/day (n = 16), or DHA 1.8 g/day (n = 18). PBMC were subjected to gene expression analysis by microarray with key findings confirmed by quantitative real-time polymerase chain reaction (Q-PCR).

Results: Plasma phospholipid EPA increased 3 fold in the EPA group, and DHA increased 63% in the DHA group (both p < 0.01), while no effects were observed in the olive oil group. Microarray analysis indicated that EPA but not DHA or olive oil significantly affected the gene expression in the following pathways: 1) interferon signaling, 2) receptor recognition of bacteria and viruses, 3) G protein signaling, glycolysis and glycolytic shunting, 4) S-adenosyl-l-methionine biosynthesis, and 5) cAMP-mediated signaling including cAMP responsive element protein 1 (CREB1), as well as many other individual genes including hypoxia inducible factor 1, α subunit (HIF1A). The findings for CREB1 and HIF1A were confirmed by Q-PCR analysis.

Conclusions: Our data indicate that EPA supplementation was associated with significant effects on gene expression involving the interferon pathway as well as down-regulation of CREB1 and HIF1A, which may relate to its beneficial effect on CVD risk reduction.

Trial registration: ClinicalTrials.gov NCT01400490.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Gene expression; Hypoxia inducible factor 1; Microarray analysis; Peripheral blood mononuclear cells; α subunit.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood
  • Administration, Oral
  • Adult
  • Biomarkers / blood
  • Boston
  • Docosahexaenoic Acids / administration & dosage*
  • Docosahexaenoic Acids / blood
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage*
  • Eicosapentaenoic Acid / blood
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Olive Oil / administration & dosage
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Time Factors
  • Up-Regulation


  • Biomarkers
  • Olive Oil
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PLA2G7 protein, human

Associated data

  • ClinicalTrials.gov/NCT01400490