The Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiometabolic Risk Factors: A Systematic Review

Int J Mol Sci. 2018 Feb 9;19(2):532. doi: 10.3390/ijms19020532.


A large body of evidence supports the cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). There is increasing interest in the independent effects of EPA and DHA in the modulation of cardiometabolic risk factors. This systematic review aims to appraise the latest available evidence of the differential effects of EPA and DHA on such risk factors. A systematic literature review was conducted up to May 2017. Randomised controlled trials were included if they met strict eligibility criteria, including EPA or DHA > 2 g/day and purity ≥ 90%. Eighteen identified articles were included, corresponding to six unique studies involving 527 participants. Both EPA and DHA lowered triglyceride concentration, with DHA having a greater triglyceride-lowering effect. Whilst total cholesterol levels were largely unchanged by EPA and DHA, DHA increased high-density lipoprotein (HDL) cholesterol concentration, particularly HDL₂, and increased low-density lipoprotein (LDL) cholesterol concentration and LDL particle size. Both EPA and DHA inhibited platelet activity, whilst DHA improved vascular function and lowered heart rate and blood pressure to a greater extent than EPA. The effects of EPA and DHA on inflammatory markers and glycaemic control were inconclusive; however both lowered oxidative stress. Thus, EPA and DHA appear to have differential effects on cardiometabolic risk factors, but these need to be confirmed by larger clinical studies.

Keywords: cardiometabolic risk factor; docosahexaenoic acid; eicosapentaenoic acid; omega-3 polyunsaturated fatty acids; systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antioxidants / therapeutic use*
  • Docosahexaenoic Acids / therapeutic use*
  • Eicosapentaenoic Acid / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / prevention & control*
  • Randomized Controlled Trials as Topic


  • Antioxidants
  • Hypoglycemic Agents
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid