Fish oil and vascular endothelial protection: bench to bedside

Free Radic Biol Med. 2012 Jul 15;53(2):271-9. doi: 10.1016/j.freeradbiomed.2012.05.005. Epub 2012 May 12.


Fish oil is recommended for the management of hypertriglyceridemia and to prevent secondary cardiovascular disorders. Fish oil is a major source of ω-3-polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Clinical studies suggest that fish oil not only prevents the incidence of detrimental cardiovascular events, but also lowers the cardiovascular mortality rate. In addition to a classic lipid-lowering action, ω-3-PUFAs in fish oil could regulate blood pressure and enhance vascular integrity and compliance. Additionally, ω-3-PUFAs have the ability to protect vascular endothelial cells by decreasing oxidative stress, halting atherosclerotic events, and preventing vascular inflammatory and adhesion cascades. Intriguingly, recent studies have demonstrated that ω-3-PUFAs improve the function of vascular endothelium by enhancing the generation and bioavailability of endothelium-derived relaxing factor (nitric oxide) through upregulation and activation of endothelial nitric oxide synthase (eNOS). This certainly opens up a new area of research identifying potential mechanisms influencing fish oil-mediated functional regulatory action on vascular endothelium. We address in this review the potential of fish oil to prevent vascular endothelial dysfunction and associated cardiovascular disorders. Moreover, the mechanisms pertaining to fish oil-mediated eNOS activation and nitric oxide generation in improving endothelial function are delineated. We finally suggest the importance of further studies to determine the dose adjustment of fish oil with an optimal ratio of EPA and DHA for achieving consistent cardiovascular protection.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials as Topic
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / pharmacology
  • Eicosapentaenoic Acid / metabolism
  • Eicosapentaenoic Acid / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Fish Oils / pharmacology
  • Fish Oils / therapeutic use*
  • Humans
  • Hypertriglyceridemia / drug therapy*
  • Hypertriglyceridemia / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxidative Stress / drug effects
  • Up-Regulation


  • Fish Oils
  • Docosahexaenoic Acids
  • Nitric Oxide
  • Eicosapentaenoic Acid
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III