Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with 20 carbons and 5 double bonds (20:5n3).
EPA can either be made from the downstream metabolism of ALA or it can be obtained in the diet. Food sources include oily fish such as salmon, mackerel, cod, and sardines. In addition to diet and ALA desaturation, EPA is also available as a fish oil supplement. The desaturation of ALA to EPA is not a very efficient process, therefore dietary intake or supplementation is important.
As a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids, EPA carries special importance in the inflammatory cascade. EPA can also lower plasma triglyceride levels without raising low-density lipoprotein cholesterol levels. Some studies suggest that in cardiovascular disease, EPA may decrease plaque vulnerability, prevent progression, and decrease macrophage accumulation. It is also vasodilatory which can lower blood pressure.
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- Nelson JR, Wani O, May HT, Budoff M. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques. Vascular pharmacology. 2017;91:1-9.
- Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. The Journal of clinical psychiatry. 2011;72(12):1577-1584.
- Titova OE, Sjögren P, Brooks SJ, et al. Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly. AGE. 2013;35(4):1495-1505.
- Hirahashi J, Kawahata K, Arita M, et al. Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis. Scientific Reports. 2014;4(1):6406.
- Robinson DR, Xu L-L, Tateno S, Guo M, Colvin RB. Suppression of autoimmune disease by dietary n-3 fatty acids. Journal of lipid research. 1993;34(8):1435-1444.
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- Tajuddin N, Shaikh A, Hassan A. Prescription omega-3 fatty acid products: considerations for patients with diabetes mellitus. Diabetes Metab Syndr Obes. 2016;9:109-118.
- Ashfaq W, Rehman K, Siddique MI, Khan Q-A-A. Eicosapentaenoic Acid and Docosahexaenoic Acid from Fish Oil and Their Role in Cancer Research. Food Reviews International. 2020;36(8):795-814.
- Begtrup KM, Krag AE, Hvas A-M. No impact of fish oil supplements on bleeding risk: a systematic review. Dan Med J. 2017;64(5):A5366.
- Akintoye E, Sethi P, Harris WS, et al. Fish oil and perioperative bleeding: insights from the OPERA randomized trial. Circulation: Cardiovascular Quality and Outcomes. 2018;11(11):e004584.
- Jeansen S, Witkamp RF, Garthoff JA, van Helvoort A, Calder PC. Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition. Clinical Nutrition. 2018;37(3):948-957.
Elevations in EPA can be due to high dietary intake of EPA-containing foods from supplementation with fish oil. Lack of vitamin and mineral cofactors, or SNPs in the elongase enzyme, may also contribute to elevations. It should also be noted that there is competition for the elongase and desaturase enzymes between the omega-3 and omega-6 fatty acids which may affect levels of fatty acid metabolites.
High levels of EPA and its downstream metabolite DHA have been used in treatment for many clinical conditions. Studies show benefit in cardiovascular disease, depression, cognitive decline, autoimmune diseases, skin diseases, inflammation, cancer, and metabolic syndrome. Because of EPA’s anti-platelet effects, oversupplementation was once thought to increase bleeding risk, especially if taken with other anticoagulants. However, new literature finds no increased risk of bleeding in patients taking fish oil supplementation while undergoing surgery and invasive procedures. In fact, some literature demonstrates a reduced need for blood transfusion in these patients.
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