Uses of this Supplement
Chronic Obstructive Pulmonary Disease
Crohn's Disease
Diabetes Mellitus
Rheumatoid Arthritis
Ulcerative Colitis
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Aspirin-containing Medications
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
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Look Up > Supplements > Eicosapentaenoic Acid (EPA)
Eicosapentaenoic Acid (EPA)
Dietary Sources
Therapeutic Uses
Dosage Ranges and Duration of Administration
Side Effects/Toxicology
Commercial Preparations


Eicosapentaenoic acid (EPA) is a 20-carbon omega-3 fatty acid that is derived from the desaturation and elongation of alpha-linolenic acid (ALA), an 18-carbon omega-3 essential fatty acid (Mantzioris et al. 1995). Metabolism of EPA generates eicosanoids such as leukotrienes, prostaglandins, and thromboxanes that are involved in a variety of homeostatic functions.

The typical Western diet is high in n-6 fatty acids and low in n-3 fatty acids (Mantzioris et al. 1995). Such a diet appears to be relatively deficient in n-3 fatty acids compared to the diets on which humans evolved (Simopoulos 2000). Cold water fish are the main concentrated sources of dietary EPA. Experimental studies indicate that ingestion of fish oils can raise tissue concentrations of EPA (Mantzioris et al. 1995). Increased intake of EPA has been shown to be beneficial in coronary heart disease, hypertension, and inflammatory disorders such as rheumatoid arthritis (Mantzioris et al. 1995; Simopoulos 1999b).

Dietary Sources
  • Cold water fish: wild salmon (not farm raised), mackerel, sardines, herring (Schmidt 1997)


EPA is a 20-carbon omega-3 fatty acid (20:5n-3 fatty acid).

Therapeutic Uses

Autoimmune Disease: Dietary n-3 fatty acids have been shown to modify the immune response and may be of benefit in inflammatory autoimmune diseases such as rheumatoid arthritis. At least seven double-blind, placebo-controlled trials have been conducted using n-3 fatty acids in patients with rheumatoid arthritis. In all seven studies there were modest but statistically significant benefits observed in treated patients (Robinson et al. 1994). Fish oils have also been shown to improve joint pain in rheumatoid arthritis when used in conjunction with antirheumatic drugs (Simopoulos 1991).

Cardiovascular Health: A substantial amount of scientific data suggests that long chain n-3 fatty acids may prevent the development of atherosclerosis (Angerer and von Schacky 2000; Meydani 2000). According to clinical trials, fish oil may lower serum triglyceride levels and positively alter blood lipid profiles by increasing high-density lipoprotein-2 cholesterol (Bonaa et al. 1992; Foulon et al. 1999; Franceschini et al. 1991; Mori et al. 1992; Sanders and Hinds 1992). Numerous prospective cohort studies suggest that increased intake of fish and shellfish can reduce the risk of sudden cardiac death during cardiac ischemia, particularly in individuals who rarely consume fish (Albert et al. 1998). Fish oil supplementation also reduces hypertension in diabetic and non-diabetic obese, hypertensive, dyslipidemic patients (Yosefy et al. 1999).

Growth and Development: Omega-3 fatty acids are essential for normal growth and development. A group of nutrition experts, under the auspices of the International Society for the Study of Fatty Acids and Lipids (Issfal), have issued recommendations for adequate intakes of n-3 fatty acids in infant formulas and diets (Simopoulos et al. 1999a). According to these recommendations, adequate intakes for infants on formula diets should be less than 0.1% EPA.

Other Conditions: There is evidence to suggest that n-3 fatty acids from fish oils may also benefit patients with chronic obstructive pulmonary disease or renal disease and could be useful for conditions such as ulcerative colitis, Type II diabetes, and Crohn's disease (Simopoulos 1999b).

Dosage Ranges and Duration of Administration

Dietary recommendations: 2 to 3 servings of fatty fish per week, which corresponds to 1.25 g EPA plus DHA per day (Gerster 1998).

Fish oil supplements: 3 to 4 g standardized fish oils per day. This amount corresponds to 2 to 3 servings of fatty fish per week (Gerster 1995).

Side Effects/Toxicology

Side effects observed in clinical trials using fish oil capsules include loose stools, abdominal discomfort, and unpleasant eructation (Robinson et al. 1994). Although it does not appear to pose a clinical concern, fish oil supplements may also cause a slight prolongation of bleeding time (Robinson et al. 1994; Simopoulos 1991).


Some sources say that supplements containing EPA are not recommended for infants or small children because they offset the balance between DHA and EPA during this phase of development (Schmidt 1997). By inference, it would be wise to exercise caution in pregnant women as well.

Consumption of fish oils may increase antioxidant requirements in the body; some recommend that individuals taking fish oil supplements should take extra vitamin E (Meydani 1992). Caution should likely be exercised, though, when using this combination in patients with bleeding disorders as well as in patients on anticoagulant or antiplatelet medications.


In a double-blind, randomized, crossover study, six healthy volunteers were given aspirin (40 mg/day) combined with omega-3 fatty acids (5.3 g) (Iacoviello et al. 1992). The combination lowered the fibrinolytic response to venous occlusion and could be helpful in the treatment of some forms of coronary artery disease.


In a double-blind, randomized, placebo-controlled study, 28 cardiac transplant patients received an immunosuppressive regimen consisting of cyclosporine (6 mg/kg body weight), azathioprine (2 mg/kg/day), and prednisolone (0.2 mg/kg/day) with either omega-3 fatty acids (4 g/day: 46.5% EPA and 37.8% DHA) or placebo (Andreassen et al. 1997). Both treatment groups also received alpha-tocopherol (3.7 mg). Treatment commenced 4 days postoperatively and continued for 6 months, with blood levels of cyclosporine remaining stable for both groups. After 6 months, systolic blood pressure decreased in the omega-3 group and increased in the control group. Diastolic blood pressure increased in both groups; this increase was statistically significant in the control group. An earlier study in 20 cardiac transplant patients receiving omega-3 fatty acids (3 g/day: EPA and DHA) in conjunction with cyclosporine and antihypertensive medications for 12 weeks supports these findings (Ventura et al. 1993). The mechanism of action may be due to decreasing systemic vascular resistance. The combination of omega-3 fatty acids with cyclosporine may show promise as effective hypertension prophylaxis in cardiac transplant patients.

Another placebo-controlled, prospective, double-blind, randomized study involving 26 patients was conducted to evaluate the effects of omega-3 fatty acids on cyclosporine-induced nephrotoxicity (Badalamenti et al. 1995). Liver transplant patients were given omega-3 fatty acids (12 g/day: 18% EPA and 12% DHA) or placebo while on cyclosporine therapy. After 2 months, renal plasma flow increased by 22%, the glomerular filtration rate (GFR) increased by 33%, renal blood flow increased by 17%, and renal vascular resistance decreased by 20% for patients receiving omega-3 fatty acids. No changes were noted in the control group.

Kidney transplant recipients also benefited from supplementation with omega-3 fatty acids (6 g: 30% EPA and 20% DHA) during cyclosporine therapy in a double-blind, placebo-controlled, prospective, randomized clinical trial involving 21 subjects (Homan van der Heide et al. 1990). After 3 months, blood pressure decreased in the omega-3 group, and GFR and renal plasma flow increased by 20.3% and 16.4%, respectively. However, another double-blind, randomized, controlled study with 25 renal transplant patients did not demonstrate any clinically significant benefits derived from one year of treatment with omega-3 fatty acids (6 g: 30% EPA, 20% DHA) (Kooijmans-Coutinho et al. 1996).


A randomized, open study was conducted to evaluate the effects of highly purified EPA (1800 mg/day) in combination with low-dose etretinate (0.3 to 0.5 mg/kg/day) for 12 weeks in patients with chronic, stable psoriasis vulgaris (Danno and Sugie 1998). Patients continued to be treated with a topical corticosteroid that previously had been ineffective. At the end of the study, clinical improvement was noted in 100% of the patients receiving etretinate with EPA as compared to 90% in the patients receiving etretinate monotherapy. The number of patients reporting adverse reactions was similar in both groups.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Omega-3 fatty acids (5 and 10 mL/kg body weight) significantly protected the gastric mucosa against ulcers induced by NSAIDs, reserpine, and necrotizing agents in rats (Al-Harbi et al. 1995).

Commercial Preparations

Commercial products include (Ringer et al 1998)

  • Fish oil capsules that contain EPA plus DHA

Some products may also contain vitamin E to prevent oxidation of the oil in the capsule to maintain freshness through the expiration date. Follow the directions on product labels for both dosage information and storage requirements. Some products may require refrigeration. Do not use products beyond their expiration date.


Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998;279(1):23-28.

Al-Harbi MM, Islam MW, Al-Shabanah OA, Al-Gharably NM. Effect of acute administration of fish oil (omega-3 marine triglyceride) on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats. Food Chem Toxicol. 1995;33(7):555-558.

Andreassen AK, Hartmann A, Offstad J, Geiran O, Kvernebo K, Simonsen S. Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients. J Am Coll Cardiol. 1997;29(6):1324-1331.

Angerer P, von Schacky C. n-3 polyunsaturated fatty acids and the cardiovascular system. Curr Opin Lipidol. 2000;11(1):57-63.

Badalamenti S, Salerno F, Lorenzano E, et al. Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients. Hepatol. 1995;22(6):1695-1701.

Bonaa KH, Bjerve KS, Nordoy A. Docosahexaenoic and eicosapentaenoic acids in plasma phospholipids are divergently associated with high density lipoprotein in humans. Arterioscler Thromb. 1992;12(6):675-681.

Carlson SE. Arachidonic acid status of human infants: influence of gestational age at birth and diets with very long chain n-3 and n-6 fatty acids. J Nutr. 1996;126(4 suppl);1092S-1098S.

Danno K, Sugie N. Combination therapy with low-dose etretinate and eicosapentaenoic acid for psoriasis vulgaris. J Dermatol. 1998;25(11):703-705.

Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336(15):1046-1053.

Foulon T, Richard MJ, Payen N, et al. Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects. Scand J Clin Lab Invest. 1999;59(4):239-248.

Franceschini G, Calabresi L, Maderna P, Galli C, Gianfranceschi G, Sirtori CR. Omega-3 fatty acids selectively raise high-density lipoprotein 2 levels in healthy volunteers. Metab. 1991;40(12):1283-1286.

Ganong WF. Review of Medical Physiology. 13th ed. East Norwalk, Conn: Appleton & Lange; 1987:229-261.

Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res. 1998;68(3);159-173.

Gerster H. The use of n-3 PUFAs (fish oil) in enteral nutrition. Int J Vitam Nutr Res. 1995;65(1):3-20.

Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol. 2000;35(2):265-270.

Haw M, Linnebjerg H, Chavali SR, Forse RA. The effect of dietary polyunsaturated fatty acids (PUFA) on acute rejection and cardiac allograft blood flow in rats. Transplantation. 1995;60(6):570-577.

Homan van der Heide JJ, Bilo HJ, Tegzess AM, Donker AJ. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients. Transplantation. 1990;49(3):523-527.

Iacoviello K, Amore C, De Curtis A, et al. Modulation of fibrinolytic response to venous occlusion in humans by a combination of low-dose aspirin and n-3 polyunsaturated fatty acids. Arterioscler Thromb. 1992;12(10):1191-1197.

Kooijmans-Coutinho MF, Rischen-Vos J, Hermans J, Arndt JW, van der Woude FJ. Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown. J Am Soc Nephrol. 1996;7(3):513-518.

Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312(19):1205-1209.

Mantzioris E, James MJ, Gibson RA, Cleland LG. Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr. 1994;59(6):1304-1309.

Mantzioris E, James MJ, Gibson RA, Cleland LG. Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr. 1995;61(2):320-324.

Meydani M. Omega-3 fatty acids alter soluble markers of endothelial function in coronary heart disease patients. Nutr Rev. 2000;58(2 pt 1):56-59.

Meydani M. Vitamin E requirement in relation to dietary fish oil and oxidative stress in elderly. EXS. 1992;62:411-418.

Mori TA, Vandongen R, Mahanian F, Douglas A. Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation. Metab. 1992;41(10):1059-1067.

Ringer DL, Lombordo R, Wooster AD, eds. Physicians' Guide to Nutriceuticals. Omaha, Neb: Nutritional Data Resources; 1998

Robinson DR, Xu LL, Knoell CT, et al. Alleviation of autoimmune disease by n-3 fatty acids. World Rev Nutr Diet. 1994;76:95-102.

Sanders TA, Hinds A. The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers. Br J Nutr. 1992;68(1):163-173.

Schmidt MA. Smart Fats. Berkeley, Calif: Frog, Ltd; 1997:173-194.

Simopoulos AP. Human requirement for N-3 polyunsaturated fatty acids. Poult Sci. 2000;79(7):961-970.

Simopoulos AP, Leaf A, Salem N Jr. Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids. April 7–9 1999a. International Society for the Study of Fatty Acids and Lipids (Issfal). Accessed at on November 10, 2000.

Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999b;70(3 suppl):560S-569S.

Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54(3):438-463.

Ventura HO, Milani RV, Lavie CJ, et al. Cyclosporine-induced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circ. 1993;88(5 pt 2):II281-II285.

Yosefy C, Viskoper JR, Laszt A, et al. The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 1999;61(2):83-87.

Copyright © 2000 Integrative Medicine Communications

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