Comprehensive Guide to Eicosapentaenoic Acid
(EPA) (Fish Oil) (see also DHA)

Eicosapentaenoic Acid Dr. James Meschino DC, MS, ND
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General Features
Fish oil contains Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). These omega-3 fatty acids occur in fish oil typically as 18 percent EPA, 12 percent DHA, for a total of 30 percent omega-3 composition.
These unique omega-3 fatty acids provide a number of health benefits such as lowering triglycerides, reducing platelet stickiness and providing immediate precursors that provide anti-inflammatory activity.1,2
Supplementation with fish oil has been shown to increase the synthesis of prostaglandins (hormone-like substances) and other eicosanoids that reduce inflammation and decrease platelet coaguability and thrombotic tendencies, while facilitating vasodilation.3,4,5
Various polyunsaturated fats of the omega-6 and omega-3 series provide the precursors for prostaglandin and eicosanoids synthesis. Omega-3 fats from fish oil have been studied extensively and a number of clinical trials reveal the benefit of omega-3 fatty acid supplementation in the prevention and management of various health conditions
Supplementation Studies and Clinical Applications
1. Lower Triglycerides
Fish oil supplementation has consistently been shown to help reduce hypertriglyceridemia by 30-64 percent5 (i.e. salmon oil 30 gms per day). More typically 15 gm of fish oil per day is used to lower triglyceride levels.
2. Decrease Platelet Stickiness
Studies demonstrate that fish oil supplementation reduces platelet coaguability and thrombotic tendencies, via the conversion of EPA to prostaglandin-series 3 end products
3. Blood Pressure
Many studies have revealed that supplementation with either fish oil or flaxseed oil can lower blood pressure in hypertensive subjects
4. Rheumatoid Arthritis
Studies using fish oil supplementation in patients with rheumatoid arthritis demonstrate that it can profoundly reduce morning stiffness, joint tenderness and the synthesis of pro-inflammatory eicosanoids. Over a dozen studies of this nature suggest its superiority in this regard to oils that feature gamma-linolenic acid (i.e. evening primrose oil)
5. Multiple Sclerosis
Dr. Roy Swank, a professor of Neurology, provided evidence that manipulating dietary fats can slow the progression of M.S. In short the Swank Diet encourages less saturated and hydrogenated fats, one teaspoon per day of cod liver oil (containing EPA and DHA), 40-50 gms (3-4 tablespoons) of polyunsaturated vegetable oils, with fish consumption three or more times per week (plus low fat protein foods, vegetables and some nuts).
6. Crohn’s Disease
Fish oil supplementation has been shown to benefit patients with Crohn’s Disease via its effects on promoting the formation of anti-inflammatory eicosanoids.
7. Ulcerative Colitis
Treatment with EPA (3-4 gms per day) was shown to decrease the synthesis of pro-inflammatory leukotrienes and platelet responsiveness in patients with ulcerative colitis in a small study.
8. Raynaud’s Phenomenon
Due to its effects on prostaglandin metabolism, fish oil has helped some people with Raynaud’s Phenomenon in double-blind research.

N.B.: for eczema and asthma, see DHA (fish oil)
Dosage Ranges
For the above conditions mentioned in this section the usual dosage of fish oil is 10-15 gms of EPA plus DHA A lesser, ideal amount for healthy people has not been determined.
Side Effects and Toxicity
Some individuals report gastrointestinal upset and fish-tasting regurgitation.6
DHA and EPA are very non-toxic, but fish oil is easily damaged by oxygen forming undesirable peroxides and other free radicals. It should be consumed with adequate vitamin E to guard against oxidation (100-400 I.U. per day).15 Some patients experience nose bleeds due to the anti-clogging effect of EPA

Contraindications and Drug-Nutrient Interactions
Patients on anti-coagulant therapy must consult with their physicians before supplementing with fish oil. Fish oil can further enhance the anti-clotting behaviour of platelets and potentially increase risk of bleeding disorders.17
Fish oil supplementation may also increase blood cholesterol, thus, certain heart disease patients must exercise caution with use of fish oil supplementation.18
High doses of fish oil can increase insulin resistance in diabetics. The maximum dosage for diabetics should not exceed 2.5 gm fish oils or 900 mg of purified EPA supplementation. This level appears to be safe and may decrease platelet stickiness, which may help diabetics reduce risk of cardiovascular complications
References
1. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.
2. Mate J, Castanos R, Garcia-Samaniego J, Pajares JM. Does dietary fish oil maintain the remission of Crohn’s disease: a case study. Gastroenterology 1991;100:A228[abstract].
3. Lee TH, Hoover RL, Williams JD. Effect of dietary enrichment with eicosapentaenoic and docosahexanoic acids on in vitro neutraphil and monocyte leukotriene generation and neutrophil generation. New Eng J Med 1985,312:1217-24.
4. Strasser T, Fischer S, Weber P. Leukotriene B5 is formed in human neutrophils after dietary supplementation with EPA. Proc Nat Acad Sci 1985;82:1540-3.
5. Kinsella JE, Lokesh B, Stone RA. Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms. Am J Clin Nutr 1990;52:1-28.
6. Murray M. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Publishing; 1996. p. 249-78.
7. Cobiac L, Clifton PM, Abbey M, et al. Lipid, lipoprotein, and hemostatic effects of fish vs fish oil w-3 fatty acids in mildly hyperlipidemic males. Am J Clin Nutr 1991;53:1210-6.
8. Schmidt EB, Dyerberg J. Omega-3 fatty acids: Current status in cardiovascular medicine. Drugs 1994;47:405-24.
9. Appel LJ, Miller ER, Seidler AJ, Whelton PK. Dose supplementation of diet with “fish oil” reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med 1993;153:1429-38.
10. Singer P. Alpha-linolenic acid vs long-chain fatty acids in hypertension and hyperlipidemia. Nutrition 1992;8:133-5.
11. Swank RL. Multiple sclerosis: fat-oil relationship. Nutrition 1991;7:368–76.
12. Swank RL, et al. The Multiple Sclerosis Diet Book. Garden City, NY: Doubleday; 1977.
13. Belluzzi, A, Boschi, S, Brignola, C, Munarini, A, Cariani, G, Miglio F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr 2000;71(Suppl):339S-42S.
14. DiGiacoma RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud’s phenomenon: A double-blind, controlled prospective study. Am J Med 1989;86:158-64.
15. Piche LA, Draper HH, Cole PD. Malondialdehyde excretion by subjects consuming cod liver oil vs a concentrate of n-3 fatty acids. Lipids 1988;23:370-1.
16. Clarke JTR, Cullen-Dean G, Reglink E, et al. Increased incidence of epistaxis in adolescents with familial hypercholesterolemia treated with fish oil. J Pediats 1990;116:139-41.
17. Pederson HS, et al. n-3 fatty acids as a risk factor for hemorrhagic stroke. Lancet 1999;353:812-3.
18. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988;37:1567-73.
19. Axelrod L, Camuso J, Williams E, Kleinman K, Briones E, Schoenfeld D. Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM: a randomized, prospective, double-blind, controlled study. Diabetes Care 1994;17:37-44.