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).

• 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).

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).

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 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.

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 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.

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