Eicosapentaenoic Acid (EPA)

Overview

Eicosapentaenoic acid (EPA) is a member of the omega-3 family of fatty acids. Although EPA can be consumed directly by eating certain kinds of fish, it is also produced in the body from the conversion of alpha linolenic acid (ALA), also known as omega-3. The metabolic processes that convert omega-3 to EPA is accomplished by desaturase and elongase enzymes. Desaturase enzymes produce additional double bonds, while elongase enzymes add carbon atoms to make a longer fatty acid chain. The parent or precursor omega-3 molecule, alpha linolenic acid (ALA), is a long-chain fatty acid that contains 18 carbon atoms with three double bonds. Under the influence of the desaturase and elongase enzymes, omega-3 is converted to eicosapentaenoic acid, which is a fatty acid that is 20 carbons long and contains five double bonds. EPA is the precursor compound for the conversion to a group of chemicals called the series 3 prostaglandins (PGE3), which provide anti-inflammatory activity, (1) enhance the immune system, thin the blood, and lower blood pressure.

Dosage Info

Dosage Range

170mg to 3.6 grams of EPA daily, or 3 to 12 grams of fish oil concentrate daily.

Most Common Dosage

1-2 grams of EPA daily.

Dosage Forms

Capsules and tablets.

Adult RDI

None established

Adult ODA

None established

RDA

  • : None established

Interactions and Depletions

Interactions

Active Forms

Eicosapentaenoic acid

Absorption

EPA is absorbed from the intestinal tract, but since it is a fat, absorption is dependent on the amount of fat being consumed at that particular meal. One study reported that the absorption of EPA and DHA fish oils was increased three-fold when consumed with a high-fat meal. (2)

Toxicities & Precautions

General

Individuals who ingest supplemental EPA are advised to take additional antioxidants, especially vitamin E, to protect against free radical oxidation in the body. (3)

Side Effects

Some people who take supplemental EPA in the form of fish oil complain of gastrointestinal burping and belching, which causes a “fishy” odor.

Functions in the Body

Series 3 prostaglandins

EPA is the precursor to the series 3 prostaglandins (PGE3), which provide anti-inflammatory activity, enhance the immune system, and reduce platelet stickiness and blood pressure. (4)

Cellular membranes

Increased amounts of EPA in cellular membranes will help reduce the amount of pro-inflammatory omega-6 fat known as arachidonic acid in cellular membranes. (5)

Leukotriene B5

In leukocytes, through the lipoxygenase pathway, EPA metabolism produces leukotriene B5, which provides anti-inflammatory activity and reduces platelet adhesion. (6)

Prostacyclin I3

In endothelial cells, through the cyclooxygenase pathway, EPA metabolism produces prostacyclin I3, which relaxes blood vessels and reduces platelet aggregation. (7)

Lowering triglycerides

EPA plays a major role in lowering triglycerides in the body. (8) , (9)

Clinical Applications

Elevated Triglycerides

Studies indicate that EPA (not DHA) is the omega-3 fatty acid that is primarily responsible for lowering elevated levels in humans. (10)

Angina Pectoris

Studies indicate that a fish oil concentrate rich in EPA given to heart disease patients resulted in decreased platelet aggregation along with a significant reduction in angina attacks and the use of nitroglycerin medications. (11)

Cardiac Arrhythmias

Studies reportedly reveal that EPA is able to prevent and correct potentially fatal cardiac arrhythmias and stabilize the electrophysiology of the heart. (12)

Crohn's Disease

Therapy with longer-chain omega-3 fatty acids, EPA and DHA, decrease the inflammatory activity in patients with Crohn’s disease. (13) , (14)

Rheumatoid Arthritis

Patients consuming fish oils (EPA and DHA) reportedly have a substantial reduction in pro-inflammatory eicosanoids prostaglandin E(2) and leukotriene B(4), and up to a 90 percent reduction in pro-inflammatory cytokines. (15) In another trial, patients had significant reductions in tender points and swollen joints with high dose consumption of fish oils (54 mg/kg EPA and 36 mg/kg DHA), providing better improvement than low dose consumption (27 mg/kg and 18 mg/kg). In this 24-week study, patients on low-dose fish oils obtained significant improvement in eight of 45 clinical measurements, while those on high-dose fish oils gained significant improvement in 21 of 45 categories. (16)

Lupus

Studies indicate that therapy with eicosapentaenoic acid, usually in combination with DHA, provides substantial benefit to patients with lupus. The results of one study reported that oral supplementation of EPA and DHA induced prolonged remission of systemic lupus erythematosus (SLE) in 10 consecutive patients without any side effects. (17)

Bipolar disorder

Evidence suggests that long-chain omega-3 fatty acids contained in fish oils (EPA and DHA) exhibit mood-stabilizing properties in patients with bipolar disorder, which is also known as manic depressive illness. EPA and DHA seem to inhibit neuronal signal transduction pathways in a manner similar to lithium carbonate and valproate, which are medications frequently used to treat this disorder. In a four-month, double-blind, placebo-controlled trial, patients treated with the omega-3 fish oils exhibited a significantly longer period of remission, plus they scored better than the placebo group on virtually every outcome measure that was studied. (18) Researchers found that levels of EPA were significantly lower in bipolar mood disorder patients than in the control group and that supplementation of antioxidants and essential fatty acids may improve the patients’ symptoms. (19)

Asthma

Children who have a higher consumption of oily fish in their diets, which provide EPA and DHA, have significantly reduced incidences of asthma. This is potentially due to the fatty acids reducing the production of pro-inflammatory leukotrienes. (20)

Cancer

In an animal model, the addition of DHA/EPA to the diet resulted in a 35 to 46% reduction in tumor growth. Also, in cell culture studies, DHA resulted in a 46% decrease in cancer cell growth. (21)

Cardiovascular Disease

A study assessed the effect of omega-3 fatty acids on systemic arterial compliance (SAC). SAC is a measure of arterial elasticity and may serve as a marker for cardiovascular disease and related events. In this placebo controlled, randomized, double-blind trial, 38 individuals with dyslipidemias were randomly assigned to one of three groups: 3 g eicosapentaenoic acid (EPA) per day (n = 12), 3 g docosahexaenoic acid (DHA) per day (n = 12), or placebo (n = 14). Arterial functions, lipids and fatty acids were all measured prior to and following the treatment interventions. Compared to placebo the omega-3 fatty acids significantly increased the SAC. EPA increased SAC 36% and DHA increased SAC 27%. In addition, the omega-3 fatty acids significantly lowered the total and VLDL triacylgylcerol levels. (22)

Diabetes

EPA in combination with DHA improves insulin sensitivity in non-insulin dependent diabetes. (23) One study revealed that the membrane phospholipids of people with both type 1 and type 2 diabetes have significantly reduced levels of EPA. (24) EPA given to type 2 diabetics reportedly resulted in an increased production of prostacyclin I3, suggesting that EPA may help prevent the complications associated with diabetes, such as microangiopathy and occlusive vascular disease, as well as lower triglycerides, blood viscosity, and decreased platelet reactivity. (25)

Hypertension

EPA, in combination with DHA, provides a moderate decrease in both diastolic and systolic blood pressure in individuals with moderate hypertension. (26)

Psoriasis

In a cross-over trial, patients eating oily fish for a six-week period, which resulted in a rise in plasma eicosapentaenoic acid, exhibited modest clinical improvements in psoriasis compared to patients eating white fish, which did not alter EPA levels. (27) Modest improvement was also observed in a one-year trial where patients received only EPA, with a corresponding reduction in inflammatory leukotriene B4 (LTB4) and an increase in the formation of anti-inflammatory leukotriene B5 (LTB5). (28)

Ulcerative Colitis

Studies report that providing therapeutic doses of fish oils (EPA and DHA) to patients with ulcerative colitis results in suppression of immune reactivity and concurrent reduction in disease activity. (29) , (30)

Schizophrenia

The results of two double-blind, placebo-controlled trials indicate that eicosapentaenoic acid (EPA) provided substantial therapeutic benefits for patients with schizophrenia when taken in conjunction with antipsychotic medications or as a sole therapy. The researchers concluded that EPA may represent a new treatment approach for schizophrenia. (31) Researchers found that patients with schizophrenia had significantly lower levels of EPA and that supplementation may be of benefit to the patients. (32)

Eczema

After 12 weeks, patients consuming 1.8 grams of EPA daily experienced reduced scaling, itching, and overall improved skin lesions compared to placebo controls. (33)

Symptoms and Causes of Deficiency

A deficiency of EPA has become increasingly common for the following reasons:

    Reduced consumption of cold water fish, which is the primary dietary source of EPA. Low-fat diets reduce consumption of EPA and other important fatty acids. Omega-3 (alpha linolenic acid), the dietary precursor to EPA, is typically removed from food to extend product shelf life. In the last half century, there has been a significant increase in the use of processed oils from the omega-6 family such as corn, sunflower, and safflower oils, which compete with and suppress the body’s ability to convert omega-3 to EPA. Consumption of large quantities of trans fatty acids from foods containing partially hydrogenated fats and oils inhibits the enzyme delta-6-desaturase, which is responsible for the conversion of omega-3 to EPA and DHA and also omega-6 to its longer chain fatty acids. (34) The following nutrients are required for proper function of delta-6 desaturase enzyme activity, which converts omega-3 to EPA and DHA. They are niacin, pyridoxine, ascorbic acid, and zinc. Thus, a deficiency of any of these nutrients could impair the biosynthesis of EPA and DHA. (35)

    Some of the major symptoms of a deficiency of EPA include the following: growth retardation in infants; weakness; impaired vision and learning ability; behavioral changes; dry skin; edema; increased inflammation; sticky platelets; elevated blood pressure; elevated triglycerides; altered metabolism; and weakened immune system.

Dietary Sources

The richest dietary sources of EPA are the oils from cold water fish such as salmon, mackerel, herring, sardines, and other marine animals.

References

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