Eicosapentaenoic acid

Eicosapentaenoic acid (EPA) is an Omega 3 fatty acid found in fish oil. A precursor to DHA, it is anti-inflammatory and may be neuroprotective.

Immune system
EPA inhibits the production of arachidonic acid (AA) and its related pro-inflammatory prostaglandins by competing for the delta-5-desaturase enzyme that produces AA. The more EPA you have in your diet, the less AA you produce. EPA also competes with phospholipase A2, necessary to release AA from cell membranes, a similar mechanism of action to corticosteroids. The eicosanoids produced from EPA are less active than those produced from AA. A high EPA/AA ratio is anti-inflammatory.

EPA inhibits the expression of pro-inflammatory mediators in microglia, including nitric oxide, prostaglandin E2 and pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in lipopolysaccharide-induced activation. Several studies have found both EPA and DHA inhibit microglia activation.

In culture, EPA inhibits prostaglandin D2, a prostaglandin found in large amounts in the brain and in mast cells.

Nervous system
EPA is found in very low levels in the brain (in contrast to DHA, which is the primary structural Omega 3 in the brain and found in abundance). However, EPA still has important neurological and psychiatric effects.

EPA inhibits Phospholipase A2 (PLA2), an enzyme that breaks down phospholipids, the major component of cell membranes. Increased PLA2 activity has been observed in the cerebrospinal fluid of patients with Alzheimer's and multiple sclerosis.

Some animal studies have found that fish oil increases dopamine, which may be low in CFS patients.

Chronic fatigue syndrome
One study found CFS patients had low EPA/AA and Omega3/Omega 6 (ω3/ω6) ratios.

EPA is a theorized treatment for CFS owing to its immunomodulatory and anti-inflammatory effects. Trial results have been mixed.

Autoimmune disease
A meta-analysis demonstrated significant improvements with fish oil supplementation for rheumatoid arthritis patients. Oral supplementation of EPA and DHA induced prolonged remission of lupus in ten patients.