Eicosapentaenoic acid

Eicosapentaenoic acid

Names
IUPAC name (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid
Identifiers
CAS Number	10417-94-4 Y
ChEBI	CHEBI:28364 Y
ChEMBL	ChEMBL460026 Y
ChemSpider	393682 Y
DrugBank	DB00159 Y
IUPHAR/BPS	3362
Jmol interactive 3D	Image
UNII	AAN7QOV9EA Y
InChI InChI=1S/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15- Y Key: JAZBEHYOTPTENJ-JLNKQSITSA-N Y InChI=1/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15- Key: JAZBEHYOTPTENJ-JLNKQSITBZ
SMILES O=C(O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC
Properties
Chemical formula	C20H30O2
Molar mass	302.451 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Eicosapentaenoic acid (EPA or also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five cis double bonds; the first double bond is located at the third carbon from the omega end.

EPA is a polyunsaturated fatty acid (PUFA) that acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids. Studies of fish oil supplements, which contain EPA, have failed to support claims of preventing heart attacks or strokes.^[1][2][3]

Sources

It is obtained in the human diet by eating oily fish or fish oil, e.g. cod liver, herring, mackerel, salmon, menhaden and sardine, and various types of edible seaweed and phytoplankton. It is also found in human breast milk.

However, fish can either synthesize EPA from fatty acids precursors found in their alimentation^[4] or obtain it from the algae they consume.^[5] It is available to humans from some non-animal sources (e.g. commercially, from microalgae, which are being developed as a commercial source).^[6] EPA is not usually found in higher plants, but it has been reported in trace amounts in purslane.^[7] In 2013, it was reported that a genetically modified form of the plant Camelina produced significant amounts of EPA.^[8][9]

The human body converts alpha-linolenic acid (ALA) to EPA. ALA is itself an essential fatty acid, an appropriate supply of which must be ensured. The efficiency of the conversion of ALA to EPA, however, is much lower than the absorption of EPA from food containing it. Because EPA is also a precursor to docosahexaenoic acid (DHA), ensuring a sufficient level of EPA on a diet containing neither EPA nor DHA is harder both because of the extra metabolic work required to synthesize EPA and because of the use of EPA to metabolize into DHA. Medical conditions like diabetes or certain allergies may significantly limit the human body's capacity for metabolization of EPA from ALA.

Clinical significance

Salmon is a rich source of EPA.

The US National Institute of Health's MedlinePlus lists medical conditions for which EPA (alone or in concert with other ω-3 sources) is known or thought to be an effective treatment.^[10] Most of these involve its ability to lower inflammation.

EPA has been approved by the FDA alone and in combination with other ingredients as an adjunct to diet to reduce triglyceride (TG) levels in patients with very high triglycerides (VHTG).^[11] When used to reduce very high triglycerides, defined as TG ≥ 500 mg/dL, the FDA-approved prescription EPA-only omega-3 fatty acid product was not associated with increases in LDL-C as compared to placebo in a clinical trial.^[12] Prescription and supplement omega-3 fatty acid mixtures that contain docosahexaenoic acid (DHA) may elevate LDL-C.^[13]

EPA has been identified as a potent antioxidant. Antioxidants may play a role by protecting against the toxic effects of free radicals.^[14] EPA has been shown to benefit endothelial function ^[15] and lipid peroxidation in humans,^[16] both of which are associated with atherosclerosis. Due to its potent antioxidant effects, EPA, compared with other TG-lowering agents and DHA, uniquely reduces lipoprotein oxidation in-vitro.^[17][18][19] Further, improvements in endothelial function, represented by changes in nitric oxide (NO) release, alone and in combination with statin, have been observed with EPA, but not DHA or other triglyceride-lowering agents.^[17][20] When tested in vitro in model membrane lipid vesicles, EPA, but not other TG-lowering agents tested in this model, inhibited the formation of cholesterol crystalline domains associated with atherosclerosis.^[19]

Among omega-3 fatty acids, it is thought that EPA in particular may possess some beneficial potential in mental conditions, such as schizophrenia.^[21][22]

Studies have suggested that EPA may be efficacious in treating depression. A 2009 meta-analysis found that people taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms.^[23]

EPA has an inhibitory effect on CYP2C9 and CYP2C19 hepatic enzymes. At a high dose, it may also inhibit the activity of CYP2D6 and CYP3A4, important enzymes involved in drug metabolism.^[24]

In human pharmacokinetic studies, no drug to drug interactions were observed with EPA in combination with omeprazole, rosiglitazone, warfarin, and atorvastatin which are typical substrates of cytochrome P450 enzymes.^{[25][26][27][28]}

Research suggests that EPA improves the response of patients to chemotherapy, possibly by modulating the production of eicosanoid.^[29]

References