Eicosapentaenoic acid (EPA; 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.

Quick Facts Names, Identifiers ...

Eicosapentaenoic acid

Names
Preferred IUPAC name (5Z,8Z,11Z,14Z,17Z)-Icosa-5,8,11,14,17-pentaenoic acid
Other names (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-eicosapentaenoic acid
Identifiers
CAS Number	10417-94-4 Y
3D model (JSmol)	Interactive image
3DMet	B00962
Beilstein Reference	1714433
ChEBI	CHEBI:28364 Y
ChEMBL	ChEMBL460026 Y
ChemSpider	393682 Y
DrugBank	DB00159 Y
ECHA InfoCard	100.117.069
IUPHAR/BPS	3362
KEGG	C06428
PubChem CID	446284
UNII	AAN7QOV9EA Y
CompTox Dashboard (EPA)	DTXSID9041023
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
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H314
Precautionary statements	P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P405, P501
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

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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. EPA is both a precursor and the hydrolytic breakdown product of eicosapentaenoyl ethanolamide (EPEA: C₂₂H₃₅NO₂; 20:5,n-3).^[1] Although studies of fish oil supplements, which contain both docosahexaenoic acid (DHA) and EPA, have failed to support claims of preventing heart attacks or strokes,^[2][3][4] a recent multi-year study of Vascepa (ethyl eicosapentaenoate, the ethyl ester of the free fatty acid), a prescription drug containing only EPA, was shown to reduce heart attack, stroke, and cardiovascular death by 25% relative to a placebo in those with statin-resistant hypertriglyceridemia.^[5][6]

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

Fish, like most vertebrates, can synthesize very little EPA from dietary alpha-linolenic acid (ALA).^[7] Because of this extremely low conversion rate, fish primarily obtain it from the algae they consume.^[8] It is available to humans from some non-animal sources (e.g., commercially, from Yarrowia lipolytica,^[9] and from microalgae such as Nannochloropsis oculata, Monodus subterraneus, Chlorella minutissima and Phaeodactylum tricornutum,^[10][11] which are being developed as a commercial source).^[12] EPA is not usually found in higher plants, but it has been reported in trace amounts in purslane.^[13] In 2013, it was reported that a genetically modified form of the plant camelina produced significant amounts of EPA.^[14][15]

The human body converts a portion of absorbed alpha-linolenic acid (ALA) to EPA. ALA is itself an essential fatty acid, and humans need an appropriate supply of it. 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.

Commercially available dietary supplements are most often derived from fish oil and are typically delivered in the triglyceride, ethyl ester, or phospholipid form of EPA. There is debate among supplement manufacturers about the relative advantages and disadvantages of the different forms. One form found naturally in algae, the polar lipid form, has been shown to have improved bioavailability over the ethyl ester or triglyceride form.^[16] Similarly, DHA or EPA in the lysophosphatidylcholine (LPC) form was found to be more efficient than triglyceride and phosphatidylcholines (PC) in a 2020 study.^[17]

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.^[21] Most of these involve its ability to lower inflammation.

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega-3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater than 500 mg/dL).

Dietary supplements containing EPA and DHA lower triglycerides in a dose dependent manner; however, DHA appears to raise low-density lipoprotein (the variant which drives atherosclerosis, sometimes inaccurately called "bad cholesterol") and LDL-C values (a measurement/estimate of the cholesterol mass within LDL-particles), while EPA does not. This effect has been seen in several meta-analyses that combined hundreds of individual clinical trials in which both EPA and DHA were part of a high dose omega-3 supplement, but it is when EPA and DHA are given separately that the difference can be seen clearly.^[22][23] For example, in a study by Schaefer and colleagues of Tufts Medical School, patients were given either 600 mg/day DHA alone, 600 or 1800 mg/day EPA alone, or placebo for six weeks. The DHA group showed a significant 20% drop in triglycerides and an 18% increase in LDL-C, but in the EPA groups modest drops in triglyceride were not considered statistically significant and no changes in LDL-C levels were found with either dose.^[24]

Ordinary consumers commonly obtain EPA and DHA from foods such as fatty fish,^{[lower-alpha 1]} fish oil dietary supplements,^{[lower-alpha 2]} and less commonly from algae oil supplements^{[lower-alpha 3]} in which the omega-3 doses are lower than those in clinical experiments. A Cooper Center Longitudinal Study that followed 9253 healthy men and women over 10 years revealed that those who took fish oil supplements did not see raised LDL-C levels.^[25] In fact, there was a very slight decrease of LDL-C which was statistically significant but too small to be of any clinical significance. These individuals took fish oil supplements of their own choosing, and it should be recognized that the amounts and ratios of EPA and DHA vary according to the source of fish oil.

Omega-3 fatty acids, particularly EPA, have been studied for their effect on autistic spectrum disorder (ASD). Some have theorized that, since omega-3 fatty acid levels may be low in children with autism, supplementation might lead to an improvement in symptoms. While some uncontrolled studies have reported improvements, well-controlled studies have shown no statistically significant improvement in symptoms as a result of high-dose omega-3 supplementation.^[26][27]

In addition, studies have shown that omega-3 fatty acids may be useful for treating depression.^[28][29]

EPA and DHA ethyl esters (all forms) may be absorbed less well, thus work less well, when taken on an empty stomach or with a low-fat meal.^[30]