Eicosapentaenoic acid: Difference between revisions

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 ;
3D model (JSmol)	Interactive image;
3DMet	B00962;
Beilstein Reference	1714433
ChEBI	CHEBI:28364 ;
ChEMBL	ChEMBL460026 ;
ChemSpider	393682 ;
DrugBank	DB00159 ;
ECHA InfoCard	100.117.069
IUPHAR/BPS	3362;
KEGG	C06428;
PubChem CID	446284;
UNII	AAN7QOV9EA ;
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- Key: JAZBEHYOTPTENJ-JLNKQSITSA-N ; 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). verify (what is ?) Infobox references

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Latest revision as of 13:05, 7 May 2024

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.

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]

Sources[edit]

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.

Forms[edit]

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]

Base	EPA
Ethyl ester	EPA ethyl ester
Lysophosphatidylcholine (LPC, or lysoPC)	LPC-EPA, or lysoPC-EPA
Phosphatidylcholine (PC)	EPA-PC
Phospholipid (PL)	EPA-PL
Triglyceride (TG) or triacylglycerol (TAG)	EPA-TG, or EPA-TAG
Re-esterified triglyceride (rTG), or re-esterified triacylglycerol (rTAG)	EPA rTG, or r-TAG

Biosynthesis[edit]

Aerobic eukaryote pathway[edit]

Aerobic eukaryotes, specifically microalgae, mosses, fungi, and most animals (including humans), perform biosynthesis of EPA usually occurs as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase enzymes. This pathway, originally identified in Thraustochytrium, applies to these groups:^[18]

a desaturation at the sixth carbon of alpha-linolenic acid by a Δ6 desaturase to produce stearidonic acid (SDA, 18:4 ω-3),
elongation of the stearidonic acid by a Δ6 elongase to produce eicosatetraenoic acid (ETA, 20:4 ω-3),
desaturation at the fifth carbon of eicosatetraenoic acid by a Δ5 desaturase to produce eicosapentaenoic acid (EPA, 20:5 ω-3),

Polyketide synthase pathway[edit]

Marine bacteria and the microalgae Schizochytrium use an anerobic polyketide synthase (PKS) pathway to synthesize DHA.^[18] The PKS pathway includes six enzymes namely, 3-ketoacyl synthase (KS), 2 ketoacyl-ACP-reductase (KR), dehydrase (DH), enoyl reductase (ER), dehydratase/2-trans 3-cos isomerase (DH/2,3I), dehydratase/2-trans, and 2-cis isomerase (DH/2,2I). The biosynthesis of EPA varies in marine species, but most of the marine species' ability to convert C18 PUFA to LC-PUFA is dependent on the fatty acyl desaturase and elongase enzymes. The molecule basis of the enzymes will dictate where the double bond is formed on the resulting molecule.^[19]

The proposed polyketide synthesis pathway of EPA in Shewanella (a marine bacterium) is a repetitive reaction of reduction, dehydration, and condensation that uses acetyl-CoA and malonyl-CoA as building blocks. The mechanism of α-linolenic acid to EPA involves the condensation of malonyl-CoA to the pre-existing α-linolenic acid by KS. The resulting structure is converted by NADPH dependent reductase, KR, to form an intermediate that is dehydrated by the DH enzyme. The final step is the NADPH-dependent reduction of a double bond in trans-2-enoyl-ACP via ER enzyme activity. The process is repeated to form EPA.^[20]

Clinical significance[edit]

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,^[a] fish oil dietary supplements,^[b] and less commonly from algae oil supplements^[c] 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]

Notes[edit]

^ Cooked salmon contain 500–1,500 mg DHA and 300–1,000 mg EPA per 100 grams of fish. See page: Salmon as food.
^ Omega-3 dietary oil supplements have no standard doses and generally salmon oil has more DHA than EPA while other white fishes have more EPA than DHA. One producer, Trident Food's Pure Alaska, for example reports per serving DHA 220 mg and EPA 180 mg for their salmon oil (total omega-3 = 600 mg), but DHA 144 mg and EPA 356 mg for pollock fish oil (total omega-3 = 530 mg). Equivalent products from another producer, Fish Oils, Puritan's Pride, reports DHA 180 mg and EPA 150 mg for their salmon oil product (total omega-3 = 420 mg), but DHA 204 mg and EPA 318 mg for fish oil derived from anchovy, sardine, and mackerel (total omega-3 = 600 mg). For information and comparison purposes only, no endorsements are implied.
^ Many plant sources of omega-3s are rich in ALA but completely lack EPA and DHA. The exception is algae derived oils. Because there are more commercially-grown algae sources of DHA than EPA, algae omega-3 supplements typically contain more DHA than EPA. For example, Nordic Naturals reports per serving DHA 390 mg and EPA 195 mg (total omega-3 = 715 mg), Calgee reports DHA 300 mg and EPA 150 mg (total omega-3 = 550 mg) and so on, but iwi reports EPA 250 mg (total omega-3 = 254 mg). For information and comparison purposes only, no endorsements are implied.

References[edit]

^ Lucanic M, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS (May 2011). "N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans". Nature. 473 (7346): 226–9. Bibcode:2011Natur.473..226L. doi:10.1038/nature10007. PMC 3093655. PMID 21562563.
^ Zimmer C (September 17, 2015). "Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story". The New York Times. Archived from the original on January 9, 2019. Retrieved October 11, 2015.
^ O'Connor A (March 30, 2015). "Fish Oil Claims Not Supported by Research". The New York Times. Archived from the original on May 28, 2018. Retrieved October 11, 2015.
^ Grey A, Bolland M (March 2014). "Clinical trial evidence and use of fish oil supplements". JAMA Internal Medicine. 174 (3): 460–2. doi:10.1001/jamainternmed.2013.12765. PMID 24352849. Archived from the original on 2016-06-08. Retrieved 2015-10-12.
^ Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM (January 3, 2019). "Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia". New England Journal of Medicine. 380 (1): 11–22. doi:10.1056/NEJMoa1812792. PMID 30415628.
^ "Vascepa® (icosapent ethyl) 26% Reduction in Key Secondary Composite Endpoint of Cardiovascular Death, Heart Attacks and Stroke Demonstrated in REDUCE-IT™". November 10, 2018. Archived from the original on May 23, 2019. Retrieved January 21, 2019.
^ Committee on the Nutrient Requirements of Fish and Shrimp; National Research Council (2011). Nutrient requirements of fish and shrimp. Washington, DC: The National Academies Press. ISBN 978-0-309-16338-5.
^ Bishop-Weston Y. "Plant based sources of vegan & vegetarian Docosahexaenoic acid – DHA and Eicosapentaenoic acid EPA & Essential Fats". Archived from the original on 2013-05-22. Retrieved 2008-08-05.
^ Xie, Dongming; Jackson, Ethel N.; Zhu, Quinn (February 2015). "Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production". Applied Microbiology and Biotechnology. 99 (4): 1599–1610. doi:10.1007/s00253-014-6318-y. ISSN 0175-7598. PMC 4322222. PMID 25567511.
^ Vazhappilly R, Chen F (1998). "Eicosapentaenoic acid and docosahexaenoic acid production potential of microalgae and their heterotrophic growth". Journal of the American Oil Chemists' Society. 75 (3): 393–397. doi:10.1007/s11746-998-0057-0. S2CID 46917269.
^ Ratha SK, Prasanna R (February 2012). "Bioprospecting microalgae as potential sources of "Green Energy"—challenges and perspectives". Applied Biochemistry and Microbiology. 48 (2): 109–125. doi:10.1134/S000368381202010X. PMID 22586907. S2CID 18430041.
^ Halliday J (12 January 2007). "Water 4 to introduce algae DHA/EPA as food ingredient". Archived from the original on 2007-01-16. Retrieved 2007-02-09.
^ Simopoulos AP (2002). "Omega-3 fatty acids in wild plants, nuts and seeds" (PDF). Asia Pacific Journal of Clinical Nutrition. 11 (Suppl 2): S163–73. doi:10.1046/j.1440-6047.11.s.6.5.x. Archived from the original (PDF) on 2008-12-17.
^ Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O (January 2014). "Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop". The Plant Journal. 77 (2): 198–208. doi:10.1111/tpj.12378. PMC 4253037. PMID 24308505.
^ Coghlan A (4 January 2014). "Designed plant oozes vital fish oils". New Scientist. 221 (2950): 12. doi:10.1016/s0262-4079(14)60016-6. Archived from the original on 1 June 2015. Retrieved 26 August 2017.
^ Kagan, M. L.; West, A. L.; Zante, C.; Calder, P. C. (2013). "Acute appearance of fatty acids in human plasma--a comparative study between polar-lipid rich oil from the microalgae Nannochloropsis oculata and krill oil in healthy young males". Lipids in Health and Disease. 12: 102. doi:10.1186/1476-511X-12-102. PMC 3718725. PMID 23855409.
^ Sugasini, D; Yalagala, PCR; Goggin, A; Tai, LM; Subbaiah, PV (December 2019). "Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol". The Journal of Nutritional Biochemistry. 74: 108231. doi:10.1016/j.jnutbio.2019.108231. PMC 6885117. PMID 31665653.
^ ^a ^b Qiu, Xiao (2003-02-01). "Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways". Prostaglandins, Leukotrienes and Essential Fatty Acids. 68 (2): 181–186. doi:10.1016/S0952-3278(02)00268-5. ISSN 0952-3278. PMID 12538082.
^ Monroig, Óscar; Tocher, Douglas; Navarro, Juan (2013-10-21). "Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms". Marine Drugs. 11 (10): 3998–4018. doi:10.3390/md11103998. PMC 3826146. PMID 24152561.
^ Moi, Ibrahim Musa; Leow, Adam Thean Chor; Ali, Mohd Shukuri Mohamad; Rahman, Raja Noor Zaliha Raja Abd.; Salleh, Abu Bakar; Sabri, Suriana (July 2018). "Polyunsaturated fatty acids in marine bacteria and strategies to enhance their production". Applied Microbiology and Biotechnology. 102 (14): 5811–5826. doi:10.1007/s00253-018-9063-9. PMID 29749565. S2CID 13680225.
^ NIH Medline Plus. "MedlinePlus Herbs and Supplements: Omega-3 fatty acids, fish oil, alpha-linolenic acid". Archived from the original on February 8, 2006. Retrieved February 14, 2006.
^ AbuMweis, S; Jew, S; Tayyem, R; Agraib, L (February 2018). "Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials". Journal of Human Nutrition and Dietetics. 31 (1): 67–84. doi:10.1111/jhn.12493. PMID 28675488. S2CID 8793334.
^ Chen, H; Deng, G; Zhou, Q; Chu, X; Su, M; Wei, Y; Li, L; Zhang, Z (26 March 2020). "Effects of eicosapentaenoic acid and docosahexaenoic acid versus α-linolenic acid supplementation on cardiometabolic risk factors: a meta-analysis of randomized controlled trials". Food & Function. 11 (3): 1919–1932. doi:10.1039/c9fo03052b. PMID 32175534. S2CID 212730542.
^ Asztalos, IB; Gleason, JA; Sever, S; Gedik, R; Asztalos, BF; Horvath, KV; Dansinger, ML; Lamon-Fava, S; Schaefer, EJ (November 2016). "Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial". Metabolism: Clinical and Experimental. 65 (11): 1636–1645. doi:10.1016/j.metabol.2016.07.010. PMID 27733252.
^ Harris, WS; Leonard, D; Radford, NB; Barlow, CE; Steele, MR; Farrell, SW; Pavlovic, A; Willis, BL; DeFina, LF (January 2021). "Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study". Journal of Clinical Lipidology. 15 (1): 212–217. doi:10.1016/j.jacl.2020.11.011. PMID 33339757. S2CID 229325648.
^ Bent S, Bertoglio K, Hendren RL (August 2009). "Omega-3 fatty acids for autistic spectrum disorder: a systematic review". Journal of Autism and Developmental Disorders. 39 (8): 1145–54. doi:10.1007/s10803-009-0724-5. PMC 2710498. PMID 19333748.
^ Mankad D, Dupuis A, Smile S, Roberts W, Brian J, Lui T, Genore L, Zaghloul D, Iaboni A, Marcon PM, Anagnostou E (2015-03-21). "A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism". Molecular Autism. 6: 18. doi:10.1186/s13229-015-0010-7. PMC 4367852. PMID 25798215.
^ Freeman, Marlene P.; Hibbeln, Joseph R.; Wisner, Katherine L.; Davis, John M.; Mischoulon, David; Peet, Malcolm; Keck, Paul E.; Marangell, Lauren B.; Richardson, Alexandra J.; Lake, James; Stoll, Andrew L. (December 2006). "Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry". The Journal of Clinical Psychiatry. 67 (12): 1954–1967. doi:10.4088/jcp.v67n1217. ISSN 1555-2101. PMID 17194275. Archived from the original on 2020-09-20. Retrieved 2022-10-13.
^ Ilardi, Stephen (28 April 2015). "Therapeutic Lifestyle Change. A new treatment for depression". Therapeutic Lifestyle Change (TLC). Archived from the original on 9 November 2019. Retrieved 9 November 2019. We were never designed for the sedentary, indoor, sleep-deprived, socially-isolated, fast-food-laden, frenetic pace of modern life.
^ Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA (2015). "National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2". Journal of Clinical Lipidology. 9 (6 Suppl): S1–122.e1. doi:10.1016/j.jacl.2015.09.002. PMID 26699442.

External links[edit]

EPA bound to proteins in the PDB
Eicosapentaenoyl Ethanolamide; Anandamide (20:5, n-3); EPEA. - PubChem

[25] Cooked salmon contain 500–1,500 mg DHA and 300–1,000 mg EPA per 100 grams of fish. See page: Salmon as food.

[26] Omega-3 dietary oil supplements have no standard doses and generally salmon oil has more DHA than EPA while other white fishes have more EPA than DHA. One producer, Trident Food's Pure Alaska, for example reports per serving DHA 220 mg and EPA 180 mg for their salmon oil (total omega-3 = 600 mg), but DHA 144 mg and EPA 356 mg for pollock fish oil (total omega-3 = 530 mg). Equivalent products from another producer, Fish Oils, Puritan's Pride, reports DHA 180 mg and EPA 150 mg for their salmon oil product (total omega-3 = 420 mg), but DHA 204 mg and EPA 318 mg for fish oil derived from anchovy, sardine, and mackerel (total omega-3 = 600 mg). For information and comparison purposes only, no endorsements are implied.

[27] Many plant sources of omega-3s are rich in ALA but completely lack EPA and DHA. The exception is algae derived oils. Because there are more commercially-grown algae sources of DHA than EPA, algae omega-3 supplements typically contain more DHA than EPA. For example, Nordic Naturals reports per serving DHA 390 mg and EPA 195 mg (total omega-3 = 715 mg), Calgee reports DHA 300 mg and EPA 150 mg (total omega-3 = 550 mg) and so on, but iwi reports EPA 250 mg (total omega-3 = 254 mg). For information and comparison purposes only, no endorsements are implied.

[1] Lucanic M, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS (May 2011). "N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans". Nature. 473 (7346): 226–9. Bibcode:2011Natur.473..226L. doi:10.1038/nature10007. PMC 3093655. PMID 21562563.

[NYT-20150917-cz-2] Zimmer C (September 17, 2015). "Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story". The New York Times. Archived from the original on January 9, 2019. Retrieved October 11, 2015.

[NYT-20150330-3] O'Connor A (March 30, 2015). "Fish Oil Claims Not Supported by Research". The New York Times. Archived from the original on May 28, 2018. Retrieved October 11, 2015.

[JAMA-201403-4] Grey A, Bolland M (March 2014). "Clinical trial evidence and use of fish oil supplements". JAMA Internal Medicine. 174 (3): 460–2. doi:10.1001/jamainternmed.2013.12765. PMID 24352849. Archived from the original on 2016-06-08. Retrieved 2015-10-12.

[5] Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM (January 3, 2019). "Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia". New England Journal of Medicine. 380 (1): 11–22. doi:10.1056/NEJMoa1812792. PMID 30415628.

[REDUCE-IT-6] "Vascepa® (icosapent ethyl) 26% Reduction in Key Secondary Composite Endpoint of Cardiovascular Death, Heart Attacks and Stroke Demonstrated in REDUCE-IT™". November 10, 2018. Archived from the original on May 23, 2019. Retrieved January 21, 2019.

[7] Committee on the Nutrient Requirements of Fish and Shrimp; National Research Council (2011). Nutrient requirements of fish and shrimp. Washington, DC: The National Academies Press. ISBN 978-0-309-16338-5.

[vegan-8] Bishop-Weston Y. "Plant based sources of vegan & vegetarian Docosahexaenoic acid – DHA and Eicosapentaenoic acid EPA & Essential Fats". Archived from the original on 2013-05-22. Retrieved 2008-08-05.

[9] Xie, Dongming; Jackson, Ethel N.; Zhu, Quinn (February 2015). "Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production". Applied Microbiology and Biotechnology. 99 (4): 1599–1610. doi:10.1007/s00253-014-6318-y. ISSN 0175-7598. PMC 4322222. PMID 25567511.

[10] Vazhappilly R, Chen F (1998). "Eicosapentaenoic acid and docosahexaenoic acid production potential of microalgae and their heterotrophic growth". Journal of the American Oil Chemists' Society. 75 (3): 393–397. doi:10.1007/s11746-998-0057-0. S2CID 46917269.

[pmid22586907-11] Ratha SK, Prasanna R (February 2012). "Bioprospecting microalgae as potential sources of "Green Energy"—challenges and perspectives". Applied Biochemistry and Microbiology. 48 (2): 109–125. doi:10.1134/S000368381202010X. PMID 22586907. S2CID 18430041.

[water4-12] Halliday J (12 January 2007). "Water 4 to introduce algae DHA/EPA as food ingredient". Archived from the original on 2007-01-16. Retrieved 2007-02-09.

[13] Simopoulos AP (2002). "Omega-3 fatty acids in wild plants, nuts and seeds" (PDF). Asia Pacific Journal of Clinical Nutrition. 11 (Suppl 2): S163–73. doi:10.1046/j.1440-6047.11.s.6.5.x. Archived from the original (PDF) on 2008-12-17.

[14] Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O (January 2014). "Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop". The Plant Journal. 77 (2): 198–208. doi:10.1111/tpj.12378. PMC 4253037. PMID 24308505.

[15] Coghlan A (4 January 2014). "Designed plant oozes vital fish oils". New Scientist. 221 (2950): 12. doi:10.1016/s0262-4079(14)60016-6. Archived from the original on 1 June 2015. Retrieved 26 August 2017.

[16] Kagan, M. L.; West, A. L.; Zante, C.; Calder, P. C. (2013). "Acute appearance of fatty acids in human plasma--a comparative study between polar-lipid rich oil from the microalgae Nannochloropsis oculata and krill oil in healthy young males". Lipids in Health and Disease. 12: 102. doi:10.1186/1476-511X-12-102. PMC 3718725. PMID 23855409.

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@@ Line 1: / Line 1: @@
-{{Chembox new
+{{Chembox
+| Watchedfields = changed
-|   Name = Eicosapentaenoic acid
+| verifiedrevid = 477000690
-|   ImageFile = EPAnumbering.png
+| Name = Eicosapentaenoic acid
-|   ImageSize = 400px
+| ImageFile = EPAnumbering.png
-|   ImageName = Eicosapentaenoic acid
+| ImageSize = 300px
-|   IUPACName = (5Z,8Z,11Z,14Z,17Z)-icosa-<br />&nbsp;5,8,11,14,17-pentaenoic acid
+| ImageName = Eicosapentaenoic acid
+| ImageFile1 = Eicosapentaenoic acid spacefill.png
+| ImageSize1 = 200px
+| PIN = (5''Z'',8''Z'',11''Z'',14''Z'',17''Z'')-Icosa-5,8,11,14,17-pentaenoic acid
+| OtherNames = (5''Z'',8''Z'',11''Z'',14''Z'',17''Z'')-5,8,11,14,17-eicosapentaenoic acid
 | Section1 = {{Chembox Identifiers
+| IUPHAR_ligand = 3362
-|   CASNo = 1553-41-9
+|   ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
-|   SMILES = CCC=CCC=CCC=CCC=CCC=CCCCC(=O)O
+| ChemSpiderID = 393682
-  }}
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = AAN7QOV9EA
+| 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-
+| InChIKey = JAZBEHYOTPTENJ-JLNKQSITBZ
+| ChEMBL_Ref = {{ebicite|correct|EBI}}
+| ChEMBL = 460026
+| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChI = 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-
+| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChIKey = JAZBEHYOTPTENJ-JLNKQSITSA-N
+| CASNo_Ref = {{cascite|correct|CAS}}
+| CASNo = 10417-94-4
+|   DrugBank_Ref = {{drugbankcite|correct|drugbank}}
+| DrugBank = DB00159
+| ChEBI_Ref = {{ebicite|correct|EBI}}
+| ChEBI = 28364
+| KEGG = C06428
+| PubChem = 446284
+| 3DMet = B00962
+| Beilstein = 1714433
+| SMILES = O=C(O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC
+}}
 | Section2 = {{Chembox Properties
 |   Formula = C<sub>20</sub>H<sub>30</sub>O<sub>2</sub>
 |   MolarMass = 302.451 g/mol
 |   MeltingPt =
+}}
+| Section3 = {{Chembox Hazards
+| GHSPictograms = {{GHS corrosion}}
+| GHSSignalWord = Danger
+| HPhrases = {{H-phrases|314}}
+| PPhrases = {{P-phrases|260|264|280|301+330+331|303+361+353|304+340|305+351+338|310|321|363|405|501}}
   }}
 }}
-'''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.
+'''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-trans isomerism|cis]]'' [[double bond]]s; 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]] [[eicosanoid]]s. EPA is both a precursor and the [[Hydrolysis|hydrolytic]] [[Metabolism|breakdown]] product of eicosapentaenoyl ethanolamide (EPEA: [[Carbon|C]]<sub>22</sub>[[Hydrogen|H]]<sub>35</sub>[[Biological functions of nitric oxide|NO]]<sub>2</sub>; 20:5,n-3).<ref>{{cite journal | vauthors = Lucanic M, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS | title = N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans | journal = Nature | volume = 473 | issue = 7346 | pages = 226–9 | date = May 2011 | pmid = 21562563 | pmc = 3093655 | doi = 10.1038/nature10007 | bibcode = 2011Natur.473..226L }}</ref>  Although studies of [[fish oil]] supplements, which contain both [[docosahexaenoic acid]] (DHA) and EPA, have failed to support claims of preventing [[Myocardial infarction|heart attacks]] or [[stroke]]s,<ref name="NYT-20150917-cz">{{cite news |last=Zimmer |first=Carl |name-list-style=vanc |author-link=Carl Zimmer |title=Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story |url=https://www.nytimes.com/2015/09/22/science/inuit-study-adds-twist-to-omega-3-fatty-acids-health-story.html |date=September 17, 2015 |work=[[The New York Times]] |access-date=October 11, 2015 |archive-date=January 9, 2019 |archive-url=https://web.archive.org/web/20190109042557/https://www.nytimes.com/2015/09/22/science/inuit-study-adds-twist-to-omega-3-fatty-acids-health-story.html |url-status=live }}</ref><ref name="NYT-20150330">{{cite news |last=O'Connor |first=Anahad |name-list-style=vanc |title=Fish Oil Claims Not Supported by Research |url=http://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not-supported-by-research/ |date=March 30, 2015 |work=The New York Times |access-date=October 11, 2015 |archive-date=May 28, 2018 |archive-url=https://web.archive.org/web/20180528110348/https://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not-supported-by-research/ |url-status=live }}</ref><ref name="JAMA-201403">{{cite journal | vauthors = Grey A, Bolland M | title = Clinical trial evidence and use of fish oil supplements | journal = JAMA Internal Medicine | volume = 174 | issue = 3 | pages = 460–2 | date = March 2014 | pmid = 24352849 | doi = 10.1001/jamainternmed.2013.12765 | url = http://archinte.jamanetwork.com/article.aspx?articleid=1787690 | doi-access = free | access-date = 2015-10-12 | archive-date = 2016-06-08 | archive-url = https://web.archive.org/web/20160608204741/http://archinte.jamanetwork.com/article.aspx?articleid=1787690 | url-status = live }}</ref> a recent multi-year study of Vascepa ([[Ethyl group|ethyl]] [[eicosapentaenoate]], the [[Ethyl group|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.<ref>{{cite journal | vauthors = Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM | title = Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia | journal = New England Journal of Medicine | volume = 380 | pages = 11–22 | date = January 3, 2019 | issue = 1 | doi = 10.1056/NEJMoa1812792 | pmid = 30415628 | doi-access = free }}</ref><ref name="REDUCE-IT">{{cite news |title=Vascepa® (icosapent ethyl) 26% Reduction in Key Secondary Composite Endpoint of Cardiovascular Death, Heart Attacks and Stroke Demonstrated in REDUCE-IT™ |url=https://investor.amarincorp.com/news-releases/news-release-details/vascepar-icosapent-ethyl-26-reduction-key-secondary-composite |date=November 10, 2018 |access-date=January 21, 2019 |archive-date=May 23, 2019 |archive-url=https://web.archive.org/web/20190523235050/https://investor.amarincorp.com/news-releases/news-release-details/vascepar-icosapent-ethyl-26-reduction-key-secondary-composite |url-status=dead }}</ref>
-:''EPA and its [[Metabolites#Metabolites|metabolites]] act in the body largely by their interactions with the metabolites of [[arachidonic acid]]; see [[Essential fatty acid interactions]] for detail.''
-EPA is a [[polyunsaturated]] [[fatty acid]] that acts as a precursor for [[prostaglandin|prostaglandin-3]] (which inhibits [[platelet]] aggregation), [[thromboxane]]-3, and [[leukotriene]]-5 groups (all [[eicosanoids]]).
 ==Sources==
-It is obtained in the human diet by [[Opsophagos|eating oily fish]] or  [[fish oil]]&mdash;[[cod]] liver, [[herring]], [[mackerel]], [[salmon]], [[menhaden]] and [[sardine]]. It is also found in human [[breast milk]].
+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).<ref>{{cite book|vauthors =((Committee on the Nutrient Requirements of Fish and Shrimp; National Research Council))|title=Nutrient requirements of fish and shrimp|date=2011|publisher=The National Academies Press|location=Washington, DC|isbn=978-0-309-16338-5}}</ref> Because of this extremely low conversion rate, fish primarily obtain it from the [[algae]] they consume.<ref name=vegan>{{cite web|url=http://www.vegetarian-dha-epa.co.uk/|title=Plant based sources of vegan & vegetarian Docosahexaenoic acid – DHA and Eicosapentaenoic acid EPA & Essential Fats|first=Yvonne|last=Bishop-Weston|name-list-style=vanc|access-date=2008-08-05|archive-url=https://web.archive.org/web/20130522103010/http://vegetarian-dha-epa.co.uk/|archive-date=2013-05-22|url-status=dead}}</ref> It is available to humans from some non-animal sources (e.g., commercially, from ''[[Yarrowia lipolytica]]'',<ref>{{Cite journal|last1=Xie|first1=Dongming|last2=Jackson|first2=Ethel N.|last3=Zhu|first3=Quinn|date=February 2015|title=Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production|journal=Applied Microbiology and Biotechnology|language=en|volume=99|issue=4|pages=1599–1610|doi=10.1007/s00253-014-6318-y|issn=0175-7598|pmc=4322222|pmid=25567511}}</ref> and from [[microalgae]] such as ''Nannochloropsis oculata'', ''Monodus subterraneus'',  ''Chlorella minutissima'' and ''[[Phaeodactylum tricornutum]]'',<ref>{{cite journal | journal = Journal of the American Oil Chemists' Society | date = 1998 | volume = 75 | issue = 3 | pages = 393–397 | title = Eicosapentaenoic acid and docosahexaenoic acid production potential of microalgae and their heterotrophic growth | first1 = Rema | last1 = Vazhappilly | first2 = Feng | last2 = Chen | name-list-style = vanc | doi=10.1007/s11746-998-0057-0| s2cid = 46917269 }}</ref><ref name="pmid22586907">{{cite journal | vauthors = Ratha SK, Prasanna R | title = Bioprospecting microalgae as potential sources of "Green Energy"—challenges and perspectives  | journal = Applied Biochemistry and Microbiology | volume = 48 | issue = 2 | pages = 109–125 | date = February 2012 | pmid = 22586907 | doi = 10.1134/S000368381202010X| s2cid = 18430041 }}</ref> which are being developed as a commercial source).<ref name=water4>{{cite web|url=http://www.nutraingredients.com/news/ng.asp?n=73324-water-omega-algae|title=Water 4 to introduce algae DHA/EPA as food ingredient|first=Jess|last=Halliday|name-list-style=vanc|date=12 January 2007|access-date=2007-02-09|archive-date=2007-01-16|archive-url=https://web.archive.org/web/20070116005656/http://www.nutraingredients.com/news/ng.asp?n=73324-water-omega-algae|url-status=live}}</ref> EPA is not usually found in higher plants, but it has been reported in trace amounts in [[Portulaca oleracea|purslane]].<ref>{{cite journal | url = http://apjcn.nhri.org.tw/server/APJCN/Volume11/vol11sup2/S163.pdf | last = Simopoulos | first = Artemis P | name-list-style = vanc | year = 2002 | title = Omega-3 fatty acids in wild plants, nuts and seeds | journal = Asia Pacific Journal of Clinical Nutrition | volume = 11 | issue = Suppl 2 | pages = S163–73 | doi = 10.1046/j.1440-6047.11.s.6.5.x | url-status = dead | archive-url = https://web.archive.org/web/20081217190429/http://apjcn.nhri.org.tw/server/APJCN/Volume11/vol11sup2/S163.pdf | archive-date = 2008-12-17 }}</ref> In 2013, it was reported that a genetically modified form of the plant [[Camelina sativa|camelina]] produced significant amounts of EPA.<ref>{{cite journal | vauthors = Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O | title = Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop | journal = The Plant Journal | volume = 77 | issue = 2 | pages = 198–208 | date = January 2014 | pmid = 24308505 | pmc = 4253037 | doi = 10.1111/tpj.12378 }}</ref><ref>{{cite journal | last = Coghlan | first = Andy | name-list-style = vanc | date = 4 January 2014 | title = Designed plant oozes vital fish oils | journal = New Scientist | volume = 221 | issue = 2950 | page = 12 | url = https://www.newscientist.com/article/mg22129503.000-designer-plants-have-vital-fish-oils-in-their-seeds.html#.Us3gItIUQUo | doi = 10.1016/s0262-4079(14)60016-6 | access-date = 26 August 2017 | archive-date = 1 June 2015 | archive-url = https://web.archive.org/web/20150601014206/http://www.newscientist.com/article/mg22129503.000-designer-plants-have-vital-fish-oils-in-their-seeds.html#.Us3gItIUQUo | url-status = live }}</ref>
-However, fish do not naturally produce EPA, but obtain it from the [[algae]] they consume.<ref name=autogenerated1>{{cite web|url=http://www.vegetarian-dha-epa.co.uk/|title=Plant based sources of vegan & vegetarian Docosahexaenoic acid - DHA and Eicosapentaenoic acid EPA & Essential Fats|author=Yvonne Bishop-Weston|accessdate=2008-08-05}}</ref> It is available from some non-animal sources&mdash;[[spirulina (dietary supplement)|spirulina]] and [[microalgae]]. Microalgae are being developed as a commercial source.<ref name=water4>{{cite web|url=http://www.nutraingredients.com/news/ng.asp?n=73324-water-omega-algae|title=Water 4 to introduce algae DHA/EPA as food ingredient|author=Jess Halliday |date=12/01/2007 |accessdate=2007-02-09}}</ref>  EPA is not usually found in higher plants, but it has been reported in trace amounts in [[purslane]].<ref name=SimopoulosWild>{{cite journal|url=http://www.healthyeatingclub.org/APJCN/Volume11/vol11sup6/S163.pdf
-|author= Simopoulos, Artemis P |year=2002|title=Omega-3 fatty acids in wild plants, nuts and seeds
-|journal=Asia Pacific Journal of Clinical Nutrition|volume= 11 |issue=s6|pages= S163–S173|
-doi=10.1046/j.1440-6047.11.s.6.5.|accessdate=2007-02-09|format={{Dead link|date=May 2008}}|doi_brokendate=2008-06-22}}</ref> Microalgae, and supplements derrived from it, are excellent alternative sources of EPA and other fatty acids, since fish often contain toxins due to pollution.<ref name=autogenerated1 />
-The human body can (and in case of a purely vegetarian diet often must, unless the aforementioned [[algae]] or supplements derived from them are consumed) also convert [[α-linolenic acid]] (ALA) to EPA, but this is much less efficient than the resorption of EPA from food containing it, and ALA is itself an essential fatty acid, an appropriate supply of which must be ensured. Because EPA is also a [[Precursor (chemistry)|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 DHA. Medical conditions like [[diabetes mellitus|diabetes]] or certain allergies may significantly limit the human body's capacity for metabolization of EPA from ALA.<ref>[http://www.foodsforlife.org.uk/nutrition/vegetarian-DHA-EPA.html Plant based sources of vegan & Vegetarian DHA & EPA and Omega 3 essential fatty acids<!-- Bot generated title -->]</ref>
+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 (chemistry)|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 mellitus|diabetes]] or certain allergies may significantly limit the human body's capacity for metabolization of EPA from ALA.
+== Forms ==
+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.<ref>{{cite journal | pmid=23855409 | year=2013 | last1=Kagan | first1=M. L. | last2=West | first2=A. L. | last3=Zante | first3=C. | last4=Calder | first4=P. C. | title=Acute appearance of fatty acids in human plasma--a comparative study between polar-lipid rich oil from the microalgae Nannochloropsis oculata and krill oil in healthy young males | journal=Lipids in Health and Disease | volume=12 | page=102 | doi=10.1186/1476-511X-12-102 | pmc=3718725 | doi-access=free }}</ref> Similarly, DHA or EPA in the [[lysophosphatidylcholine]] (LPC) form was found to be more efficient than triglyceride and [[phosphatidylcholine]]s (PC) in a 2020 study.<ref>{{cite journal |last1=Sugasini |first1=D |last2=Yalagala |first2=PCR |last3=Goggin |first3=A |last4=Tai |first4=LM |last5=Subbaiah |first5=PV |title=Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol. |journal=The Journal of Nutritional Biochemistry |date=December 2019 |volume=74 |pages=108231 |doi=10.1016/j.jnutbio.2019.108231 |pmid=31665653 |pmc=6885117}}</ref>
+{| class="wikitable sortable" style="width: auto;"
+|-
+! Base
+! EPA
+|-
+! [[Omega-3 acid ethyl esters|Ethyl ester]]
+| [[Ethyl eicosapentaenoic acid|EPA ethyl ester]]
+|-
+! [[Lysophosphatidylcholine]] (LPC, or lysoPC)
+| LPC-EPA, or lysoPC-EPA
+|-
+! [[Phosphatidylcholine]] (PC)
+| EPA-PC
+|-
+! [[Phospholipid]] (PL)
+| EPA-PL
+|-
+! [[Triglyceride]] (TG) or triacylglycerol (TAG)
+| EPA-TG, or EPA-TAG
+|-
+! Re-esterified [[triglyceride]] (rTG), or re-esterified triacylglycerol (rTAG)
+| EPA rTG, or r-TAG
+|}
+== Biosynthesis ==
+=== Aerobic eukaryote pathway ===
+[[File:Overview of biosynthesis of EPA.png|thumb|upright=1.5|EPA via aerobic eukaryote [[fatty acid synthesis]]]]
+Aerobic eukaryotes, specifically microalgae, [[moss]]es, [[Fungus|fungi]], and most animals (including humans), perform biosynthesis of EPA usually occurs as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase [[enzyme]]s. This pathway, originally identified in ''Thraustochytrium'', applies to these groups:<ref name=Qiu>{{Cite journal|date=2003-02-01|last=Qiu |first=Xiao |title=Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways|journal=Prostaglandins, Leukotrienes and Essential Fatty Acids |volume=68|issue=2|pages=181–186|doi=10.1016/S0952-3278(02)00268-5|issn=0952-3278|pmid=12538082}}</ref>
+# a desaturation at the sixth carbon of [[α-Linolenic acid|alpha-linolenic acid]] by a [[delta 6 desaturase|Δ6 desaturase]] to produce [[stearidonic acid]] (SDA, 18:4 ω-3),
+# elongation of the [[stearidonic acid]] by a Δ6 elongase to produce [[eicosatetraenoic acid]] (ETA, 20:4 ω-3),
+# desaturation at the fifth carbon of  [[eicosatetraenoic acid]] by a [[delta 5 desaturase|Δ5 desaturase]] to produce [[eicosapentaenoic acid]] (EPA, 20:5 ω-3),
+{{clear}}
+=== Polyketide synthase pathway ===
+[[File:LA--) EPA.pdf|thumb|upright=1.5|α-Linolenic acid to EPA via PKS]]
+Marine bacteria and the microalgae ''[[Schizochytrium]]'' use an anerobic [[polyketide synthase]] (PKS) pathway to synthesize DHA.<ref name=Qiu/> The PKS pathway includes six enzymes namely, 3-ketoacyl synthase (KS), 2 ketoacyl-[[Acyl carrier protein|ACP]]-reductase (KR), dehydrase (DH), enoyl reductase (ER), dehydratase/2-trans 3-cos isomerase (DH/2,3I), dehydratase/2-trans, and 2-cis isomerase (DH/2,2I). The biosynthesis of EPA varies in marine species, but most of the marine species' ability to convert C18 [[PUFA]] to LC-PUFA is dependent on the fatty acyl desaturase and elongase enzymes. The molecule basis of the enzymes will dictate where the double bond is formed on the resulting molecule.<ref>{{cite journal |last1=Monroig |first1=Óscar |last2=Tocher |first2=Douglas |last3=Navarro |first3=Juan |title=Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms |journal=Marine Drugs |date=2013-10-21 |volume=11 |issue=10 |pages=3998–4018 |doi=10.3390/md11103998 |pmid=24152561 |pmc=3826146|doi-access=free }}</ref>
+The proposed polyketide synthesis pathway of EPA in ''[[Shewanella]]'' (a marine bacterium) is a repetitive reaction of reduction, dehydration, and condensation that uses acetyl-CoA and malonyl-CoA as building blocks. The mechanism of α-linolenic acid to EPA involves the condensation of malonyl-CoA to the pre-existing α-linolenic acid by KS. The resulting structure is converted by NADPH dependent reductase, KR, to form an intermediate that is dehydrated by the DH enzyme. The final step is the NADPH-dependent reduction of a double bond in trans-2-enoyl-ACP via ER enzyme activity. The process is repeated to form EPA.<ref>{{cite journal |last1=Moi |first1=Ibrahim Musa |last2=Leow |first2=Adam Thean Chor |last3=Ali |first3=Mohd Shukuri Mohamad |last4=Rahman |first4=Raja Noor Zaliha Raja Abd. |last5=Salleh |first5=Abu Bakar |last6=Sabri |first6=Suriana |title=Polyunsaturated fatty acids in marine bacteria and strategies to enhance their production  |url=https://www.researchgate.net/publication/325068654 |journal=Applied Microbiology and Biotechnology |date=July 2018 |volume=102 |issue=14 |pages=5811–5826 |doi=10.1007/s00253-018-9063-9|pmid=29749565 |s2cid=13680225 }}</ref>
+{{clear}}
 ==Clinical significance==
+{{Further|Essential fatty acid interactions}}
-The US [[National Institute of Health]]'s MedlinePlus lists a large number of conditions in which EPA (alone or in concert with other ω-3 sources) is known or thought to be effective.<ref name=medline>{{cite web|url=http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html | title=MedlinePlus Herbs and Supplements: Omega-3 fatty acids, fish oil, alpha-linolenic acid | author = NIH Medline Plus| accessmonthday= February 14 |accessyear=2006}}
+[[File:Röding, Iduns kokbok.jpg|thumb|right|250px|[[Salmon]] is a rich source of EPA.]]
-</ref> Most of these involve its ability to lower [[inflammation]].
+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.<ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html |title=MedlinePlus Herbs and Supplements: Omega-3 fatty acids, fish oil, alpha-linolenic acid |author=NIH Medline Plus |access-date=February 14, 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060208023339/http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html |archive-date=February 8, 2006 }}</ref> 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&nbsp;mg/dL).
-Among [[omega-3 fatty acids]], in particular EPA is thought to possess beneficial potential in mental conditions, such as [[schizophrenia]].<ref name="pmid11356585">{{cite journal |author=Peet M, Brind J, Ramchand CN, Shah S, Vankar GK |title=Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia |
-url=http://jerrycott.com/user/peet.pdf |journal=[[Schizophrenia Research]] |volume=49 |issue=3 |pages=243–51 |year=2001 |pmid=11356585 |doi=  10.1016/S0920-9964(00)00083-9|accessdate=2007-12-21}}</ref><ref>Song C., Zhao S. ''Omega-3 fatty acid eicosapentaenoic acid. A new treatment for psychiatric and neurodegenerative diseases: a review of clinical investigations.'' University of Prince Edward Island, Department of Biomedical Sciences, AVC, 550 University Avenue, Charlottetown, PE, Canada. cai.song@nrc.gc.ca (Expert Opin Investig Drugs. 2007 Oct;16(10):1627-38.) [http://www.ncbi.nlm.nih.gov/pubmed/17922626?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Pub-Med]</ref>
-Several studies report an additional reduction in scores on symptom scales used to assess the severity of symptoms, when additional EPA is taken.
+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-analysis|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.<ref>{{cite journal |last1=AbuMweis |first1=S |last2=Jew |first2=S |last3=Tayyem |first3=R |last4=Agraib |first4=L |title=Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials. |journal=Journal of Human Nutrition and Dietetics |date=February 2018 |volume=31 |issue=1 |pages=67–84 |doi=10.1111/jhn.12493 |pmid=28675488|s2cid=8793334 |doi-access=free }}</ref><ref>{{cite journal |last1=Chen |first1=H |last2=Deng |first2=G |last3=Zhou |first3=Q |last4=Chu |first4=X |last5=Su |first5=M |last6=Wei |first6=Y |last7=Li |first7=L |last8=Zhang |first8=Z |title=Effects of eicosapentaenoic acid and docosahexaenoic acid versus α-linolenic acid supplementation on cardiometabolic risk factors: a meta-analysis of randomized controlled trials. |journal=Food & Function |date=26 March 2020 |volume=11 |issue=3 |pages=1919–1932 |doi=10.1039/c9fo03052b |pmid=32175534|s2cid=212730542 }}</ref> For example, in a study by Schaefer and colleagues of Tufts Medical School, patients were given either 600&nbsp;mg/day DHA alone, 600 or 1800&nbsp;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.<ref>{{cite journal |last1=Asztalos |first1=IB |last2=Gleason |first2=JA |last3=Sever |first3=S |last4=Gedik |first4=R |last5=Asztalos |first5=BF |last6=Horvath |first6=KV |last7=Dansinger |first7=ML |last8=Lamon-Fava |first8=S |last9=Schaefer |first9=EJ |title=Effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular disease risk factors: a randomized clinical trial. |journal=Metabolism: Clinical and Experimental |date=November 2016 |volume=65 |issue=11 |pages=1636–1645 |doi=10.1016/j.metabol.2016.07.010 |pmid=27733252}}</ref>
-Recent studies have suggested that EPA may affect depression, and importantly, suicidal behavior. One such study,<ref>{{cite journal |author=Huan M, Hamazaki K, Sun Y, Itomura M, Liu H, Kang W, Watanabe S, Terasawa K, Hamazaki T. |title=Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China | journal=     Biological psychiatry |volume=56 |issue=7 |pages=490–6 |year=2004 |pmid=1540784|doi=10.1016/j.biopsych.2004.06.028|url=http://www.journals.elsevierhealth.com/periodicals/bps/article/PIIS0006322304007061/abstract |format=abstract}}</ref> took blood samples of 100 suicide-attempt patients and compared the blood samples to those of controls and found that levels of Eicosapentaenoic acid were significantly lower in the washed red blood cells of the suicide-attempt patients.
+Ordinary consumers commonly obtain EPA and DHA from foods such as fatty fish,{{efn|1=Cooked salmon contain 500–1,500&nbsp;mg DHA and 300–1,000&nbsp;mg EPA per 100 grams of fish. See page: [[Salmon as food#Products|Salmon as food]].}} fish oil dietary supplements,{{efn|1=Omega-3 dietary oil supplements have no standard doses and generally salmon oil has more DHA than EPA while other white fishes have more EPA than DHA. One producer, [https://www.purealaskaomega.com/our-products/ Trident Food's Pure Alaska], for example reports per serving DHA 220&nbsp;mg and EPA 180&nbsp;mg for their salmon oil (total omega-3 = 600&nbsp;mg), but DHA 144&nbsp;mg and EPA 356&nbsp;mg for pollock fish oil (total omega-3 = 530&nbsp;mg). Equivalent products from another producer, [https://www.puritan.com/fish-oils-056 Fish Oils, Puritan's Pride], reports DHA 180&nbsp;mg and EPA 150&nbsp;mg for their salmon oil product (total omega-3 = 420&nbsp;mg), but DHA 204&nbsp;mg and EPA 318&nbsp;mg for fish oil derived from anchovy, sardine, and mackerel (total omega-3 = 600&nbsp;mg). For information and comparison purposes only, no endorsements are implied. }} and less commonly from [[seaweed oil|algae oil]] supplements{{efn|1=Many plant sources of omega-3s are rich in ALA but completely lack EPA and DHA. The exception is algae derived oils. Because there are more commercially-grown algae sources of DHA than EPA, algae omega-3 supplements typically contain more DHA than EPA. For example, [https://www.nordic.com/products/algae-omega/?variant=39472182919352 Nordic Naturals] reports per serving DHA 390&nbsp;mg and EPA 195&nbsp;mg (total omega-3 = 715&nbsp;mg), [https://calgee.com/products/omega-3-supplement Calgee] reports DHA 300&nbsp;mg and EPA 150&nbsp;mg (total omega-3 = 550&nbsp;mg) and so on, but [https://iwilife.com/products/epa-omega-3-supplement?variant=41981748117704 iwi] reports EPA 250&nbsp;mg (total omega-3 = 254&nbsp;mg). For information and comparison purposes only, no endorsements are implied.}} 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.<ref>{{cite journal |last1=Harris |first1=WS |last2=Leonard |first2=D |last3=Radford |first3=NB |last4=Barlow |first4=CE |last5=Steele |first5=MR |last6=Farrell |first6=SW |last7=Pavlovic |first7=A |last8=Willis |first8=BL |last9=DeFina |first9=LF |title=Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study. |journal=Journal of Clinical Lipidology |date=January 2021 |volume=15 |issue=1 |pages=212–217 |doi=10.1016/j.jacl.2020.11.011 |pmid=33339757|s2cid=229325648 }}</ref> 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.
-EPA has inhibitory effect on  [[CYP2C9]] and [[CYP2C19]] hepatic enzymes. At high dose, it may also inhibit the activity of [[CYP2D6]] and [[CYP3A4]], important enzymes involved in drug metabolism.<ref name="pmid16978661">{{cite journal
-|author=Yao HT, Chang YW, Lan SJ, Chen CT, Hsu JT, Yeh TK
-|title=The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes
-|journal=Life Sci.
-|volume=79
-|issue=26
-|pages=2432–40
-|year=2006
-|pmid=16978661
-|doi=10.1016/j.lfs.2006.08.016
-}}</ref>
+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.<ref name=":0">{{cite journal | vauthors = Bent S, Bertoglio K, Hendren RL | title = Omega-3 fatty acids for autistic spectrum disorder: a systematic review | journal = Journal of Autism and Developmental Disorders | volume = 39 | issue = 8 | pages = 1145–54 | date = August 2009 | pmid = 19333748 | pmc = 2710498 | doi = 10.1007/s10803-009-0724-5 }}</ref><ref>{{cite journal | vauthors = Mankad D, Dupuis A, Smile S, Roberts W, Brian J, Lui T, Genore L, Zaghloul D, Iaboni A, Marcon PM, Anagnostou E | title = A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism | journal = Molecular Autism | volume = 6 | pages = 18 | date = 2015-03-21 | pmid = 25798215 | pmc = 4367852 | doi = 10.1186/s13229-015-0010-7 | doi-access = free }}</ref>
-==See also==
-* [[Chlorella]]
-* [[Cyanobacteria]]
-* [[Docosahexaenoic acid]]
-* [[List of omega-3 fatty acids]]
-* [[Polyunsaturated fatty acid]]s
-* [[Snake oil]]
-* [[Wakame]]
+In addition, studies have shown that omega-3 fatty acids may be useful for treating [[Depression (mood)|depression]].<ref>{{cite journal |last1=Freeman |first1=Marlene P. |last2=Hibbeln |first2=Joseph R. |last3=Wisner |first3=Katherine L. |last4=Davis |first4=John M. |last5=Mischoulon |first5=David |last6=Peet |first6=Malcolm |last7=Keck |first7=Paul E. |last8=Marangell |first8=Lauren B. |last9=Richardson |first9=Alexandra J. |last10=Lake |first10=James |last11=Stoll |first11=Andrew L. |title=Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry |journal=The Journal of Clinical Psychiatry |date=December 2006 |volume=67 |issue=12 |pages=1954–1967 |doi=10.4088/jcp.v67n1217 |pmid=17194275 |url=https://pubmed.ncbi.nlm.nih.gov/17194275/ |issn=1555-2101 |access-date=2022-10-13 |archive-date=2020-09-20 |archive-url=https://web.archive.org/web/20200920045905/https://pubmed.ncbi.nlm.nih.gov/17194275/ |url-status=live }}</ref><ref>{{cite web |last1=Ilardi |first1=Stephen |title=Therapeutic Lifestyle Change. A new treatment for depression |url=http://tlc.ku.edu/elements |website=Therapeutic Lifestyle Change (TLC) |date=28 April 2015 |access-date=9 November 2019 |language=en |quote=We were never designed for the sedentary, indoor, sleep-deprived, socially-isolated, fast-food-laden, frenetic pace of modern life. |archive-date=9 November 2019 |archive-url=https://web.archive.org/web/20191109184424/http://tlc.ku.edu/elements |url-status=live }}</ref>
-==References==
+EPA and DHA [[ethyl ester]]s (all forms) may be absorbed less well, thus work less well, when taken on an empty stomach or with a low-fat meal.<ref name="NLApt2-2015">{{cite journal | vauthors = Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA | title = National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2 | journal = Journal of Clinical Lipidology | volume = 9 | issue = 6 Suppl | pages = S1–122.e1 | year = 2015 | pmid = 26699442 | doi = 10.1016/j.jacl.2015.09.002 | doi-access = free }}</ref>
+== Notes ==
+{{notelist}}
+== References ==
+{{Reflist|25em}}
+== External links ==
+* [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=EPA  EPA bound to proteins] in the [[Protein Data Bank|PDB]]
+*[https://pubchem.ncbi.nlm.nih.gov/compound/5283450 Eicosapentaenoyl Ethanolamide]; [[Anandamide]] (20:5, n-3); EPEA. - [[PubChem]]
-[[Image:Röding, Iduns kokbok.jpg|thumb|right|250px|Salmon is a rich source of EPA.]]
-<references/>
 {{Eicosanoids}}
 {{Fatty acids}}
+{{Mood stabilizers }}
+{{Authority control}}
 [[Category:Fatty acids]]
-[[Category:Carboxylic acids]]
+[[Category:Alkenoic acids]]
-[[da:Icosapentaensyre]]
-[[de:Eicosapentaensäure]]
-[[es:Ácido eicosapentaenoico]]
-[[fr:Acide éicosapentaènoïque]]
-[[nl:Eicosapentaeenzuur]]
-[[ja:エイコサペンタエン酸]]
-[[pl:Kwas eikozapentaenowy]]
-[[pt:Ácido eicosapentaenóico]]
-[[sv:EPA (fettsyra)]]

v t e Lipids: fatty acids
Saturated	Propionic (C3) Butyric (C4) Valeric (C5) Caproic (C6) Enanthic (C7) Caprylic (C8) Pelargonic (C9) Capric (C10) Undecylic (C11) Lauric (C12) Tridecylic (C13) Myristic (C14) Pentadecylic (C15) Palmitic (C16) Margaric (C17) Stearic (C18) Nonadecylic (C19) Arachidic (C20) Heneicosylic (C21) Behenic (C22) Tricosylic (C23) Lignoceric (C24) Pentacosylic (C25) Cerotic (C26) Carboceric (C27) Montanic (C28) Nonacosylic (C29) Melissic (C30) Hentriacontylic (C31) Lacceroic (C32) Psyllic (C33) Geddic (C34) Ceroplastic (C35) Hexatriacontylic (C36) Heptatriacontanoic (C37) Octatriacontanoic (C38) Nonatriacontanoic (C39) Tetracontanoic (C40)
ω−3 Unsaturated	Octenoic (8:1) Decenoic (10:1) Decadienoic (10:2) Lauroleic (12:1) Laurolinoleic (12:2) Myristovaccenic (14:1) Myristolinoleic (14:2) Myristolinolenic (14:3) Palmitolinolenic (16:3) Palmitidonic (16:4) α-Linolenic (18:3) Stearidonic (18:4) α-Parinaric (18:4) Dihomo-α-linolenic (20:3) Eicosatetraenoic (20:4) Eicosapentaenoic (20:5) Clupanodonic (22:5) Docosahexaenoic (22:6) 9,12,15,18,21-Tetracosapentaenoic (24:5) 6,9,12,15,18,21-Tetracosahexaenoic (24:6)
ω−5 Unsaturated	Myristoleic (14:1) Palmitovaccenic (16:1) α-Eleostearic (18:3) β-Eleostearic (trans-18:3) Punicic (18:3) 7,10,13-Octadecatrienoic (18:3) 9,12,15-Eicosatrienoic (20:3) β-Eicosatetraenoic (20:4)
ω−6 Unsaturated	8-Tetradecenoic (14:1) 12-Octadecenoic (18:1) Linoleic (18:2) Linolelaidic (trans-18:2) γ-Linolenic (18:3) Calendic (18:3) Pinolenic (18:3) Dihomo-linoleic (20:2) Dihomo-γ-linolenic (20:3) Sciadonic (20:3) Arachidonic (20:4) Adrenic (22:4) Osbond (22:5)
ω−7 Unsaturated	Palmitoleic (16:1) Vaccenic (18:1) Rumenic (18:2) Paullinic (20:1) 7,10,13-Eicosatrienoic (20:3)
ω−9 Unsaturated	Oleic (18:1) Elaidic (trans-18:1) Gondoic (20:1) Erucic (22:1) Nervonic (24:1) 8,11-Eicosadienoic (20:2) Mead (20:3)
ω−10 Unsaturated	Sapienic (16:1)
ω−11 Unsaturated	Gadoleic (20:1)
ω−12 Unsaturated	4-Hexadecenoic (16:1) Petroselinic (18:1) 8-Eicosenoic (20:1)

v t e Mood stabilizers
Anticonvulsants	Carbamazepine Lamotrigine Oxcarbazepine Valproate Valnoctamide Valproate pivoxil Valpromide
Atypical antipsychotics	Aripiprazole Asenapine Cariprazine Clozapine Lurasidone Olanzapine (+fluoxetine) Paliperidone Quetiapine Risperidone Ziprasidone
Others	Ketamine Lithium (lithium acetate, lithium carbonate, lithium chloride, lithium citrate, lithium hydroxide, lithium orotate) Omega-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid)