Eicosapentaenoic acid

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Eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid spacefill.png
Names
IUPAC name
(5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoic acid
Identifiers
10417-94-4 YesY
ChEBI CHEBI:28364 YesY
ChEMBL ChEMBL460026 YesY
ChemSpider 393682 YesY
DrugBank DB00159 YesY
3362
Jmol interactive 3D Image
UNII AAN7QOV9EA YesY
Properties
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).
YesY verify (what is YesYN ?)
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[edit]

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[edit]

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[edit]

  1. ^ Zimmer, Carl (September 17, 2015). "Inuit Study Adds Twist to Omega-3 Fatty Acids’ Health Story". New York Times. Retrieved October 11, 2015. 
  2. ^ O'Connor, Anahad (March 30, 2015). "Fish Oil Claims Not Supported by Research". New York Times. Retrieved October 11, 2015. 
  3. ^ Grey, Andrew; Bolland, Mark (March 2014). "Clinical Trial Evidence and Use of Fish Oil Supplements". JAMA Internal Medicine 174 (3): 460–462. doi:10.1001/jamainternmed.2013.12765. Retrieved October 11, 2015. 
  4. ^ 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 0-309-16338-2. 
  5. ^ Yvonne Bishop-Weston. "Plant based sources of vegan & vegetarian Docosahexaenoic acid - DHA and Eicosapentaenoic acid EPA & Essential Fats". Retrieved 2008-08-05. 
  6. ^ Jess Halliday (12 January 2007). "Water 4 to introduce algae DHA/EPA as food ingredient". Retrieved 2007-02-09. 
  7. ^ Simopoulos, Artemis P (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. 
  8. ^ Ruiz-Lopez, N.; Haslam, R. P.; Napier, J. A.; 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. 
  9. ^ Coghlan, Andy (4 January 2014) "Designed plant oozes vital fish oils"' New Scientist, volume 221, issue 2950, page 12, also available on the Internet at [1]
  10. ^ 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. 
  11. ^ Weintraub, HS (2014). "Overview of prescription omega-3 fatty acid products for hypertriglyceridemia". Postgrad Med. (126): 7–18. doi:10.3810/pgm.2014.11.2828. PMID 25387209. Retrieved 16 April 2015. 
  12. ^ Bays, HE; Ballantyne, CM; Kastelein, JJ; Isaacsohn, JL; Braeckman, RA; Soni, PN (2011). "Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial)". Am J Cardiol (108): 682–690. doi:10.1016/j.amjcard.2011.04.015. PMID 21683321. Retrieved 16 April 2015. 
  13. ^ Jacobson, TA; Ito, MK; Maki, KC (2014). "National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 – executive summary". J Clin Lipidol (8): 473–488. PMID 25234560. Retrieved 16 April 2015. 
  14. ^ Phaniendra, A; Jestadi, DB; Periyasamy, L (2015). "Free radicles: properties, sources, targets and their implication in various diseases". Indian J Clin Biochem 1 (30). doi:10.1007/s12291-014-0446-0. 
  15. ^ Kohashi, K; Nakagomi, A; Saiki, Y (2015). "Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia". Journal of Atherosclerosis and Thrombosis. doi:10.5551/jat.21022. PMID 24670266. 
  16. ^ Kelley, NS; Yoshida, Y; Erickson, KL (2014). "Do n-3 polyunsaturated fatty acids increase or decrease lipid peroxidation in humans?". Metab Syndr Relat Disord 12 (8). doi:10.1089/met.2014.0045. PMID 25045922. 
  17. ^ a b Mason, RP; Jacob, R; Beauregard, G; Rowe, J (2011). "Comparative lipid antioxidant effects of omega-3 fatty acids in combination with HMG-CoA reductase inhibitors [abstract]". J Clin Lipidol. 5: 201. 
  18. ^ Mason, RP; Jacob, R; Beauregard, G; Malinski, T (2015). "Eicosapentaenoic acid reduces small dense low density lipoprotein oxidation and improves endothelial function in vitro as compared to other triglyceride-lowering agents [abstract]". J Am Coll Cardiol 65: A2139. 
  19. ^ a b Mason, RP; Jacob, RF (2015). "Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism". Biochim Biophys Acta 1848 (2): 502–509. doi:10.1016/j.bbamem.2014.10.016. PMID 25449996. 
  20. ^ Mason, RP; Jacob, RF; Corbalan, J; Malinsky, T. "Combination treatment with eicosapentaenoic acid and atorvastatin active metabolite reverses endothelial dysfunction in HUVECs exposed to oxidized LDL [abstract].Presented at the DEUEL Conference on Lipids, March 3-6, 2015, Monterey, CA". 
  21. ^ Peet M, Brind J, Ramchand CN, Shah S, Vankar GK (2001). "Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia" (PDF). Schizophrenia Research 49 (3): 243–51. doi:10.1016/S0920-9964(00)00083-9. PMID 11356585. 
  22. ^ Song C, Zhao S (Oct 2007). "Omega-3 fatty acid eicosapentaenoic acid. A new treatment for psychiatric and neurodegenerative diseases: a review of clinical investigations". Expert Opin Investig Drugs 16 (10): 1627–38. doi:10.1517/13543784.16.10.1627. PMID 17922626. 
  23. ^ Martins, JG (Oct 2009). "EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials.". Journal of the American College of Nutrition 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID 20439549. 
  24. ^ Yao HT, Chang YW, Lan SJ, Chen CT, Hsu JT, Yeh TK (2006). "The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes". Life Sci. 79 (26): 2432–40. doi:10.1016/j.lfs.2006.08.016. PMID 16978661. 
  25. ^ Braeckman, RA; Stirtan, WG; Soni, PN (2014). ". Effect of concomitant icosapent ethyl (eicosapentaenoic Acid ethyl ester) on the pharmacokinetics of atorvastatin.". Drugs R D 14: 159–164. doi:10.1007/s40268-014-0053-9. PMID 24973042. Retrieved 20 April 2015. 
  26. ^ Braeckman, RA; Stirtan, WG; Soni, PN (2014). "Effects of icosapent ethyl (eicosapentaenoic acid ethyl ester) on pharmacokinetic parameters of rosiglitazone in healthy subjects". Clin Pharmacol Drug Dev. 4: 143–148. doi:10.1002/cpdd.150. 
  27. ^ Braeckman, RA; Stirtan, WG; Soni, PN (2014). "Phase 1 study of the effect of icosapent ethyl on warfarin pharmacokinetic and anticoagulation parameters". Clin Drug Investig 34: 449–456. doi:10.1007/s40261-014-0194-1. PMID 24760401. Retrieved 20 April 2015. 
  28. ^ Braeckman, RA; Stirtan, WG; Soni, PN (2015). "Effect of concomitant icosapent ethyl (eicosapentaenoic Acid ethyl ester) on the pharmacokinetics of atorvastatin" 35: 45–51. doi:10.1007/s40261-014-0252-8. PMID 25471740. 
  29. ^ Hardman,W Elaine (2004). "(n-3)Fatty Acids and Cancer Therapy". Journal of Nutrition 134 (12): 3427S–3430S. PMID 15570049.