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Names | |
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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 | |
3D model (JSmol) | |
3DMet | |
1714433 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
DrugBank | |
ECHA InfoCard | 100.117.069 |
KEGG | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C20H30O2 | |
Molar mass | 302.451 g/mol |
Hazards | |
GHS labelling: | |
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Danger | |
H314 | |
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). |
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: C 22 H 35 NO 2; 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]
Base | EPA |
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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 |
Aerobic eukaryotes, specifically microalgae, mosses, fungi, and most animals (including humans), perform biosynthesis of EPA usually 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]
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]
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]
Omega−3 fatty acids, also called Omega−3 oils, ω−3 fatty acids, Ω-3 Fatty acids or n−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure. They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. DHA and EPA accumulate in fish that eat these algae. Common sources of plant oils containing ALA include walnuts, edible seeds, and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils, and algae oil.
Essential fatty acids, or EFAs, are fatty acids that are required by humans and other animals for normal physiological function that cannot be synthesized in the body. As they are not synthesized in the body, the essential fatty acids – alpha-linolenic acid (ALA) and linoleic acid – must be obtained from food or from a dietary supplement. Essential fatty acids are needed for various cellular metabolic processes and for the maintenance and function of tissues and organs. These fatty acids also are precursors to vitamins, cofactors, and derivatives, including prostaglandins, leukotrienes, thromboxanes, lipoxins, and others.
α-Linolenic acid, also known as alpha-linolenic acid (ALA), is an n−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, walnuts, chia, hemp, and many common vegetable oils.
Oily fish are fish species with oil (fats) in soft tissues and in the coelomic cavity around the gut. Their fillets may contain up to 30% oil, although this figure varies both within and between species. Examples of oily fish include small forage fish such as sardines, herring and anchovies, and other larger pelagic fish such as salmon, trout, tuna, swordfish and mackerel.
gamma-Linolenic acid or GLA is an n−6, or omega-6, fatty acid found primarily in seed oils. When acting on GLA, arachidonate 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.
Krill oil is an extract prepared from a species of Antarctic krill, Euphausia superba. Processed krill oil is commonly sold as a dietary supplement. Two components of krill oil are omega-3 fatty acids similar to those in fish oil, and phospholipid-derived fatty acids (PLFA), mainly phosphatidylcholine. Fishing for krill where previously the focus was on marine life of higher trophic level is an example of fishing down the food web.
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body and improve hypertriglyceridemia. There has been a great deal of controversy in the 21st century about the role of fish oil in cardiovascular disease, with recent meta-analyses reaching different conclusions about its potential impact.
Vegetarian nutrition is the set of health-related challenges and advantages of vegetarian diets.
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(n-3). It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk, fatty fish, fish oil, or algae oil. The consumption of DHA contributes to numerous physiological benefits, including cognition. As a component of neuronal membranes, the function of DHA is to support neuronal conduction and to allow the optimal functioning of neuronal membrane proteins.
Dihomo-γ-linolenic acid (DGLA) is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 (ω−6). DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product of γ-linolenic acid. GLA, in turn, is a desaturation product of linoleic acid. DGLA is made in the body by the elongation of GLA, by an efficient enzyme which does not appear to suffer any form of (dietary) inhibition. DGLA is an extremely uncommon fatty acid, found only in trace amounts in animal products.
Fatty acid desaturases are a family of enzymes that convert saturated fatty acids into unsaturated fatty acids and polyunsaturated fatty acids. For the common fatty acids of the C18 variety, desaturases convert stearic acid into oleic acid. Other desaturases convert oleic acid into linoleic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.
There is a wide variety of fatty acids found in nature. Two classes of fatty acids are considered essential, the omega-3 and omega-6 fatty acids. Essential fatty acids are necessary for humans but cannot be synthesized by the body and must therefore be obtained from food. Omega-3 and omega-6 are used in some cellular signaling pathways and are involved in mediating inflammation, protein synthesis, and metabolic pathways in the human body.
Docosapentaenoic acid (DPA) designates any straight open chain polyunsaturated fatty acid (PUFA) which contains 22 carbons and 5 double bonds. DPA is primarily used to designate two isomers, all-cis-4,7,10,13,16-docosapentaenoic acid and all-cis-7,10,13,16,19-docosapentaenoic acid. They are also commonly termed n-6 DPA and n-3 DPA, respectively; these designations describe the position of the double bond being 6 or 3 carbons closest to the (omega) carbon at the methyl end of the molecule and is based on the biologically important difference that n-6 and n-3 PUFA are separate PUFA classes, i.e. the omega-6 fatty acids and omega-3 fatty acids, respectively. Mammals, including humans, can not interconvert these two classes and therefore must obtain dietary essential PUFA fatty acids from both classes in order to maintain normal health.
Linoleoyl-CoA desaturase (also Delta 6 desaturase, EC 1.14.19.3) is an enzyme that converts between types of fatty acids, which are essential nutrients in the human body. The enzyme mainly catalyzes the chemical reaction
Omega-3-acid ethyl esters are a mixture of ethyl eicosapentaenoic acid and ethyl docosahexaenoic acid, which are ethyl esters of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil. Together with dietary changes, they are used to treat high blood triglycerides which may reduce the risk of pancreatitis. They are generally less preferred than statins, and use is not recommended by NHS Scotland as the evidence does not support a decreased risk of heart disease. Omega-3-acid ethyl esters are taken by mouth.
Ethyl eicosapentaenoic acid, sold under the brand name Vascepa among others, is a medication used to treat dyslipidemia and hypertriglyceridemia. It is used in combination with changes in diet in adults with hypertriglyceridemia ≥ 150 mg/dL. Further, it is often required to be used with a statin.
Schizochytrium is a genus of unicellular eukaryotes in the family Thraustochytriaceae, which are found in coastal marine habitats. They are assigned to the Stramenopiles (heterokonts), a group which also contains kelp and various microalgae.
Omega-3 carboxylic acids (Epanova) is a formerly marketed yet still not an Food And Drug Administration (FDA) approved prescription medication–since taken off market by the manufacturer–used alongside a low fat and low cholesterol diet that lowers high triglyceride (fat) levels in adults with very high levels. This was the third class of fish oil-based drug, after omega-3 acid ethyl esters and ethyl eicosapentaenoic acid (Vascepa), to be approved for use as a drug. The first approval by US Food and Drug Administration was granted 05 May 2014. These fish oil drugs are similar to fish oil dietary supplements, but the ingredients are better controlled and have been tested in clinical trials. Specifically, Epanova contained at least 850 mg omega-3-acid ethyl esters per 1 g capsule.
In general, cognitive support diets are formulated to include nutrients that have a known role in brain development, function and/or maintenance, with the goal of improving and preserving mental processes such as attentiveness, short-term and long-term memory, learning, and problem solving. Currently, there is very little conclusive research available regarding cat cognition as standardized tests for evaluating cognitive ability are less established and less reliable than cognitive testing apparatus used in other mammalian species, like dogs. Much of what is known about feline cognition has been inferred from a combination of owner-reported behaviour, brain necropsies, and comparative cognitive neurology of related animal models. Cognition claims appear primarily on kitten diets which include elevated levels of nutrients associated with optimal brain development, although there are now diets available for senior cats that include nutrients to help slow the progression of age-related changes and prevent cognitive decline. Cognition diets for cats contain a greater portion of omega-3 fatty acids, especially docosahexaenoic acid (DHA) as well as eicosapentaenoic acid (EPA), and usually feature a variety of antioxidants and other supporting nutrients thought to have positive effects on cognition.
Seaweed oil, also called algae oil or algal oil, is used for making food, with the purified product almost colorless and odorless. It is also under development as a possible alternative fuel and manufacturing agent.
We were never designed for the sedentary, indoor, sleep-deprived, socially-isolated, fast-food-laden, frenetic pace of modern life.