Ingredient intelligence · non-production preview

Eicosapentaenoic acid (EPA)

Also known as EPA, Eicosapentaenoic acid

Not medically reviewed

fatty acidentity:ingredient:epaCompare this ingredient View evidence

Identity structure

Parent and form relationships

Ingredients, supplement concepts, supplement-form projections, and commercial products remain separate records.

Parent supplement

Omega-3entity:supplement:omega-3

Related ingredient forms

Docosahexaenoic acid (DHA)fatty acid

Origin is not a quality score

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Evidence availability

Direct ingredient evidence boundaries

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Identity and what it is

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Structural characterization

Evidence profile

No overall rating assigned

Evidence source: NIH ODS evidence synthesis
Linked references: 20 identified
Human evidence: Human evidence identified
Randomized trials: Randomized trials not identified in the frozen metadata
Reviews and meta-analyses: Systematic reviews or meta-analyses not identified in the frozen metadata
Evidence recency: 2004–2015
Source-described consistency: Not characterized in these source blocks
MEDucated evidence rating: Not assigned

Reference counts describe frozen source associations; a larger count does not establish stronger evidence.

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Evidence types identified

Study type could not be determined20

Source-described limitations

No explicit limitation phrase was identified in these imported source blocks.

Classified references

Jones PJH, Rideout T. Lipids, sterols, and their metabolites. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Jones PJH, Papamandjaris AA. Lipids: cellular metabolism. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:132-48.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Harris WS. Omega-3 fatty acids. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:577-86.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM. Advances in our understanding of oxylipins derived from dietary PUFAs. Adv Nutr 2015;6:513-40. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med 2008;233:674-88. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
James M, Proudman S, Cleland L. Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc 2010;69:316-23. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Wang C, Chung M, Lichtenstein A, Balk E, Kupelnick B, DeVine D, et al. Effects of omega-3 fatty acids on cardiovascular disease. Summary, evidence report/technology assessment no. 94. (Prepared by the Tufts New England Medical Center Evidence-based Practice Center, Boston, MA.) AHRQ Publication No. 04-E009-1. Agency for Healthcare Research and Quality, 2004.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Stanley JC, Elsom RL, Calder PC, Griffin BA, Harris WS, Jebb SA, et al. UK Food Standards Agency workshop report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. Br J Nutr 2007;98:1305-10. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Harris WS, Davidson MH. RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 2014;106:dju019. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Fritsche KL. Too much linoleic acid promotes inflammation-doesn't it? Prostaglandins Leukot Essent Fatty Acids 2008;79:173-5. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, et al. Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol 2011;173:1429-39. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, et al. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 2013;105:1132-41. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, et al. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation 2004;110:1645-9. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessed
Harris WS. Are n-3 fatty acids still cardioprotective? Curr Opin Clin Nutr Metab Care 2013;16:141-9. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Sun Q, Ma J, Campos H, Hankinson SE, Hu FB. Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women. Am J Clin Nutr 2007;86:74-81. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessed
Agency for Healthcare Research and Quality. Omega-3 fatty acids and cardiovascular disease - update. 2015.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med 2004;39:212-20. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Harris WS. The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr 2008;87:1997S-2002S. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Metcalf RG, Cleland LG, Gibson RA, Roberts-Thomson KC, Edwards JR, Sanders P, et al. Relation between blood and atrial fatty acids in patients undergoing cardiac bypass surgery. Am J Clin Nutr 2010;91:528-34. [PubMed abstract]
Study type could not be determined · Population basis: human · Directness: not assessed
von Schacky C. Use of red blood cell fatty-acid profiles as biomarkers in cardiac disease. Biomark Med 2009;3:25-32. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed

Read imported source wording

Omega-3 fatty acids (omega-3s) have a carbon–carbon double bond located three carbons from the methyl end of the chain. Omega-3s, sometimes referred to as n-3s, are present in certain foods such as flaxseed and fish as well as dietary supplements such as fish oil. Several different omega-3s exist, but the majority of scientific research focuses on three: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA contains 18 carbon atoms, whereas EPA and DHA are considered long-chain (LC) omega-3s because EPA contains 20 carbons and DHA contains 22.

PUFAs are frequently designated by their number of carbon atoms and double bonds. ALA, for example, is known as C18:3n-3 because it has 18 carbons and 3 double bonds and is an n-3, or omega-3, fatty acid. Similarly, EPA is known as C20:5n-3 and DHA as C22:6n-3. Omega-6 fatty acids (omega-6s) have a carbon–carbon double bond that is six carbons away from the methyl end of the fatty acid chain. Linoleic acid (C18:2n-6) and arachidonic acid (C20:4n-6) are two of the major omega-6s.

The human body can only form carbon–carbon double bonds after the ninth carbon from the methyl end of a fatty acid [1]. Therefore, ALA and linoleic acid are considered essential fatty acids, meaning that they must be obtained from the diet [2]. ALA can be converted into EPA and then to DHA, but the conversion (which occurs primarily in the liver) is very limited, with reported rates of less than 15% [3]. Therefore, consuming EPA and DHA directly from foods and/or dietary supplements is the only practical way to increase levels of these fatty acids in the body.

ALA is present in plant oils, such as flaxseed, soybean, and canola oils [3]. DHA and EPA are present in fish, fish oils, and krill oils, but they are originally synthesized by microalgae at the base of the marine food chain, not by the fish. As microalgae move up the food chain, fish acquire the omega-3s and accumulate them in their tissues [3].

The eicosanoids made from omega-6s are generally more potent mediators of inflammation, vasoconstriction, and platelet aggregation than those made from omega-3s, although there are some exceptions [3,7]. Because both classes of fatty acids compete for the same desaturation enzymes, ALA is a competitive inhibitor of linoleic acid metabolism and vice versa [8]. Similarly, EPA and DHA can compete with arachidonic acid for the synthesis of eicosanoids. Thus, higher concentrations of EPA and DHA than arachidonic acid tip the eicosanoid balance toward less inflammatory activity [9].

Some researchers propose that the relative intakes of omega-6s and omega-3s—the omega-6/omega-3 ratio—may have important implications for the pathogenesis of many chronic diseases, such as cardiovascular disease (CVD) and cancer [8], but the optimal ratio—if any—has not been defined [10]. Others have concluded that such ratios are too nonspecific and are insensitive to individual fatty acid levels [11-13]. Most agree that raising EPA and DHA blood levels is far more important than lowering linoleic acid or arachidonic acid levels.

Currently, most clinicians do not assess omega-3 status, but it can be done by measuring individual omega-3s in plasma or serum phospholipids and expressing them as the percentage of total phospholipid fatty acids by weight [14-16]. Experts have not established normal ranges, but mean values for serum or plasma phospholipid EPA plus DHA among U.S. adults not taking omega-3 supplements are about 3%–4% [14-16]. Plasma and serum fatty acid values, however, can vary substantially based on an individual's most recent meal, so they do not reflect long-term dietary consumption [3,17].

It is also possible to assess omega-3 status via analysis of erythrocyte fatty acids, a measurement that reflects longer term intakes over approximately the previous 120 days [18,19]. The omega-3 index proposed by Harris and von Schacky reflects the content of EPA plus DHA in erythrocyte membranes expressed as a percentage of total erythrocyte fatty acids [20,21]. This index can be used as a surrogate for assessing tissue levels of EPA plus DHA [16,22,23]. EPA and DHA typically comprise about 3%–5% of erythrocyte fatty acids in Western populations with low fish intakes. In Japan, where fish consumption is high, erythrocyte EPA and DHA levels are about twice those of Western populations [3].

Where did MEDucated get this?

Omega-3 Fatty Acids

Publisher: NIH Office of Dietary Supplements
Revision: August 22, 2025
Source fingerprint: 80b4434afaf71303420a09ab193258a2d656c3bdec58a108fe3d14961d1bb750
Source blocks: ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:2, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:3, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:4, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:5, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:8, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:9, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:10, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:introduction:11

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Common uses

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Biological role

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What evidence has studied

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Potential benefits studied

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Safety considerations

A frozen NIH ODS source explicitly identifies this ingredient or form. Source wording is preserved without creating a new conclusion.

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Structural characterization

Evidence profile

No overall rating assigned

Evidence source: NIH ODS evidence synthesis
Linked references: 5 identified
Human evidence: Human evidence identified
Randomized trials: Randomized trial identified
Reviews and meta-analyses: Systematic reviews or meta-analyses not identified in the frozen metadata
Evidence recency: 2005–2020
Source-described consistency: Not characterized in these source blocks
MEDucated evidence rating: Not assigned

Reference counts describe frozen source associations; a larger count does not establish stronger evidence.

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Evidence types identified

Government reference1
Study type could not be determined2
Randomized controlled trial1
Regulatory source1

Source-described limitations

No explicit limitation phrase was identified in these imported source blocks.

Classified references

Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington, DC: National Academy Press; 2005.
Government reference · Population basis: unknown · Directness: not assessed
Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Nicholls SJ, Lincoff M, Garcia M, Dash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk. The STRENGTH randomized clinical trial. JAMA 2020;324:2268-80. [PubMed abstract]
Randomized controlled trial · Population basis: human · Directness: not assessed
EFSA Panel on Dietetic Products NaA. Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA Journal 2012;10:2815.
Study type could not be determined · Population basis: unknown · Directness: not assessed
U.S. Food and Drug Administration. Qualified health claims: letters of enforcement discretion. 2019.
Regulatory source · Population basis: unknown · Directness: not assessed

For most macronutrients, the IOM has established an acceptable macronutrient distribution range (AMDR) that suggests an acceptable range of intake. The AMDR for total fat intake, for example, is based on adverse effects from either very low fat or very high fat diets. The IOM established an AMDR for omega-3s (as ALA) of 0.6% to 1.2% of energy for children and adults age 1 year and older [5]. The IOM also noted that about 10% of the AMDR can be consumed as EPA and/or DHA.

The IOM did not establish a UL for any omega-3s, although it noted that high doses of DHA and/or EPA (900 mg/day of EPA plus 600 mg/day DHA or more for several weeks) might reduce immune function due to suppression of inflammatory responses. Doses of 2–15 g/day EPA and/or DHA might also increase bleeding time by reducing platelet aggregation [5]. However, according to the European Food Safety Authority, long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe [195]. It noted that these doses have not been shown to cause bleeding problems or affect immune function, glucose homeostasis, or lipid peroxidation. Similarly, FDA has concluded that dietary supplements providing no more than 5 g/day EPA and DHA are safe when used as recommended [196]. Two large clinical trials completed after these assessments found that taking 4 g/day of omega-3 supplements for several years slightly increased the risk of atrial fibrillation in people with CVD or at high risk of CVD [63,64].

Where did MEDucated get this?

Omega-3 Fatty Acids

Publisher: NIH Office of Dietary Supplements
Revision: August 22, 2025
Source fingerprint: 80b4434afaf71303420a09ab193258a2d656c3bdec58a108fe3d14961d1bb750
Source blocks: ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:safety-of-omega-3s:1, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:safety-of-omega-3s:2

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Forms and chemical variants

A frozen NIH ODS source explicitly identifies this ingredient or form. Source wording is preserved without creating a new conclusion.

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Structural characterization

Evidence profile

No overall rating assigned

Evidence source: NIH ODS evidence synthesis
Linked references: 7 identified
Human evidence: Human evidence identified
Randomized trials: Randomized trials not identified in the frozen metadata
Reviews and meta-analyses: Systematic reviews or meta-analyses not identified in the frozen metadata
Evidence recency: 2008–2016
Source-described consistency: Not characterized in these source blocks
MEDucated evidence rating: Not assigned

Reference counts describe frozen source associations; a larger count does not establish stronger evidence.

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Evidence types identified

Study type could not be determined6
Regulatory source1

Source-described limitations

No explicit limitation phrase was identified in these imported source blocks.

Classified references

National Institutes of Health. Dietary Supplement Label Database. 2015.
Study type could not be determined · Population basis: unknown · Directness: not assessed
U.S. Food and Drug Administration. Fish: what pregnant women and parents should know. 2014.
Regulatory source · Population basis: human · Directness: not assessed
ConsumerLab.com. Product review: fish oil and omega-3 fatty acid supplements review (including krill, algae, calamari, green-lipped mussel oil). 2016.
Study type could not be determined · Population basis: unknown · Directness: not assessed
Dyerberg J, Madsen P, Moller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids 2010;83:137-41. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Cunningham E. Are krill oil supplements a better source of n-3 fatty acids than fish oil supplements? J Acad Nutr Diet 2012;112:344. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Davidson MH, Kling D, Maki KC. Novel developments in omega-3 fatty acid-based strategies. Curr Opin Lipidol 2011;22:437-44. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed
Arterburn LM, Oken HA, Bailey Hall E, Hamersley J, Kuratko CN, Hoffman JP. Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid. J Am Diet Assoc 2008;108:1204-9. [PubMed abstract]
Study type could not be determined · Population basis: unknown · Directness: not assessed

Read imported source wording

LC omega-3s are present in several dietary supplement formulations, including fish oil, krill oil, cod liver oil, and vegetarian products that contain algal oil. A typical fish oil supplement provides about 1,000 mg fish oil, containing 180 mg EPA and 120 mg DHA, but doses vary widely [30]. Cod liver oil supplements provide vitamin A and vitamin D in addition to LC omega-3s. Although seafood contains varying levels of methyl mercury (a toxic heavy metal) [31], omega-3 supplements have not been found to contain this contaminant because it is removed during processing and purification [32].

Dietary supplements can contain several different forms of omega-3s, including natural triglycerides, free fatty acids, ethyl esters, re-esterified triglycerides, and phospholipids [32-34]. Natural triglycerides are the form that occur naturally in fish oil, whereas ethyl esters are synthesized from natural triglycerides by replacement of the glycerol molecule of the triglyceride with ethanol. Re-esterified triglycerides are formed by the conversion of ethyl esters back to triglycerides. Omega-3s as re-esterified triglycerides, natural triglycerides, and free fatty acids have somewhat higher bioavailability than ethyl esters, but consumption of all forms significantly increases plasma EPA and DHA levels [33,35].

Plant-based sources of omega-3s from algal oil usually provide around 100–300 mg DHA; some contain EPA as well. These supplements typically contain omega-3s in the triglyceride form [32]. According to a small study, the bioavailability of DHA from algal oil is equivalent to that from cooked salmon [43].

Where did MEDucated get this?

Omega-3 Fatty Acids

Publisher: NIH Office of Dietary Supplements
Revision: August 22, 2025
Source fingerprint: 80b4434afaf71303420a09ab193258a2d656c3bdec58a108fe3d14961d1bb750
Source blocks: ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:dietary-supplements:1, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:dietary-supplements:2, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:dietary-supplements:4

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Intake and dose reference information

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Structural characterization

Evidence profile

No overall rating assigned

Evidence source: NIH ODS evidence synthesis
Linked references: 0 identified
Human evidence: Human evidence not identified in the frozen metadata
Randomized trials: Randomized trials not identified in the frozen metadata
Reviews and meta-analyses: Systematic reviews or meta-analyses not identified in the frozen metadata
Evidence recency: Reference years not identified
Source-described consistency: Not characterized in these source blocks
MEDucated evidence rating: Not assigned

Reference counts describe frozen source associations; a larger count does not establish stronger evidence.

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Evidence types identified

Study type could not be determined from linked frozen metadata.

Source-described limitations

No explicit limitation phrase was identified in these imported source blocks.

Classified references

No linked reference metadata was identified for these source blocks.

Read imported source wording

Table 1 lists the current AIs for omega-3s in grams per day. Human milk contains omega-3s as ALA, EPA, and DHA, so the IOM established an AI for infants from birth to 12 months that is equivalent to the mean intake of omega-3s in healthy, breastfed infants.

For infants, the AIs apply to total omega-3s. For age 1 and older, the AIs apply only to ALA because ALA is the only omega-3 that is essential. The IOM did not establish specific intake recommendations for EPA, DHA, or other LC omega-3s.

Where did MEDucated get this?

Omega-3 Fatty Acids

Publisher: NIH Office of Dietary Supplements
Revision: August 22, 2025
Source fingerprint: 80b4434afaf71303420a09ab193258a2d656c3bdec58a108fe3d14961d1bb750
Source blocks: ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:recommended-intakes:4, ingredient-block:epa:ods-block:omega-3-fatty-acids-health-professional:recommended-intakes:5

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Populations needing caution

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Pregnancy and lactation

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Laboratory and test considerations

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Regulatory status

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Architecture readiness

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