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Eicosapentaenoic (EPA) and Docosahexaenoic Acid (DHA)

What are eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)?

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are nonessential long-chain polyunsaturated omega-3 fatty acids, which can be produced in the human body from alpha-linolenic acid, but under certain conditions, for example, in preterm infants, their production may be insufficient. In the human body, DHA can be produced from EPA and, to a lesser extent, EPA can be produced from DHA [3]. Foods rich in EPA and DHA include certain oily fish (see Chart 1). In fish, EPA and DHA are bound to glycerol, so they are in the form of triglycerides [4].

Chart 1. Foods High in EPA and DHA

FOOD EPA (g) DHA (g) Amount providing
1 g EPA + DHA
Mackerel, Pacific (3 oz, 85 g) 0.6 1 1.5 oz
Salmon, chinook (3 oz, 85 g) 0.9 0.6 2 oz
Salmon, coho, cooked (3 oz, 85 g) 0.5 0.7 3 oz
Salmon, sockeye (3 oz, 85 g) 0.5 0.6 3 oz
Salmon, chum, canned (3 oz, 85 g) 0.4 0.6 3 oz
Oysters, Pacific (3 oz, 85 g) 0.7 0.3 3 oz
Halibut, Greenland (3 oz, 85 g) 0.6 0.4 3 oz
Sardines, Pacific, canned (3 oz, 85 g) 0.5 0.7 3 oz
Trout, rainbow, wild (3 oz, 85 g) 0.4 0.4 3.5 oz

Chart 1. lists foods high in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [20,21] and low in sodium [22], mercury [23,33] and PCBs [24,33]

EPA + DHA Supplements

EPA and DHA supplements without prescription (over-the-counter):

  • Fish oils containing EPA and DHA are extracted from the tissues of oily fish, such as sardines, anchovies, herring or salmon.
  • Cod liver oil is high in EPA and DHA, and also in vitamins A and D.
  • Krill oil contains EPA, DHA, phosphatidylcholine (“marine lecithin”), folic acid and vitamin A. It is extracted from shrimp-like marine crustaceans of order Euphausiacea [5]. Krill oil is Generally Recognized As Safe (GRAS) by the U.S. Food and Drug Administration (FDA) [5].
  • DHA-rich oil from the microalgae Crypthecodinium cohnii [9].
  • Glycerol esters of EPA and DHA are compounds of glycerol and three fatty acids, one of which is either EPA or DHA; they also naturally occur in fish [4].

Prescription EPA and DHA supplements:

  • Ethyl esters of EPA and DHA (ethyl-EPA or EPA EE and ethyl-DHA or DHA EE) are semi-synthetic compounds of ethanol and three fatty acids, from which at least two are either EPA or DHA, so ethyl esters are more concentrated source of EPA + DHA than glycerol esters [10]. Ethyl esters are available as prescription drugs for hypertriglyceridemia in the U.S. and EU, or as nonprescription dietary supplements elsewhere.
  • Methyl esters of EPA and DHA (methyl-EPA or EPA ME and methyl-DHA or DHA ME)

Some, but not all, studies have shown that free omega-3 fatty acids from fish oil or omega-3 triglycerides from fish are better absorbed than omega-3 ethyl esters [4]. One study has shown that methyl esters of EPA and DHA are equally effective in lowering triglycerides than glycerol esters and they may both increase LDL cholesterol [11].

EPA and DHA or Fish Oil Benefits

Consumption of fish, which are high in EPA and DHA, at least once to twice weekly, or taking fish oil (EPA + DHA) supplements is PROBABLY EFFECTIVE for [1,12]:

  • Decreasing the risk of coronary heart disease
  • Lowering the blood triglycerides (but not total or LDL cholesterol) [7,8]
  • Fish oil may slightly decrease joint stiffness and pain in rheumatoid arthritis [6]; it may take at least 12 weeks for supplements to take effect.
  • In one small trial, fish oil has prevented symptoms of salicylate intolerance [15].

NOTE 1: Consumption of oily fish high in omega-3 fatty acids can decrease the risk of chronic heart disease in people with known risk factors of chronic heart disease (obesity, genetic predisposition, high blood triglycerides and LDL cholesterol), but less likely in people without known risk factors [16].

NOTE 2: Fish oil may have no additional heart-protective benefit for those who regularly eat fish high in omega-3 fatty acids.

There is SOME EVIDENCE that fish oil supplements (3 g/day for a week) can decrease delayed onset muscle soreness (DOMS) after exercise [36,37,38,39]. In some studies, fish oil did not reduce DOMS, though [40,41].

Omega-3 supplements probably have NO EFFECT on glucose tolerance (no effect on HgbA1c, the indicator of the long-term glucose levels) [13].

There is INSUFFICIENT EVIDENCE about the effectiveness of omega-3 fatty acids supplements (fish oil) in prevention or treatment of abnormal heart rhythms, age-related macular degeneration (AMD) [17], Alzheimer’s disease, angina pectoris (heart-related chest pain), asthma, atherosclerosis, autism, bipolar disorder, cancer (colorectal, breast, prostate), Crohn’s disease (inflammatory bowel disease), cystic fibrosis, depression, diabetes mellitus type 2 (insulin resistance) [19,35], eczema, epilepsy, fatigue, high blood pressure [13], high cholesterol, IgA nephropathy, kidney stones, menstrual pain, migraine, movement disorders (Tardive dyskinesia), multiple sclerosis, nephrotic syndrome, nerve pain, osteoarthritis, osteoporosis, painful menstruation, pancreatitis, psoriasis, Raynaud’s disease, schizophrenia, sickle cell disease, stroke, systemic lupus erythematosus (SLE), thrombosis, transplant rejection, ulcerative colitis or weight loss in cancer, or in enhancing immunity, sun protection, visual acuity, wound healing, or brain development in infants [12,18].

EPA and DHA Safety: Side Effects, Toxicity

Side effects of fish oil supplements may include fishy aftertaste and odor, belching, heartburn, nausea, diarrhea, constipation; doses greater than 3 g/day may increase the risk of bleeding [1]. Besides that, ethyl esters of DPA and DHA may cause jaw, arm or back pain or irregular heart beat [10]. Allergic reactions may include sweating, flushing, rash, chest pain, nausea, diarrhea.

Regular consumption of cod liver oil may lead to excessive intake of vitamins A, D or E [31]. No serious side effects of fish oil during pregnancy or breastfeeding have been reported.

Fish oil and cod liver oil supplements usually do not contain toxic amounts of mercury or other toxins [32].

Who should avoid omega-3 foods or supplements [31]?

  • Individuals allergic to fish
  • Pregnant and breastfeeding women, infants and small children should avoid fish high in mercury (see below).
  • Children, pregnant and breastfeeding women, anyone with diabetes or taking contraceptive pills, blood thinners, beta-blockers, diuretics or other drugs should speak with a doctor before taking omega-3 supplements.

Mercury and Other Contaminants in Fish

Mercury is toxic for the brain and kidneys, especially for the fetus, infants and young children. The U.S. Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) recommend pregnant women and those who may become pregnant in a year, breastfeeding women and young children to avoid eating fish high in mercury (Chart 2) [26].

PCBs (polychlorinated biphenyls) are toxic industrial chemicals, which are known animal carcinogens and are considered probable carcinogens for human [27].

In general, farmed fish, especially European fish, such as farmed Atlantic salmon tend to be high in contaminants (mercury, dioxin and PCBs from grounded fish used as feed, but also antibiotics, pesticides, growth hormone) [28]. Sea areas arranged by concentration of mercury and other contaminants (from highest to lowest): The Gulf of Mexico > Mediterranean > Atlantic > Pacific [29].

The current Food and Drug Administration (FDA) safety limit for methyl mercury in fish is 1 ppm (parts per million), and for PCBs 2 ppm [30], but the limit of Environmental Protection Agency (EPA) for PCBs is much lower: 0.4 ppm.

To reduce the toxin exposure, remove the skin and under-skin fat from fish, and prepare them by grilling or broiling rather than frying [27].

Chart 2. Fish High in Mercury and PCBs

FISH Mercury ppm (max) [23] PCBs [24,34]
Shark 4.5
Tilefish (Gulf of Mexico) 3.7
Swordfish 3.2
Bass, Chilean 2.2
Barramundi PubMedBetterhealth
Tuna, fresh 1.8 High
Mackerel, Spanish or king 1.7
Halibut 1.5
Bluefish 1.5 High
Snapper 1.4
Grouper, all species 1.2
Orange roughy 1.1
Sablefish 1
Cod 1
Bowflin 1
Bass, saltwater, black, striped 1 Moderate
Tuna, canned, light or albacore 0.9 High
Marlin 0.9 (methylmercury)
Pollock 0.8
Sea trout (weakfish) 0.7 High
Trout, freshwater 0.7
Crab 0.6
Chain pickerel 0.6
Herring 0.6 High
Tilefish, Atlantic 0.5
Walleye ? High
Eel, American or European ? High
Croaker, white, Atlantic ? High
Flounder, summer or winter ? High
Sturgeon, wild ? High
Perch, yellow ? High
Salmon, farmed or Atlantic ?  High

Chart 2 references: [23,24,34,35]

  1. Essential fatty acids  Linus Pauling Institute
  2. Letter Regarding Eggs with Enhanced Omega-3 Fatty Acid Content and a Balanced 1:1 Ratio of Omega-3/Omega-6 Fatty Acids and Reduced Risk of Heart Disease and Sudden Fatal Heart Attack  US Food and Drug Administration
  4. Siri-Tarino PW et al, 2010, Saturated Fatty Acids and Risk of Coronary Heart Disease: Modulation by Replacement Nutrients  PubMed Central
  5. 2010, Notification of GRAS Determination for Krill Oil  US Food and Drug Administration
  6. Miles EA et al, 2012, Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis  PubMed
  7. Schwab U et al, 2014, Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review  PubMed Central
  8. Bunea R et al, 2004, Evaluation of the Effects of Neptune Krill Oil on the Clinical Course of Hyperlipidemia  Alternative Medicine Review
  9. Doughman SD et al, 2007, Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA  PubMed
  10. Lovaza  Drugs.com
  11. Harris WS et al, 1988, Omega-3 fatty acids in hypertriglyceridemic patients: triglycerides vs methyl esters,   PubMed
  12. Omega-3 fatty acids, fish oil, alpha-linolenic acid, evidence  Mayo Clinic
  13. 2004, Effects of Omega-3 Fatty Acids on Cardiovascular Risk Factors and Intermediate Markers of Cardiovascular Disease  Agency for Healthcare Research and Quality
  14. Which fish are healthy to eat?  The Food Coach
  15. Healy E et al, 2008, Control of salicylate intolerance with fish oils  PubMed
  16. Kris-Etherton PM et al, 2002, Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease  Circulation
  17. Hodge WG et al, 2006, Efficacy of omega-3 fatty acids in preventing age-related macular degeneration: a systematic review  PubMed
  18. 2005, Omega-3 Fatty Acids and Health National Institute of Health, Office of Dietary Supplements
  19. Risérus U et al, 2009, Dietary fats and prevention of type 2 diabetes  PubMed
  20. List of foods high in EPA US Department of Agriculture
  21. List of foods high in DHA US Department of Agriculture
  22. List of foods high in sodium US Department of Agriculture
  23. Mercury Levels in Commercial Fish and Shellfish (1990-2010)  US Food and Drug Administration
  24. 2008, Health fish, healthy families  Association of Reproductive Health Professionals
  25. D’hooghe MB et al, 2012, Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis  Wiley Online Library
  26. 2014, Fish: What Pregnant Women and Parents Should Know  US Food and Drug Administration
  27. 2012, Public Health Implications of Exposure to Polychlorinated Biphenyls (PCBs)  Environmental Protection Agency
  28. Hites RA et al, 2004, Global Assessment of Organic Contaminants in Farmed Salmon  Science
  29. Sunderland EM et al, 2006, Mercury Exposure from Domestic and Imported Estuarine and Marine Fish in the U.S. Seafood Market  PubMed Central
  30. FDA and EPA Safety Levels in Regulations and Guidance  The US Food and Drug Administration
  31. Omega-3 fatty acids, fish oil, alpha-linolenic acid, safety  Mayo Clinic
  32. Smutna M et al, 2009, Fish oil and cod liver as safe and healthy food supplements  PubMed
  33. Seafood health alerts Environmental Defense Fund
  34. 1999, Polychlorinated Biphenyls (PCBs) Update: Impact on Fish Advisories  Environmental Protection Agency
  35. Wu JH et al, 2012, Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis  PubMed
  36. Tartibian B et al, 2009, The effects of ingestion of omega-3 fatty acids on perceived pain and external symptoms of delayed onset muscle soreness in untrained men  PubMed
  37. Jouris KB et al, 2011, The Effect of Omega-3 Fatty Acid Supplementation on the Inflammatory Response to eccentric strength exercise  PubMed Central
  38. Lembke P et al, Influence of Omega-3 (N3) Index on Performance and Wellbeing in Young Adults after Heavy Eccentric Exercise  PubMed Central
  39. Baum K et al, 2013, Marine oil dietary supplementation reduces delayed onset muscle soreness after a 30 km run  PubMed Central
  40. Gray P et al, 2014, Fish oil supplementation reduces markers of oxidative stress but not muscle soreness after eccentric exercise.
  41. Lenn J et al, 2002, The effects of fish oil and isoflavones on delayed onset muscle soreness  PubMed

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