Health Care Professional Information

Brand Name

Omegaven®, Max-EPA

Clinical Summary

A type of polyunsaturated fatty acid (PUFA) derived mainly from fish oil, omega-3 fatty acids are used as dietary supplement for depression, to lower cholesterol, and to reduce the risk of heart attack. A large survey of Finnish adults found that depressive symptoms were significantly higher among infrequent fish consumers (1) and other studies have shown that individuals with major depression have marked depletions in omega-3 fatty acids (2). However, omega-3 fatty acid supplementation did not relieve depression in adults with major depression (3), mild to moderate depression (4), or perinatal depression (5), and yielded mixed results in those with schizophrenia (23). But data from a randomized trial suggest that omega-3 may be useful in reducing the risk of progression to psychiatric disorders and as a safe preventive measure in young adults at a risk for psychotic conditions (35).

Supplementation with docosahexaenoic acid (DHA) improved learning and memory function in age related cognitive decline (41). However, consumption of fish oil during pregnancy does not improve cognitive or language outcomes in newborns (37) and does not improve intelligence of the kids (42).
Studies of omega-3 fatty acid supplementation and cognition in young children (6) and elderly subjects (7) are inconclusive.

Omega-3 fatty acid supplementation lowers cholesterol (8) (33) and may reduce recurrence in patients with history of stroke (32). However, it does not lower the risk of cardiovascular disease events (9). Omega-3 may help patients with ulcerative colitis (10), but was ineffective in the treatment of Crohn's disease (13). In adults with rheumatoid arthritis, reduction in NSAID use was reported after omega-3 fatty acid supplementation (14); Omega-3 may also be effective in reducing NSAID-associated gastroduodenal damage (47). Other studies indicate that omega-3 may lower the magnitude of the body's inflammatory response (18), and can reduce sensitivity to sunburn(20) and to ultraviolet radiation (44). Reviews of trials using omega-3 fatty acids have shown possible benefits for patients with cystic fibrosis (21), but no benefit in those with asthma (22). Dietary supplementation with fish oil may help reduce the symptoms of systemic lupus erythematosus (24).
Findings of a systematic review support benefits of polyunsaturated omega-3 fatty acid consumption on insulin sensitivity and adipocyte function (45).

Data on omega-3 fatty acid supplementation for cancer prevention are inconclusive. It may reduce colon cancer risk (11) and improve immune response in patients undergoing colorectal cancer resection (12), but did not affect cancer outcomes (15) (43) although data from a prospective study suggest its association with reduced occurrence of renal cell carcinoma in women (16). Fish oil supplementation may lower the risk of breast cancer (36). However, high blood concentration of omega-3 is associated with increased risk of prostate cancer (17). Further studies are needed.
Preliminary findings suggest benefits of fish oil supplementation in increasing efficacy of chemotherapy, improving survival (38), and for maintenance of weight and muscle mass (39) in patients with nonsmall cell lung cancer (NSCLC). An eicosapentanoic acid (EPA)-enriched oral supplement improved tolerability of chemotherapy in patients with advanced colorectal cancer (40).

Omega-3 fatty acids are thought to have anticoagulant effects. But studies show that they do not affect coagulation or platelet function after surgery (19).

Food Sources
Purported Uses
  • Asthma
  • Atherosclerosis
  • Cancer prevention
  • Cardiovascular disease
  • Colitis
  • Cystic fibrosis
  • Depression
  • High cholesterol
  • Schizophrenia

Fatty Acids: Eicosapentanoic (EPA), Docosahexanoic (DHA), Myristic, Palmitic, Palmitoleic, Stearic, Oleic, Linoleic, Linolenic, Stearidonic, Eicosanoic, Arachidonic, Docosanoic and docosapentanoic (DPA) (19)

Mechanism of Action

Omega-3 fatty acids are polyunsaturated fatty acids containing two or more double bonds in their acyl chain and a double bond on carbon number (3) (26). Changes in omega-3 fatty acid blood levels have been associated with cardiovascular disease and depression (27). The cardioprotective effects of omega-3 fatty acids likely are due its ability to be incorporated into and thereby enhance the stability of atherosclerotic plaques (26). Increasing the intake of polyunsaturated fatty acids has been shown to increase lipid peroxidation. Supplementation with omega-3 fatty acids, therefore, may increase the oxidative stress on the body. Studies have shown that mucosal alpha-tocopherol levels decrease upon omega-3 fatty acid supplementation, which researchers believe may result from the body's attempt to counteract the added oxidative burden (11). Besides reducing serum anti-oxidant levels, little is known about how this added oxidative stress affects the body.

Omega-3 fatty acid supplementation has been shown to decrease IL-6 (18) and tumor necrosis factor-alpha (28) levels while leaving most other mononuclear cell functions unaffected (29). Omega-3 fatty acids may also reduce inflammation in patients with ulcerative colitis by reducing rectal dialysate leukotriene B4 (10). Because of their anti-inflammatory effects, omega-3 fatty acids were thought to benefit patients with asthma (22) and cystic fibrosis (21); however, data are inconclusive.
Increasing PUFA intake in pregnant women increases PUFA concentration but not cytokine concentration in human milk (30).

Omega-3 fatty acid supplementation provides protection against ultra-violet radiation-induced erythema and p53 expression, a biomarker of DNA damage (20).

Adverse Reactions

Fishy aftertaste (11), loose stools and nausea (31) have been reported following intake of large doses of omega-3 fatty acids.

Herb-Drug Interactions
  • Nonsteroidal Anti-inflammatory drugs (NSAIDS): Fish oil can have additive anticoagulant/antiplatelet effects (34).
  • Glucocorticoids: Omega-3 supplementation may potentiate some of the adverse effects of glucocorticoids (46).
Herb Lab Interactions
  • May reduce levels of alpha-tocopherol and beta-carotene (11) (28).
  • High levels of omega-3 fatty acids may decrease triglyceride and increase LDL cholesterol levels (9).
  • Doses higher than 3 grams per day may increase bleeding time (25).
Literature Summary and Critique

Tanaka K, et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke. 2008;39(7):2052-2058.
The JELIS trial was a large, prospective, clinical-controlled trial of 18,645 hypercholesterolemic patients that received statin therapy with or without omega-3 fatty acid supplementation (1800 mg/day). While stroke incidence during the 4.6 year mean follow-up period was not affected by omega-3 fatty acid supplementation in patients without a history of stroke, stroke recurrence was significantly reduced in individuals with a history of stroke. Due to the open-label design of this study, further studies are required.

Duffy EM et al. The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. J. Rheumatology. 2004;31(8):1551-6.
A double blind, double placebo controlled trial. Fifty-two SLE patients were randomly assigned to 4 treatment groups that received 3 g fish oil and 3 g of copper, 3 g fish oil and placebo copper, 3 g copper and 3 g placebo fish oil, or both placebo capsules. Researchers found a significant reduction in symptoms of SLE in patients who took fish oil capsules compared to those on placebo. There was no measurable effect on symptoms in patients who took copper. Larger trials are needed to support this claim.

Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 2003;361:477-85.
A randomized controlled trial of polyunsaturated fatty acids and stability of atherosclerotic plaques. 188 patients awaiting carotid endarterectomy were randomized to receive sunflower oil (high omega-6 concentration), fish oil (high omega-3 concentration) or control oil until surgery. Each patient consumed six capsules per day each containing 1 g of oil and 1 mg alpha-tocopherol. Duration of treatment ranged from seven to 189 days with a median of 42 days. Patients receiving the fish oil supplementation were found to have readily incorporated omega-3 polyunsaturated fatty acids in their atherosclerotic plaques thereby enhancing the stability of the plaques. Patients receiving either sunflower oil or control had no change in fatty-acid composition or atherosclerotic stability during the course of treatment. Researchers believe that this stability of plaques may explain the reductions in cardiovascular events associated with omega-3 polyunsaturated fatty acid intake.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
  1. Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamaki H et al. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr.Serv. 2001;52:529-31.
  2. Mischoulon D,.Fava M. Docosahexanoic acid and omega-3 fatty acids in depression. Psychiatr. Clin North Am 2000;23:785-94.
  3. Grenyer BF, Crowe T, Meyer B, et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2007 Oct 1;31(7):1393-6.
  4. Rogers PJ, Appleton KM, Kessler D, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr. 2008 Feb;99(2):421-31.
  5. Rees AM, Austin MP, Parker GB. Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry. 2008 Mar;42(3):199-205
  6. Ryan AS, Nelson EB. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr (Phila) 2008 May;47(4):355-62.
  7. van de Rest O, Geleijnse JM, Kok FJ, et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 2008 Aug 5;71(6):430-8.
  8. Kabir M, Skurnik G, Naour N, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 2007 Dec;86(6):1670-9.
  9. Rizos E, Ntzani E, Bika E, et al. Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-analysis. JAMA. 2012;308(10):1024-1033.
  10. Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL et al. Dietary supplementation with fish oil in ulcerative colitis. Ann.Intern.Med 1992;116:609-14.
  11. Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P et al. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 1994;107:1709-18.
  12. Liang B, Wang S, Ye YJ, et al. Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. World J Gastroenterol. 2008;14(15):2434-9
  13. Feagan BG, Sandborn WJ, Mittmann U, et al. Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA 2008 Apr 9;299(14):1690-7.
  14. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford) 2008 May;47(5):665-9.
  15. MacLean CH, et al. Effects of Omega-3 Fatty Acids on Cancer Risk. JAMA 2006; 295(4).
  16. Wolk A, Larsson SC, Johansson J, Ekman P. Long-term fatty fish consumption and renal cell carcinoma incidence in women. JAMA 2006;296(11):1371-1376.
  17. Brasky TM, Darke AK, Song X, et al. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst. 2013 Aug 7;105(15):1132-41.
  18. Weiss G, Meyer F, Matthies B, Pross M, Koenig W, Lippert H. Immunomodulation by perioperative administration of n-3 fatty acids. Br J Nutr 2002;87 Suppl 1:S89-S94.
  19. Heller AR, Fischer S, Rossel T, Geiger S, Siegert G, Ragaller M et al. Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery. Br J Nutr 2002;87 Suppl 1:S95-101.
  20. Rhodes LE, Shahbakhti H, Azurdia RM, Moison RM, Steenwinkel MJ, Homburg MI et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis 2003;24:919-25.
  21. Beckles WN, Elliott TM, Everard ML. Omega-3 fatty acids (from fish oils) for cystic fibrosis. Cochrane.Database.Syst.Rev. 2002;CD002201.
  22. Woods RK, Thien FC, Abramson MJ. Dietary marine fatty acids (fish oil) for asthma in adults and children. Cochrane.Database.Syst.Rev. 2002;CD001283.
  23. Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane.Database.Syst.Rev. 2003;CD001257.
  24. Duffy EM, et al. The Clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. J. Rheumatology 2004;31(8):1551-6.
  25. Lewis, C. J. Letter Regarding Dietary Supplement Health Claim for Omega-3 Fatty Acids and Coronary Heart Disease. FDA Docket No. 91N-0103. 10-31-2000. Accessed July 25, 2014.
  26. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 2003;361:477-85.
  27. Severus WE, Littman AB, Stoll AL. Omega-3 fatty acids, homocysteine, and the increased risk of cardiovascular mortality in major depressive disorder. Harv.Rev.Psychiatry 2001;9:280-93.
  28. Holm T, Berge RK, Andreassen AK, Ueland T, Kjekshus J, Simonsen S et al. Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients. Transplantation 2001;72:706-11.
  29. Wallace FA, Miles EA, Calder PC. Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Br J Nutr 2003;89:679-89.
  30. Hawkes JS, Bryan DL, Makrides M, Neumann MA, Gibson RA. A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. Am J Clin Nutr 2002;75:754-60.
  31. Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom.Med 1999;61:712-28.
  32. Tanaka K, Ishikawa Y, Yokoyama M, et al. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke. 2008 Jul;39(7):2052-8.
  33. Gunnarsdottir I, Tomasson H, Kiely M, et al. Inclusion of fish or fish oil in weight-loss diets for young adults: effects on blood lipids. Int J Obes. 2008;32(7):1105-12.
  34. Haller C, Kearney T, Bent S, et al. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. 2008 Jun;4(2):84-92.
  35. Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-Chain {omega}-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54.
  36. Brasky TM, Lampe JW, Potter JD, Patterson RE, White E. Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort. Cancer Epidemiol Biomarkers Prev. 2010;19(7); 1696-708.
  37. Makrides M, Gibson R,McPhee A, et al. Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children. A Randomized Controlled Trial. JAMA. 2010;304(15):1675-1683.
  38. Murphy RA, Mourtzakis M, Chu QS, et al. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117(16):3774-80.
  39. Murphy RA, Mourtzakis M, Chu QS, et al. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011 Apr 15;117(8):1775-82.
  40. Trabal J, Leyes P, Forga M, Maurel J. Potential usefulness of an EPA-enriched nutritional supplement on chemotherapy tolerability in cancer patients without overt malnutrition. Nutr Hosp. 2010 Sep-Oct;25(5):736-40.
  41. Sinn N, Milte CM, Street SJ, et al. Br J Nutr. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr. 2011 Sep 20:1-12.
  42. Campoy C, Escolano-Margarit MV, Ramos R, et la. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. Am J Clin Nutr. 2011; 94(6 Suppl):1880S-1888S.
  43. Andreeva VA, Touvier M, Kesse-Guyot E, Julia C, Galan P, Hercberg S. B vitamin and/or ω-3 fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or omega-3 fatty acids (SU.FOL.OM3) randomized trial. Arch Intern Med 2012 Apr 9;172(7):540-7.
  44. Pilkington SM, Massey KA, Bennett SP, et al. Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses. Am J Clin Nutr. 2013 Mar;97(3):646-52.
  45. Wu JH, Cahill LE, Mozaffarian D. Effect of Fish Oil on Circulating Adiponectin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2013 Jun;98(6):2451-9.
  46. Fappi A, Godoy TS, Maximino JR, et al. The effects of omega-3 Fatty Acid supplementation on dexamethasone-induced muscle atrophy. Biomed Res Int. 2014;2014:961438.
  47. Park JM, Han YM, Jeong M, et al. Omega-3 polyunsaturated acids as an angelus custos to rescue patients from NSAID-induced gastroduodenal damage. J Gastroenterol. 2015 Jan 13. [Epub ahead of print]

Consumer Information

How It Works

Bottom Line: Omega-3 fatty acids have not been shown to prevent cancer.

Omega-3 fatty acids are obtained from fish oil. They have been used to protect against cardiovascular events such as heart attack. Studies have shown that omega-3 fatty acids can be taken up by the fatty deposits that line the arteries, thereby improving the stability of those deposits. Omega-3 fatty acids do not seem to affect the clotting of blood. Omega-3 fatty acids may reduce inflammation by decreasing some of the signals that cells send to each other. It is thought that patients with colitis, asthma, cystic fibrosis and those before surgery may benefit from this reduced inflammatory effect. Omega-3 fatty acid supplements have been shown to be absorbed by the skin and protect it against ultra-violet radiation damage.
Omega-3 fatty acid may reduce the risk of breast cancer, but may increase the risk of prostate cancer.

Purported Uses
  • To treat asthma
    A review of published trials shows no effect of omega-3 on asthma.
  • To treat fatty deposits on the inside of arteries (atherosclerosis)
    Studies have shown that omega-3 can increase the stability of these deposits, which may make them less dangerous.
  • To protect against cardiovascular disease
    Studies have shown that omega-3 can reduce the frequency and severity of cardiovascular events such as heart attacks.
  • To improve the symptoms of colitis
    Studies have shown that omega-3 may improve the symptoms associated with colitis.
  • To alleviate the symptoms associated with cystic fibrosis
    One study showed an improvement in breathing parameters for patients taking omega-3 supplements, however other trials have shown no benefit. Larger studies are necessary to determine the actual effect.
  • To alleviate depression
    A study of a few thousand people in Finland found that people who ate less fish were more likely to have the symptoms of depression than those who ate more fish. Other studies have also shown a connection between omega-3 levels and depression scores, however few studies have attempted to determine if omega-3 supplementation affects depression symptoms.
  • To lower cholesterol levels
    A review of published trials of omega-3 for lowering cholesterol levels in patients with diabetes found that while omega-3 lowered triglyceride levels, it also raised LDL cholesterol levels.
  • To treat psychiatric disorders
    A recent study showed that omega-3 may be useful in reducing the risk of progression to psychiatric disorders.
  • To protect the skin against ultra-violet radiation damage.
    Studies have shown omega-3 to be incorporated into the skin and offer protection against UV damage which may reduce cancer risk.
  • To prevent cancer
    Omega-3 fatty acid may reduce the risk of breast cancer, but may increase the risk of prostate cancer.
Research Evidence

Heart Disease
People who consume more omega-3 fatty acid supplementation have been shown to have fewer and less severe cardiovascular events such as heart attacks. One hundred and eighty-eight patients awaiting endarterectomy (the surgical removal of the inner lining of a clogged artery) took part in a trial to determine how omega-3 produces these effects. Patients were randomized to receive either fish oil, which is high in omega-3 fatty acids, sunflower oil, which is high in a different kind of fatty acids or a control, which contained the same proportion of fatty acids that people typically eat on a daily basis. Patients consumed 6 grams of oil and 6 milligrams of alpha-tocopherol, an antioxidant, per day for an average duration of 42 days. Patients who consumed the fish oil were found to have incorporated the omega-3 fatty acids into the plaques on their arteries which enhanced the stability of these plaques. Patients receiving sunflower oil or the control oil did not experience a change in their plaques. Researchers believe that increasing the stability of the plaques on the walls of the arteries reduces the chances that some of the plaque will break off and lead to a heart attack. It appears that this phenomenon explains why omega-3 may help protect against heart attacks.

Systemic Lupus Erythematosus
Fifty two patients participated in a recent clinical trial performed to assess the beneficial effects of dietary supplementation with omega-3 fish oils and copper. Patients were randomly assigned to receive fish oil and placebo copper, fish oil and copper, copper and placebo fish oil, and the last group received both placebo capsules. Researchers found a reduction in symptoms of SLE in patients who took fish oil compared to those on placebo. The effect of copper was not significant. Since the number of patients in the trial is small, more trials are needed to support this claim.

High Cholesterol
A systematic review of studies that use fish oil to reduce cholesterol levels in people with type 2 diabetes mellitus. The researchers analyzed the results of 18 trials including 823 participants. Analysis of the data showed that fish oil was able to reduce triglycerides, however it increased low density lipoprotein (LDL or 'bad' cholesterol) levels. Fish oil supplementation did not affect glucose levels or the level of high density lipoprotein (HDL or 'good' cholesterol). Researchers also observed that while no adverse effects were reported, no trials attempted to determine if the fish oil supplementation would produce serious adverse effects.

Do Not Take If
  • You are taking Nonsteroidal Anti-inflammatory drugs (NSAIDS): (Fish oil can have additive anticoagulant/antiplatelet effects).
  • You are taking Glucocorticoids: Omega-3 supplements can worsen some side effects caused by glucocorticoids.
Side Effects
  • Fishy aftertaste
  • Loose stool
  • Nausea
Special Point

Omega-3 fatty acids should not be confused with omega-6 fatty acids, such as those found in evening primrose oil and borage oil, which have different effects in the body.

E-mail your questions and comments to