Nutritional Supplement

Fish Oil & Cod Liver Oil (EPA & DHA)

Also indexed as: Omega-3 Fatty Acids (Fish Oil), EPA (Fish Oil), Salmon Oil

Possible Deficiencies

So-called “primitive” diets have much higher levels of EPA and DHA than modern diets. As a result, some researchers and doctors believe that most people who eat a typical western diet are likely to be consuming less-than-optimal amounts of EPA and DHA. To a very limited extent, omega-3 fatty acids from vegetable sources, such as flaxseed oil, can be converted in the body to EPA.

At least four studies have reported a reduced blood level of omega-3 fatty acids in people with depression.191,192,193,194

People with rheumatoid arthritis have been found to have decreased levels of omega-3 fatty acids, such as are found in fish oil, in their joint fluid and blood.195

Side Effects

While those with heart disease and diabetes have often been reported to benefit from supplementation with fish oil,196,197 both groups should check with their doctor before taking more than 3 grams of fish oil per day for several months. Elevations in blood sugar and cholesterol levels may occur in some people who take fish oil.198

The increase in blood sugar appears to be related in part to the amount of fish oil used.199 The impairment of sugar metabolism sometimes caused by supplementation with fish oil has been prevented by the addition of half an hour of moderate exercise three times a week.200

While supplementation with fish oil consistently lowers triglycerides, the effect of fish oil on LDL (“bad”) cholesterol varies, and in some people, fish oil supplementation has been reported to increase LDL levels.201

There has been one case report in which a woman with a known allergy to crabs developed a severe allergic reaction after ingesting fish oil.202

References

1. Prichard BN, Smith CCT, Ling KLE, Betteridge DJ. Fish oils and cardiovascular disease. BMJ 1995;310:819-20 [editorial/review].

2. Von Schacky C, Fischer S, Weber PC. Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans. J Clin Invest 1985;76:1626-31.

3. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549-57 [review].

4. Adler AJ, Holub BJ. Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men. Am J Clin Nutr 1997;65:445-50.

5. Haglund O, Luostarinen R, Wallin R, et al. The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. J Nutr 1991;121:165-9.

6. Oostenbrug GS, Mensink RP, Hornstra G. A moderate in vivo vitamin E supplement counteracts the fish-oil-induced increase in in vitro oxidation of human low-density lipoproteins. Am J Clin Nutr 1993;57:827S.

7. Bercea CI, Cottrell GS, Tamagnini F, et al. Omega-3 polyunsaturated fatty acids and hypertension: a review of vasodilatory mechanisms of docosahexaenoic acid and eicosapentaenoic acid. Br J Pharmacol 2021;178:860–77.

8. Matsumoto C, Yoruk A, Wang L, et al. Fish and omega-3 fatty acid consumption and risk of hypertension. J Hypertens 2019 06;37(6):1223–9.

9. Yang B, Shi MQ, Li ZH, et al. Fish, Long-Chain n-3 PUFA and Incidence of Elevated Blood Pressure: A Meta-Analysis of Prospective Cohort Studies. Nutrients 2016 Jan;8(1):58.

10. Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials. Am J Hypertens 2014 Jul;27(7):885–96.

11. Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1223-30.

12. Nodari S, Triggiani M, Campia U, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol 2011;57:870-9.

13. Ando M, Sanaka T, Nihei H. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients. J Am Soc Nephrol 1999;10:2177-84.

14. Olszewski AJ, McCully KS. Fish oil decreases serum homocysteine in hyperlipemic men. Coron Artery Dis 1993;4:53-60.

15. Phillipson BE, Rothrock DW, Connor WE, et al. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med 1985;312:1210-6.

16. Haglund O, Wallin R, Luostarinen R, Saldeen T. Effects of a new fluid fish oil concentrate, ESKIMO-3, on triglycerides, cholesterol, fibrinogen and blood pressure. J Intern Med 1990;227:347-53.

17. Haglund O, Luostarinen R, Wallin W, Saldeen T. Effects of fish oil on triglycerides, lipoprotein(a), atherogenic index and fibrinogen. Influence of the degree of purification of the oil. Nutr Res 1992;12:455-68.

18. Haglund O, Luostarinen R, Wallin R, et al. The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. J Nutr 1991;121:165-9.

19. Leng GC, Lee AJ, Fowkes FG, et al. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Clin Nutr 1998;17:265-71.

20. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation 1994;90:2248-57.

21. Sacks FM, Stone PH, Gibson CM, et al. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995;25:1492-8.

22. von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.

23. Saynor R, Verel D, Gillott T. The long-term effect of dietary supplementation with fish lipid concentrate on serum lipids, bleeding time, platelets and angina. Atherosclerosis 1984;50:3-10.

24. Mehta JL, Lopez LM, Lawson D, et al. Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease. Effects on indices of platelet and neutrophil function and exercise performance. Am J Med 1988;84:45-52.

25. Wander RC, Du SH, Ketchum SO, Rowe KE. Alpha-tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil. J Nutr 1996;126:643-52.

26. Oostenbrug GS, Mensink RP, Hornstra G. A moderate in vivo vitamin E supplement counteracts the fish-oil-induced increase in in vitro oxidation of human low-density lipoproteins. Am J Clin Nutr 1993;57:827S.

27. von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.

28. Singh RB, Niaz MA, Sharma JP, et al. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival--4. Cardiovasc Drugs 1997;11:485-91.

29. [No authors listed]. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447-55.

30. Landmark K, Abdelnoor M, Urdal P, et al. Use of fish oils appears to reduce infarct size as estimated from peak creatine kinase and lactate dehydrogenase activities. Cardiology 1998;89:94-102.

31. Wander RC, Du SH, Ketchum SO, Rowe KE. Alpha-tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil. J Nutr 1996;126:643-52.

32. Carrero JJ, Lopez-Huertas E, Salmeron LM, et al. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease. J Nutr2005;135:1393-9.

33. Digiacomo RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud's phenomenon: a double-blind, controlled, prospective study. Am J Med 1989;86:158-64.

34. Sellmayer A, Witzgall H, Lorenz RL, Weber PC. Effects of dietary fish oil on ventricular premature complexes. Am J Cardiol 1995;76:974-7.

35. Hardarson T, Kristinsson A, Skuladottir G, et al. Cod liver oil does not reduce ventricular extrasystoles after myocardial infarction. J Intern Med 1989;236:33-7.

36. Raitt MH, Connor WE, Morris C, et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators. A randomized controlled trial. JAMA 2005;293:2884-91

37. Brouwer IA, Zock PL, Camm AJ, et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA2006;295:2613-9.

38. Shahar E, Folsom AR, Melnick SL, et al. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 1994;331:228-33.

39. Broekhuizen R, Wouters EFM, Creutzberg EC, et al. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 2005;60:376-82.

40. Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149-55.

41. Maes M, Smith R, Christophe A, et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35-46.

42. Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 1998;43:315-9.

43. Maes M, Christophe A, Delanghe J, et al. Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275-91.

44. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31:S157-S161.

45. Nemets H, Nemets B, Apter A, et al. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006;163:1098-100.

46. Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003;13:267-71.

47. Grenyer BFS, 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;31:1393-6.

48. 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;99:421-31.

49. Puri BK, Counsell SJ, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression. Arch Gen Psychiatry 2002;59:91-92 [Letter].

50. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002;59:913-9.

51. Buydens-Branchey L, Branchey M. n-3 polyunsaturated fatty acids decrease anxiety feelings in a population of substance abusers. J Clin Psychopharmacol 2006;26:661-5.

52. Deutch B. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr 1995;49:508-16.

53. Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996;174:1335-8.

54. Deutch B, Jørgensen EB, Hansen JC. Menstrual discomfort in Danish women reduced by dietary supplements of omega-3 PUFA and B12 (fish oil or seal oil capsules). Nutr Res 2000;20:621-31.

55. Zafari, M., Tofighi, M, Aghamohammady, A., Behmanesh, F., and Rakhshaee, Z. Comparison of the effect of fish oil and ibuprofen on treatment of severe pain in primary dysmenorrhea. Caspian J Intern Med. 2011 Summer;2(3):279-82.

56. Olsen SF, Secher NJ, Tabor A, et al. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. Brit J Obstet Gynecol 2000;107:382-95.

57. Steuerwald U, Weihe P, Jorgensen PJ, et al. Maternal seafood diet, methylmercury exposure, and neonatal neurologic function. J Pediatr 2000;136:599-605.

58. Birch EE, Castaneda YS, Wheaton DH, Birch DG, Uauy RD, Hoffman DR. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. Am J Clin Nutr 2005;81:871-9.

59. Yano Y. Effect of dietary supplementation with eicosapentaenoic acid on surgically induced endometriosis in the rabbit. Nippon Sanka Fujinka Gakkai Zasshi 1992 Mar;44(3):282-8 [in Japanese].

60. Covens AL, Christopher P, Casper RF. The effect of dietary supplementation with fish oil fatty acids on surgically induced endometriosis in the rabbit. Fertil Steril 1988;49:698-703.

61. Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996;174:1335-8.

62. Feher J, Kovacs B, Kovacs I, et al. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica2005;219:154-66.

63. Chua B, Flood V, Rochtchina E, Wang JJ, Smith W, Mitchell P. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol 2006;124:981-6.

64. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 2006;63:1402-8.

65. Kremer JM, Jubiz W, Michalek A, et al. Fish­oil fatty acid supplementation in active rheumatoid arthritis. Ann Int Med 1987;106(4):497-503.

66. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum 1990;33:810-20.

67. Geusens P, Wouters C, Nijs J, et al. Long­term effect of omega­3 fatty acid supplementation in active rheumatoid arthritis. Arthrit Rheum 1994;37:824-9.

68. Van der Tempel H, Tulleken JE, Limburg PC, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990;49:76-80.

69. Cleland LG, French JK, Betts WH, et al. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 1988;15(10):1471-5.

70. Kremer JM, Lawrence DA, Petrillow GF, et al. Effects of high­dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum 1995;38:1107-14.

71. Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, et al. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology 2008;47:665-9.

72. Proudman SM, James MJ, Spargo LD, et al. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis 2015;74:89–95.

73. Rajaei E, Mowla K, Ghorbani A, et al. The effect of omega-3 fatty acids in patients with active rheumatoid arthritis receiving DMARDs therapy: double-blind randomized controlled trial. Glob J Health Sci 2015;8:18–25.

74. Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985;312(19):1217-24.

75. Nordstrom DC, Honkanen VE, Nasu Y, et al. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 1995;14:231-4.

76. Altman R, Gray R. Inflammation in osteoarthritis. Clin Rheum Dis 1985;11:353.

77. Stammers T, Sibbald B, Freeling P. Fish oil in osteoarthritis. Lancet 1989;ii:503 [letter].

78. Stammers T, Sibbald B, Freeling P. Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Ann Rheum Dis 1992;51:128-9.

79. Bittiner SB, Tucker WFG, Cartwright I, Bleehen SS. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Lancet 1988;i:378-80.

80. Kojima T, Terano T, Tanabe E, et al. Long-term administration of highly purified eicosapentaenoic acid provides improvement of psoriasis. Dermatologica 1991;182:225-30.

81. Kojima T, Ternao T, Tanabe E, et al. Effect of highly purified eicosapentaenoic acid on psoriasis. J Am Acad Dermatol 1989;21:150-1.

82. Soyland E, Funk J, Rajka G, et al. Effect of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. N Engl J Med 1993;328:1812-6.

83. Dewsbury CE, Graham P, Darley CR. Topical eicosapentaenoic acid (EPA) in the treatment of psoriasis. Br J Dermatol 1989;120:581-4.

84. Mayser P, Mrowietz U, Arenberger P, et al. W-3 Fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial. J Am Acad Dermatol 1998;38:539-47.

85. Ashley JM, Lowe NJ, Borok ME, Alfin-Slater RB. Fish oil supplementation results in decreased hypertriglyceridemia in patients with psoriasis undergoing etretinate or acitretin therapy. J Am Acad Dermatol 1988;19:76-82.

86. Bjørneboe A, Søyland E, Bjørneboe GE, et al. Effect of dietary supplementation with eicosapentaenoic acid in the treatment of atopic dermatitis. Br J Dermatol 1987;117:463-9.

87. Bjørnboe A, Søyland E, Bjørnboe GE, et al. Effect of n-3 fatty acid supplement to patients with atopic dermatitis. J Intern Med Suppl 1989;225:233-6.

88. Søyland E, Rajka G, Bjørneboe A, et al. The effect of eicosapentaenoic acid in the treatment of atopic dermatitis. A clinical Study. Acta Derm Venereol (Stockh) 1989;144(Suppl):139.

89. Berth-Jones J, Graham-Brown RAC. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 1993;341:1557-60.

90. Søyland E, Funk J, Rajka G, et al. Dietary supplementation with very long-chain n-3 fatty acids in patients with atopic dermatitis. A double-blind multicentre study. Br J Dermatol 1994;130:757-64.

91. Rhodes LE, Durham BH, Fraser WD, Friedmann PS. Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption. J Invest Dermatol 1995;105:532-5.

92. McBeath EC, Zucker TF. The role of vitamin D in the control of dental caries in children. J Nutr 1938;15:547-64.

93. Buydens-Branchey L, Branchey M. n-3 polyunsaturated fatty acids decrease anxiety feelings in a population of substance abusers. J Clin Psychopharmacol 2006;26:661-5.

94. Horrobin DF. The relationship between schizophrenia and essential fatty acid and eicosanoid metabolism. Prostaglandins Leukot Essent Fatty Acids 1992;46:71-7 [review].

95. Horrobin DF. Schizophrenia as a membrane lipid disorder which is expressed throughout the body. Prostaglandins Leukot Essent Fatty Acids 1996;55:3-7 [review].

96. Warner R, Laugharne J, Peet M, et al. Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study. Biol Psychiatry 1999;45:1138-42.

97. Mahadik SP, Mukherjee S, Horrobin DF, et al. Plasma membrane phospholipid fatty acid composition of cultured skin fibroblasts from schizophrenic patients: comparison with bipolar patients and normal subjects. Psychiatry Res 1996;63:133-42.

98. Vaddadi KS, Gilleard CJ, Soosai E, et al. Schizophrenia, tardive dyskinesia and essential fatty acids. Schizophr Res 1996;20:287-94.

99. Peet M, Laugharne J, Rangarajan N, et al. Depleted red cell membrane essential fatty acids in drug-treated schizophrenic patients. J Psychiatr Res 1995;29:227-32.

100. Rudin DO. The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra. Biol Psychiatry 1981;16:837-50.

101. Puri BK, Richardson AJ, Horrobin DF, et al. Eicosapentaenoic acid treatment in schizophrenia associated with symptom remission, normalisation of blood fatty acids, reduced neuronal membrane phospholipid turnover and structural brain changes. Int J Clin Pract 2000;54:57-63.

102. Peet M, Laugharne JD, Mellor J, Ramchand CN. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins Leukot Essent Fatty Acids 1996;55:71-5.

103. Laugharne JD, Mellor JE, Peet M. Fatty acids and schizophrenia. Lipids 1996;31 Suppl:S163-5.

104. Pawełczyk T, Grancow-Grabka M, Kotlicka-Antczak M, et al. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res 2016;73:34–44.

105. Amminger GP, Schafer 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;67:146-54.

106. Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry 2001;158:2071-4.

107. Vaddadi KS, Courtney P, Gilleard CJ, et al. A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia. Psychiatry Res 1989;27:313-23.

108. Mellor JE, Laugharne JDE, Peet M. Omega-3 fatty acid supplementation in schizophrenic patients. Hum Psychopharmacol 1996;11:39-46.

109. Shah S, Ramchand CN, Peet M. Eicosapentaenoic acid (EPA) as an adjunct to neuroleptic therapy in the treatment of schizophrenia. Presented at the 9th Schizophrenia Winter Workshop, Davos, Switzerland, February 7-13, 1998.

110. Mellor JE, Peet M. Double-blind, placebo-controlled, trial of omega-3 fatty acids as an adjunct to the treatment of schizophrenia. Presented at the 9th Schizophrenia Winter Workshop, Davos, Switzerland, February 7-13, 1998.

111. Fenton WS, Hibbeln J, Knable M. Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biol Psychiatry 2000;47:8-21 [review].

112. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31:S157-S161.

113. Maes M, Christophe A, Delanghe J, et al. Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275-91.

114. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder. A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatr 1999;56:407-12.

115. Wozniak J, Biederman J, Mick E, et al. Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial. Eur Neuropsychopharmacol 2007;17:440-7.

116. Van Papendorp DH, Coetzer H, Kruger MC. Biochemical profile of osteoporotic patients on essential fatty acid supplementation. Nutr Res 1995;15:325–34.

117. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging 1998;10:385-94.

118. Van Papendorp DH, Coetzer H, Kruger MC. Biochemical profile of osteoporotic patients on essential fatty acid supplementation. Nutr Res 1995;15:325–34.

119. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging 1998;10:385-94.

120. Feher J, Kovacs B, Kovacs I, et al. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica2005;219:154-66.

121. McGuire R. Fish oil cuts lower ocular pressure. Med Tribune 1991;Sept 19:25.

122. Chua B, Flood V, Rochtchina E, Wang JJ, Smith W, Mitchell P. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol 2006;124:981-6.

123. Deutch B. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr 1995;49:508-16.

124. Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996;174:1335-8.

125. Deutch B, Jørgensen EB, Hansen JC. Menstrual discomfort in Danish women reduced by dietary supplements of omega-3 PUFA and B12 (fish oil or seal oil capsules). Nutr Res 2000;20:621-31.

126. Zafari, M., Tofighi, M, Aghamohammady, A., Behmanesh, F., and Rakhshaee, Z. Comparison of the effect of fish oil and ibuprofen on treatment of severe pain in primary dysmenorrhea. Caspian J Intern Med. 2011 Summer;2(3):279-82.

127. Yano Y. Effect of dietary supplementation with eicosapentaenoic acid on surgically induced endometriosis in the rabbit. Nippon Sanka Fujinka Gakkai Zasshi 1992 Mar;44(3):282-8 [in Japanese].

128. Covens AL, Christopher P, Casper RF. The effect of dietary supplementation with fish oil fatty acids on surgically induced endometriosis in the rabbit. Fertil Steril 1988;49:698-703.

129. Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996;174:1335-8.

130. Kalupahana NS, Claycombe KJ, Moustaid-Moussa N. (n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights. Adv Nutr 2011 Jul;2(4):304–16.

131. Albracht-Schulte K, Kalupahana NS, Ramalingam L, et al. Omega-3 fatty acids in obesity and metabolic syndrome: a mechanistic update. J Nutr Biochem 2018 08;58:1–16.

132. Keshavarz SA, Mostafavi SA, Akhondzadeh S, et al. Omega-3 supplementation effects on body weight and depression among dieter women with co-morbidity of depression and obesity compared with the placebo: A randomized clinical trial. Clin Nutr ESPEN 2018 06;25:37–43.

133. Zhang YY, Liu W, Zhao TY, et al. Efficacy of Omega-3 Polyunsaturated Fatty Acids Supplementation in Managing Overweight and Obesity: A Meta-Analysis of Randomized Clinical Trials. J Nutr Health Aging 2017;21(2):187–92.

134. Arm JP, Horton CE, Eiser NM, et al. The effects of dietary supplementation with fish oil on asthmatic responses to antigen. J Allergy Clin Immunol 1988;81:183 [abstract #57].

135. Mickleborough TD, Lindley MR, Ionescu AA, Fly AD. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest2006;129:39-49.

136. Broughton KS, Johnson CS, Pace BK, et al. Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production. Am J Clin Nutr 1997;65:1011-7.

137. Dry J, Vincent D. Effect of a fish oil diet on asthma: results of a 1-year double-blind study. Int Arch Allergy Appl Immunol 1991;95:156-7.

138. Thien FC, Woods RK, Waters EH. Oily fish and asthma—a fishy story? Med J Aust 1996;164:135-6 [editorial].

139. Fogarty A, Britton J. The role of diet in the aetiology of asthma. Clin Exp Allergy 2000;30:615-27.

140. Hodge L, Salome CM, Peat JK, et al. Consumption of oily fish and childhood asthma risk. Med J Austral 1996;164:137-40.

141. Nagakura T, Matsuda S, Shichijyo K, et al. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Respir J 2000;16:861-5.

142. Salomon P, Kornbluth AA, Janowitz HD. Treatment of ulcerative colitis with fish oil n--3-omega-fatty acid: an open trial. J Clin Gastroenterol 1990;12:157-61.

143. Stenson WF, Cort D, Rodgers J, et al. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 1992;116:609-14.

144. Hawthorne AB, Daneshmend TK, Hawkey CJ, et al. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut 1992;33:922-8.

145. Aslan A, Triadafilopoulos G. Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Am J Gastroenterol 1992;87:432-7.

146. Dichi I, Frenhane P, Dichi JB, et al. Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Nutrition 2000;16:87-90.

147. Edman JS, Williams WH, Atkins RC. Nutritional therapies for ulcerative colitis: literature review, chart review study, and future research. Altern Ther Health Med 2000;6:55-63.

148. Mate J, Castanos R, Garcia-Samaniego J, Pajares JM. Does dietary fish oil maintain the remission of Crohn's disease: a case control study. Gastroenterology 1991;100:A228 [abstract].

149. Belluzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 1996;334:1557-60.

150. Olsen SF, Secher NJ, Tabor A, et al. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. Brit J Obstet Gynecol 2000;107:382-95.

151. Steuerwald U, Weihe P, Jorgensen PJ, et al. Maternal seafood diet, methylmercury exposure, and neonatal neurologic function. J Pediatr 2000;136:599-605.

152. Birch EE, Castaneda YS, Wheaton DH, Birch DG, Uauy RD, Hoffman DR. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. Am J Clin Nutr 2005;81:871-9.

153. Sibai BM. Prevention of preeclampsia: A big disappointment. Am J Obstet Gynecol 1998;179:1275-8 [review].

154. Williams MA, Zingheim RW, King IB, Zebelman AM. Omega-3 fatty acids in maternal erythrocytes and risk for preeclampsia. Epidemiology 1995;6:232-7.

155. Laivuori H, Hovatta O, Viinikka L, Ylikorkala O. Dietary supplementation with primrose oil or fish oil does not change urinary excretion of prostacyclin and thromboxane metabolites in pre-eclamptic women. Prostaglandins Leukot Essent Fatty Acids 1993;49:691-4.

156. Onwude JL, Lilford RJ, Hjartardottier H, et. al. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol 1995;109:95-100.

157. Salvig JD, Olsen SF, Secher NJ. Effects of fish oil supplementation in late pregnancy on blood pressure: a randomised controlled trial. Br J Obstet Gynaecol 1996;103:529-33.

158. Kelley VE, Ferretti A, Izui S, Strom TB. A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-1pr mice. J Immunol 1985;134:2914-9.

159. Walton AJE, Snaith ML, Locniskar M, et al. Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus. Ann Rheum Dis 1991;50:463-6.

160. Westberg G, Tarkowski A. Effect of MaxEPA in patients with SLE. Scand J Rheumatology 1990;19:137-43.

161. Wright SA, O'Prey FM, McHenry MT, et al. A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus. Ann Rheum Dis 2008;67:841-8.

162. Gerster H. The use of n-3 PUFAs (fish oil) in enteral nutrition. Int J Vitam Nutr Res 1995;65:3-20 [review].

163. Kollman KA, Lien EL, Vanderhoof JA. Dietary lipids influence intestinal adaptation after massive bowel resection. J Pediatr Gastroenterol Nutr 1999;28:41-5.

164. Johnson JA 3d, Griswold JA, Muakkassa FF. Essential fatty acids influence survival in sepsis. J Trauma 1993;35:128-31.

165. Wachtler P, Konig W, Senkal M, et al. Influence of a total parenteral nutrition enriched with omega-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. J Trauma 1997;42:191-8.

166. Gianotti L, Braga M, Fortis C, et al. A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. JPEN J Parenter Enteral Nutr 1999;23:314-20.

167. Tashiro T, Yamamori H, Takagi K, et al. n-3 versus n-6 polyunsaturated fatty acids in critical illness. Nutrition 1998;14:551-3.

168. Gerster H. The use of n-3 PUFAs (fish oil) in enteral nutrition. Int J Vitam Nutr Res 1995;65:3-20 [review].

169. Meydani SN, Lichtenstein AH, Cornwall S, et al. Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived n-3 fatty acid enrichment. J Clin Invest 1993;92:105-13.

170. Kelley DS, Taylor PC, Nelson GJ, et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 1999;34:317-24.

171. Wu D, Meydani SN. n-3 polyunsaturated fatty acids and immune function. Proc Nutr Soc 1998;57:503-9 [review].

172. Niinisto S, Takkinen H, Erlund I, et al. Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity. Diabetologia 2017;60:1223–33.

173. Norris J, Kroehl M, Fingerlin T, et al. Erythrocyte membrane docosapentaenoic acid levels are associated with islet autoimmunity: The Diabetes Autoimmunity Study in the Young. Diabetologia 2014;57:295–304.

174. Miller M, Yin X, Seifert J, et al. Erythrocyte membrane omega-3 fatty acid levels and omega-3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: the Diabetes Autoimmunity Study in the Young (DAISY). Pediatr Diabetes 2011;12:669–75.

175. Lamichhane A, Crandell J, Jaacks L, et al. Longitudinal associations of nutritional factors with glycated hemoglobin in youth with type 1 diabetes: the SEARCH Nutrition Ancillary Study. Am J Clin Nutr 2015;101:1278–85.

176. Mayer-Davis E, Dabelea D, Crandell J, et al. Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study. Diabetes Care 2013;36:1842–50.

177. Stiefel P, Ruiz-Gutierrez V, Gajon E, et al. Sodium transport kinetics, cell membrane lipid composition, neural conduction and metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention. Ann Nutr Metab 1999;43:113–20.

178. Lee C, Sharp S, Wexler D, Adler A. Dietary intake of eicosapentaenoic and docosahexaenoic acid and diabetic nephropathy: cohort analysis of the diabetes control and complications trial. Diabetes Care 2010;33:1454–6.

179. Lewis E, Perkins B, Lovblom L, et al. Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial. Neurology 2017;88:2294–301.

180. Gutstein A, Copple T. Cardiovascular disease and omega-3s: Prescription products and fish oil dietary supplements are not the same. J Am Assoc Nurse Pract 2017;29:791–801.

181. Telle-Hansen V, Gaundal L, Myhrstad M. Polyunsaturated Fatty Acids and Glycemic Control in Type 2 Diabetes. Nutrients 2019;11.

182. Abbott K, Burrows T, Thota R, et al. Do omega-3 PUFAs affect insulin resistance in a sex-specific manner? A systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2016;104:1470–84.

183. O'Mahoney L, Matu J, Price O, et al. Omega-3 polyunsaturated fatty acids favorably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials. Cardiovasc Diabetol 2018;17:98.

184. Gao H, Geng T, Huang T, Zhao Q. Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis. Lipids Health Dis 2017;16:131.

185. McCarren T, Hitzemann R, Allen C, et al. Amelioration of severe migraine by fish oil (omega-3) fatty acids. Am J Clin Nutr 1985;41:874 [abstract].

186. Glueck CJ, McCarren T, Hitzemann R, et al. Amelioration of severe migraine with omega-3 fatty acids: a double-blind placebo controlled clinical trial. Am J Clin Nutr 1986;43:710 [abstract].

187. Puri BK. The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids 2004;70:399-401.

188. Gaby, AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing, 2011.

189. Belluzzi A, Brignola C, Campieri M, et al. Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients. Dig Dis Sci 1994;39:2589-94.

190. Burns CP, Halabi S, Clamon GH, et al. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res 1999;5:3942-7.

191. Maes M, Smith R, Christophe A, et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35-46.

192. Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149-55.

193. Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 1998;43:315-9.

194. Maes M, Christophe A, Delanghe J, et al. Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275-91.

195. Navarro E, Esteve M, Olivé A, et al. Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids. J Rheumatol 2000;27:298-303.

196. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549-57 [review].

197. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 1991;14:1160-79.

198. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988;37:1567-73.

199. Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. Ann Intern Med 1995;123:911-8.

200. Dunstan DW, Burke V, Mori TA, et al. The independent and combined effects of aerobic exercise and dietary fish intake on serum lipids and glycemic control in NIDDM. Diabetes Care 1997;20:913-21.

201. Harris WS, Zucker ML, Dujovne CA. Omega-3 fatty acids in type IV hyperlipidemia: fish oils vs. methyl esters. Am J Clin Nutr 1987;45:858 [abstract].

202. Kmet A, Unger J, Jahangir K, Kolber MR. Fish-oil capsule ingestion: a case of recurrent anaphylaxis. Can Fam Physician 2012;58:e379-81.

Copyright © 2025 TraceGains, Inc. All rights reserved.

Learn more about TraceGains, the company.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2025.