Micronutrients and Supplements Info: Omega-3 and Omega-6 Fatty Acids
Omega-3 and Omega-6 Fatty Acids
Description

Fatty acids are long-chain hydrocarbon molecules with a polar acid end and a non-polar hydrocarbon end. Humans and mammals can usually synthesize most important fatty acids except for two groups of fatty acids that have an important role to play in various systems. Those are: linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid). Because the body cannot synthesize them, they are called essential fatty acids and must be obtained from the diet.

A small percentage of the alpha-linolenic acid provided through the diet is further transformed into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the body.  Those, also members of the omega-3 group, have very important roles to play in the body. The transformation of alpha-linolenic acid into EPA and DHA by the body does unfortunately not appear to be a very efficient process and for this reason and under certain conditions, EPA and DHA can at times also be considered as essential, meaning that they need to be obtained from dietary sources.


Function

Omega-3 and Omega-6 fatty acids are important components of the cell membrane. DHA is also particularly important for retinal cell membranes, as well is for neuronal cell membrane.

Recent studies have demonstrated the important role played by Omega-3 and Omega-6 fatty acids in the functioning of various systems as well as in the prevention of several diseases.  To give some examples, Omega-3 and -6 fatty acids have been investigated for their:

  • important roles in visual and neurological development of the infant
  • important roles in vision
  • important role in central nervous system activities
  • association with a reduced risk of coronary heart disease and stroke
  • association with decrease levels of triglycerides
  • role in inflammation responses
  • role in the maintenance of healthy immune functions
  • potential role in risk reduction of Alzheimer’s diseases and other types of dementia


Sources

Oily fish is the best dietary source of Omega-3 (and EPA and DHA) fatty acids. Other good sources of Omega-3 are algae and flaxseed oil. It is also commonly used as a supplement.


Toxicity

Fish oil supplements are generally safe. However, fish oils may interact with some medications, other vitamins (e.g., vitamin A and E) or other supplements. If you have a disease or medical condition, if you take any medication, or if you are pregnant or nursing, it is advisable to consult a health care provider before taking omega-3 supplements. It is also advisable to consult a health care provider if you intend to treat a child with omega-3 supplements.


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Scientific References



Books


Lipids: absorption and transport. Lichtenstein AH, Jones PJ. In: Bowman BA, Russel RM, eds. Present Knowledge in Nutrition. 8th ed. Washington, D. C.: ILSI Press; 2001:93-103

PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001.


Scientific Articles

  Fish oil, omega-3 and omega-6 fatty acids and:



Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Kris-Etherton PM, Harris WS, Appel LJ. Circulation. 2002;106(21):2747-2757. 
[Abstract]

Eurodiet: Nutrition and Diet for Healthy Lifestyles in Europe. European Commission Directorate General for Health and Consumer Protection. 2001.

Fish intake, contaminants, and human health: evaluating the risks and the benefits. Mozaffarian D, Rimm EB. JAMA. 2006;296(15):1885-1899. 
[Abstract]

Fish or pills? Consumer Reports. 2003;68(7):30-32.

Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Melanson SF, Lewandrowski EL, Flood JG, Lewandrowski KB. Arch Pathol Lab Med. 2005;129(1):74-77.
[Abstract]

Reduction of organochlorine contaminants from fish oil during refining. Hilbert G, Lillemark L, Balchen S, Hojskov CS. Chemosphere. 1998;37(7):1241-1252.
[Abstract]

Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy. Bender NK, Kraynak MA, Chiquette E, Linn WD, Clark GM, Bussey HI. J Thromb Thrombolysis. 1998;5(3):257-261. 
[Abstract]

Fish oil interaction with warfarin. Buckley MS, Goff AD, Knapp WE. Ann Pharmacother. 2004;38(1):50-52. 
[Abstract]

Relationship between vitamin E requirement and polyunsaturated fatty acid intake in man: a review. Valk EE, Hornstra G. Int J Vitam Nutr Res. 2000;70(2):31-42. 
[Abstract]

Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Higdon JV, Liu J, Du SH, Morrow JD, Ames BN, Wander RC. Am J Clin Nutr. 2000;72(3):714-722. 
[Abstract]

alpha-Tocopherol influences in vivo indices of lipid peroxidation in postmenopausal women given fish oil. Wander RC, Du SH, Ketchum SO, Rowe KE. J Nutr. 1996;126(3):643-652. 
[Abstract]

Oxidation of plasma proteins is not increased after supplementation with eicosapentaenoic and docosahexaenoic acids. Wander RC, Du SH. Am J Clin Nutr. 2000;72(3):731-737. 
[Abstract]

Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. Harris WS, Mozaffarian D, Lefevre M, et al. J Nutr. 2009;139(4):804S-819S. 
[Abstract]

Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Nakamura MT, Nara TY. Annu Rev Nutr. 2004;24:345-376.  [Abstract]

Alpha-linolenic acid metabolism in men and women: nutritional and biological implications. Burdge G. Curr Opin Clin Nutr Metab Care. 2004;7(2):137-144. 
[Abstract]

Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men.  Burdge GC, Jones AE, Wootton SA. Br J Nutr. 2002;88(4):355-364.
[Abstract]

Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Burdge GC, Wootton SA. Br J Nutr. 2002;88(4):411-420.
[Abstract]

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects. Giltay EJ, Gooren LJ, Toorians AW, Katan MB, Zock PL. Am J Clin Nutr. 2004;80(5):1167-1174. 
[Abstract]

Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials.Muskiet FA, Fokkema MR, Schaafsma A, Boersma ER, Crawford MA. J Nutr. 2004;134(1):183-186. 
[Abstract]

Problems with essential fatty acids: time for a new paradigm? Cunnane SC. Prog Lipid Res. 2003;42(6):544-568. 
[Abstract]

Docosahexaenoic acid: membrane properties of a unique fatty acid. Stillwell W, Wassall SR. Chem Phys Lipids. 2003;126(1):1-27. 
[Abstract]

The role of docosahexaenoic acid in retinal function. Jeffrey BG, Weisingerb HS, Neuringer M, Mitcheli DC. Lipids. 2001;36(9):859-871.
[Abstract]

The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. SanGiovanni JP, Chew EY. Prog Retin Eye Res. 2005;24(1):87-138. 
[Abstract]

Omega-3 polyunsaturated fatty acid regulation of gene expression. Price PT, Nelson CM, Clarke SD. Curr Opin Lipidol. 2000;11(1):3-7. 
[Abstract]

Polyunsaturated fatty acid regulation of gene expression. Sampath H, Ntambi JM. Nutr Rev. 2004;62(9):333-339. 
[Abstract]

Fatty acid regulation of gene transcription. Jump DB. Crit Rev Clin Lab Sci. 2004;41(1):41-78. 
[Abstract]

Docosahexaenoic acid (DHA) and hepatic gene transcription. Jump DB, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Chem Phys Lipids. 2008;153(1):3-13.
[Abstract]

N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Jump DB. Curr Opin Lipidol. 2008;19(3):242-247. 
[Abstract]

Fatty acid regulation of hepatic gene transcription. Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O. J Nutr. 2005;135(11):2503-2506. 
[Abstract]

Essential fatty acids in visual and brain development. Uauy R, Hoffman DR, Peirano P, Birch DG, Birch EE. Lipids. 2001;36(9):885-895. 
[Abstract]

First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula. Carlson SE, Cooke RJ, Werkman SH, Tolley EA. Lipids. 1992;27(11):901-907.
[Abstract]

An n-3 fatty acid deficiency impairs rat spatial learning in the Barnes maze. Fedorova I, Hussein N, Baumann MH, Di Martino C, Salem N, Jr. Behav Neurosci. 2009;123(1):196-205. 
[Abstract]

Omega-3 fatty acids and rodent behavior. Fedorova I, Salem N, Jr. Prostaglandins Leukot Essent Fatty Acids. 2006;75(4-5):271-289. 
[Abstract]

Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system. Larque E, Demmelmair H, Koletzko B. Ann N Y Acad Sci. 2002;967:299-310. 
[Abstract]

Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. Innis SM. J Pediatr. 2003;143(4 Suppl):S1-8. 
[Abstract]

Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission. Chalon S, Vancassel S, Zimmer L, Guilloteau D, Durand G. Lipids. 2001;36(9):937-944. 
[Abstract]

Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. J Pediatr. 2003;143(4 Suppl):S17-25. 
[Abstract]

Longchain polyunsaturated fatty acid supplementation in preterm infants. Simmer K, Patole S. Cochrane Database Syst Rev. 2004(1):CD000375. 
[Abstract]

Longchain polyunsaturated fatty acid supplementation in infants born at term. Simmer K. Cochrane Database Syst Rev. 2001(4):CD000376.
[Abstract]

Effects of n-3 long chain polyunsaturated fatty acid supplementation on visual and cognitive development throughout childhood: a review of human studies. Eilander A, Hundscheid DC, Osendarp SJ, Transler C, Zock PL. Prostaglandins Leukot Essent Fatty Acids. 2007;76(4):189-203. 
[Abstract]

Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. SanGiovanni JP, Parra-Cabrera S, Colditz GA, Berkey CS, Dwyer JT. Pediatrics. 2000;105(6):1292-1298. 
[Abstract]

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. O'Connor DL, Hall R, Adamkin D, et al. Pediatrics. 2001;108(2):359-371. 
[Abstract]

Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Fewtrell MS, Morley R, Abbott RA, et al. Pediatrics. 2002;110(1 Pt 1):73-82. 
[Abstract]

Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. Fewtrell MS, Abbott RA, Kennedy K, et al. J Pediatr. 2004;144(4):471-479. 
[Abstract]

Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. Clandinin MT, Van Aerde JE, Merkel KL, et al. J Pediatr. 2005;146(4):461-468. 
[Abstract]

Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. Birch EE, Castaneda YS, Wheaton DH, Birch DG, Uauy RD, Hoffman DR. Am J Clin Nutr. 2005;81(4):871-879. 
[Abstract]

Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Auestad N, Scott DT, Janowsky JS, et al. Pediatrics. 2003;112(3 Pt 1):e177-183. 
[Abstract]

Randomized trials with polyunsaturated fatty acid interventions in preterm and term infants: functional and clinical outcomes. Gibson RA, Chen W, Makrides M. Lipids. 2001;36(9):873-883. 
[Abstract]

Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula. Birch EE, Garfield S, Castaneda Y, Hughbanks-Wheaton D, Uauy R, Hoffman D. Early Hum Dev. 2007;83(5):279-284. 
[Abstract]

Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. McCann JC, Ames BN. Am J Clin Nutr. 2005;82(2):281-295. 
[Abstract]

Efficacy and safety of docosahexaenoic acid and arachidonic acid addition to infant formulas: can one buy better vision and intelligence? Koo WW. J Am Coll Nutr. 2003;22(2):101-107. 
[Abstract]

Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation. Makrides M, Gibson RA. Am J Clin Nutr. 2000;71(1 Suppl):307S-311S.
[Abstract]

A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Onwude JL, Lilford RJ, Hjartardottir H, Staines A, Tuffnell D. Br J Obstet Gynaecol. 1995;102(2):95-100. 
[Abstract]

Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Olsen SF, Sorensen JD, Secher NJ, et al. Lancet. 1992;339(8800):1003-1007. 
[Abstract]

A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Smuts CM, Huang M, Mundy D, Plasse T, Major S, Carlson SE. Obstet Gynecol. 2003;101(3):469-479. 
[Abstract]

Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials. Szajewska H, Horvath A, Koletzko B. Am J Clin Nutr. 2006;83(6):1337-1344. 
[Abstract]

Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. BJOG. 2000;107(3):382-395. 
[Abstract]

Effect of supplementation of women in high-risk pregnancies with long-chain polyunsaturated fatty acids on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials. Horvath A, Koletzko B, Szajewska H. Br J Nutr. 2007;98(2):253-259. 
[Abstract]

The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. Koletzko B, Lien E, Agostoni C, et al. J Perinat Med. 2008;36(1):5-14. 
[Abstract]

Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Pediatrics. 2003;111(1):e39-44.
[Abstract]

Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Dunstan JA, Simmer K, Dixon G, Prescott SL. Arch Dis Child Fetal Neonatal Ed. 2008;93(1):F45-50. 
[Abstract]

Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Judge MP, Harel O, Lammi-Keefe CJ. Am J Clin Nutr. 2007;85(6):1572-1577. 
[Abstract]

Polyunsaturated fatty acids and cardiovascular health. Kris-Etherton PM, Hecker KD, Binkoski AE. Nutr Rev. 2004;62(11):414-426.
[Abstract]

Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Burr ML, Fehily AM, Gilbert JF, et al. Lancet. 1989;2(8666):757-761. 
[Abstract]

Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Circulation. 1999;99(6):779-785. 
[Abstract]

Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial). Tuttle KR, Shuler LA, Packard DP, et al. Am J Cardiol. 2008;101(11):1523-1530. 
[Abstract]

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(9177):447-455. 
[Abstract]

Hypertriglyceridemia as a cardiovascular risk factor. Austin MA, Hokanson JE, Edwards KL. Am J Cardiol. 1998;81(4A):7B-12B. 
[Abstract]

n-3 fatty acids and serum lipoproteins: human studies. Harris WS. Am J Clin Nutr. 1997;65(5 Suppl):1645S-1654S. 
[Abstract]

Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Atherosclerosis. 2006;189(1):19-30. 
[Abstract]

Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults. Harris WS, Kris-Etherton PM, Harris KA. Curr Atheroscler Rep. 2008;10(6):503-509. 
[Abstract]

Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Marchioli R, Barzi F, Bomba E, et al. Miocardico (GISSI)-Prevenzione. Circulation. 2002;105(16):1897-1903. 
[Abstract]

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. Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M. Cardiovasc Drugs Ther. 1997;11(3):485-491. 
[Abstract]

Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Nilsen DW, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L. Am J Clin Nutr. 2001;74(1):50-56.
[Abstract]

N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Bucher HC, Hengstler P, Schindler C, Meier G. Am J Med. 2002;112(4):298-304. 
[Abstract]

Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. Sacks FM, Stone PH, Gibson CM, Silverman DI, Rosner B, Pasternak RC. J Am Coll Cardiol. 1995;25(7):1492-1498. 
[Abstract]

The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. Ann Intern Med. 1999;130(7):554-562.  [Abstract]

Effects of omega-3 fatty acids on cardiovascular risk factors and intermediate markers of cardiovascular disease. Balk E, Chung M, Lichtenstein A, et al. Evid Rep Technol Assess (Summ). 2004(93):1-6. 
[Abstract]

Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Lichtenstein AH, Appel LJ, Brands M, et al. Circulation. 2006;114(1):82-96. 
[Abstract]

Diet, serum cholesterol, and death from coronary heart disease. The Western Electric study. Shekelle RB, Shryock AM, Paul O, et al. N Engl J Med. 1981;304(2):65-70. 
[Abstract]

Dietary fat intake and risk of coronary heart disease in women: 20 years of follow-up of the nurses' health study. Oh K, Hu FB, Manson JE, Stampfer MJ, Willett WC. Am J Epidemiol. 2005;161(7):672-679. 
[Abstract]

Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. BMJ. 1996;313(7049):84-90. 
[Abstract]

Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Laaksonen DE, Nyyssonen K, Niskanen L, Rissanen TH, Salonen JT. Arch Intern Med. 2005;165(2):193-199. 
[Abstract]

Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease. Sacks FM, Katan M. Am J Med. 2002;113 Suppl 9B:13S-24S. 
[Abstract]

Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Mensink RP, Katan MB. Arterioscler Thromb. 1992;12(8):911-919.
[Abstract]

Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Frantz ID, Jr., Dawson EA, Ashman PL, et al. Arteriosclerosis. 1989;9(1):129-135. 
[Abstract]

Dietary prevention of coronary heart disease in women: the Finnish mental hospital study. Miettinen M, Turpeinen O, Karvonen MJ, Pekkarinen M, Paavilainen E, Elosuo R. Int J Epidemiol. 1983;12(1):17-25.
[Abstract]

Omega-6 Fatty Acids and Risk for Cardiovascular Disease: A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Harris WS, Mozaffarian D, Rimm E, et al. Circulation. 2009;119:Epub ahead of print.
[Abstract][Full Text][Full Text PDF]

Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Mozaffarian D, Ascherio A, Hu FB, et al. Circulation. 2005;111(2):157-164. 
[Abstract]

Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Hu FB, Stampfer MJ, Manson JE, et al. Am J Clin Nutr. 1999;69(5):890-897. 
[Abstract]

Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Dolecek TA. Proc Soc Exp Biol Med. 1992;200(2):177-182. 
[Abstract]

Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Pietinen P, Ascherio A, Korhonen P, et al. Am J Epidemiol. 1997;145(10):876-887.
[Abstract]

alpha-Linolenic acid intake is not beneficially associated with 10-y risk of coronary artery disease incidence: the Zutphen Elderly Study. Oomen CM, Ocke MC, Feskens EJ, Kok FJ, Kromhout D. Am J Clin Nutr. 2001;74(4):457-463. 
[Abstract]

Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary heart disease. Albert CM, Oh K, Whang W, et al. Circulation. 2005;112(21):3232-3238. 
[Abstract]

Does alpha-linolenic acid intake reduce the risk of coronary heart disease? A review of the evidence. Mozaffarian D. Altern Ther Health Med. 2005;11(3):24-30. 
[Abstract]

Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review. Wendland E, Farmer A, Glasziou P, Neil A. Heart. 2006;92(2):166-169.  [Abstract]

Increased alpha-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Bemelmans WJ, Lefrandt JD, Feskens EJ, et al. Eur J Clin Nutr. 2004;58(7):1083-1089. 
[Abstract]

Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Rallidis LS, Paschos G, Liakos GK, Velissaridou AH, Anastasiadis G, Zampelas A. Atherosclerosis. 2003;167(2):237-242. 
[Abstract]

Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM. J Nutr. 2004;134(11):2991-2997. 
[Abstract]

Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Kris-Etherton PM, Harris WS, Appel LJ. Arterioscler Thromb Vasc Biol. 2003;23(2):151-152. 
[Abstract]

n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Wang C, Harris WS, Chung M, et al. Am J Clin Nutr. 2006;84(1):5-17. 
[Abstract]

Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. Hooper L, Thompson RL, Harrison RA, et al. BMJ. 2006;332(7544):752-760.
[Abstract]

The inverse relation between fish consumption and 20-year mortality from coronary heart disease. Kromhout D, Bosschieter EB, de Lezenne Coulander C. N Engl J Med. 1985;312(19):1205-1209. 
[Abstract]

Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE. Circulation. 2003;107(14):1852-1857. 
[Abstract]

The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Kromhout D, Feskens EJ, Bowles CH. Int J Epidemiol. 1995;24(2):340-345.
[Abstract]

Dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial (MRFIT). Dolecek TA, Granditis G. World Rev Nutr Diet. 1991;66:205-216. 
[Abstract]

Fish consumption and the 30-year risk of fatal myocardial infarction. Daviglus ML, Stamler J, Orencia AJ, et al. N Engl J Med. 1997;336(15):1046-1053. 
[Abstract]

Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China. Yuan JM, Ross RK, Gao YT, Yu MC. Am J Epidemiol. 2001;154(9):809-816. 
[Abstract]

Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. Hu FB, Bronner L, Willett WC, et al. JAMA. 2002;287(14):1815-1821.  [Abstract]

Intake of fish and long-chain n-3 fatty acids and the risk of coronary heart mortality in men and women. Jarvinen R, Knekt P, Rissanen H, Reunanen A. Br J Nutr. 2006;95(4):824-829. 
[Abstract]

Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Iso H, Kobayashi M, Ishihara J, et al. Circulation. 2006;113(2):195-202. 
[Abstract]

Association between fish consumption and all-cause and cause-specific mortality in Japan: NIPPON DATA80, 1980-99. Nakamura Y, Ueshima H, Okamura T, et al. Am J Med. 2005;118(3):239-245. 
[Abstract]

Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. Leaf A, Xiao YF, Kang JX, Billman GE. Pharmacol Ther. 2003;98(3):355-377
[Abstract]

Fish consumption and risk of sudden cardiac death. Albert CM, Hennekens CH, O'Donnell CJ, et al. JAMA. 1998;279(1):23-28. 
[Abstract]

Blood levels of long-chain n-3 fatty acids and the risk of sudden death. Albert CM, Campos H, Stampfer MJ, et al. N Engl J Med. 2002;346(15):1113-1118. 
[Abstract]

Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Mozaffarian D. Am J Clin Nutr. 2008;87(6):1991S-1996S.
[Abstract]

Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Leaf A, Albert CM, Josephson M, et al. Circulation. 2005;112(18):2762-2768. 
[Abstract]

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. Raitt MH, Connor WE, Morris C, et al. JAMA. 2005;293(23):2884-2891. 
[Abstract]

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. Brouwer IA, Zock PL, Camm AJ, et al. JAMA. 2006;295(22):2613-2619. 
[Abstract]

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis. Jenkins DJ, Josse AR, Beyene J, et al. Cmaj. 2008;178(2):157-164. 
[Abstract]

Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and Office Of Dietary Supplements Omega-3 Fatty Acids and their Role in Cardiac Arrhythmogenesis Workshop. London B, Albert C, Anderson ME, et al. Circulation. 2007;116(10):e320-335. 
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Fish consumption and risk of stroke. The Zutphen Study. Keli SO, Feskens EJ, Kromhout D. Stroke. 1994;25(2):328-332. 
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The relationship between fish consumption and stroke incidence. The NHANES I Epidemiologic Follow-up Study (National Health and Nutrition Examination Survey). Gillum RF, Mussolino ME, Madans JH. Arch Intern Med. 1996;156(5):537-542. 
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Fish consumption and cardiovascular disease in the physicians' health study: a prospective study. Morris MC, Manson JE, Rosner B, Buring JE, Willett WC, Hennekens CH. Am J Epidemiol. 1995;142(2):166-175. 
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Fish consumption and stroke in men. 30-year findings of the Chicago Western Electric Study. Orencia AJ, Daviglus ML, Dyer AR, Shekelle RB, Stamler J. Stroke. 1996;27(2):204-209. 
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Habitual fish consumption and risk of incident stroke: the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Myint PK, Welch AA, Bingham SA, et al. Public Health Nutr. 2006;9(7):882-888. 
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Intake of fish and omega-3 fatty acids and risk of stroke in women. Iso H, Rexrode KM, Stampfer MJ, et al. JAMA. 2001;285(3):304-312. 
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Fish consumption and risk of stroke in men. He K, Rimm EB, Merchant A, et al. JAMA. 2002;288(24):3130-3136.
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Fish consumption and incidence of stroke: a meta-analysis of cohort studies. He K, Song Y, Daviglus ML, et al. Stroke. 2004;35(7):1538-1542. 
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The molecular bases of Alzheimer's disease and other neurodegenerative disorders. Maccioni RB, Munoz JP, Barbeito L. Arch Med Res. 2001;32(5):367-381. 
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Fatty acids, lipid metabolism and Alzheimer pathology. Hooijmans CR, Kiliaan AJ. Eur J Pharmacol. 2008;585(1):176-196. 
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DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease. National Institutes of Health. ClinicalTrials.
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Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Lipids. 2000;35(12):1305-1312. 
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Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Tully AM, Roche HM, Doyle R, et al. Br J Nutr. 2003;89(4):483-489. 
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Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Schaefer EJ, Bongard V, Beiser AS, et al. Arch Neurol. 2006;63(11):1545-1550. 
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Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Montori VM, Farmer A, Wollan PC, Dinneen SF. Diabetes Care. 2000;23(9):1407-1415. 
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Elevated plasma glucose and lowered triglyceride levels from omega-3 fatty acid supplementation in type II diabetes. Friday KE, Childs MT, Tsunehara CH, Fujimoto WY, Bierman EL, Ensinck JW. Diabetes Care. 1989;12(4):276-281. 
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Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. MacLean CH, Mojica WA, Morton SC, et al. Evid Rep Technol Assess (Summ). 2004(89):1-4. 
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Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Franz MJ, Bantle JP, Beebe CA, et al. Diabetes Care. 2003;26 Suppl 1:S51-61. 
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Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Nordstrom DC, Honkanen VE, Nasu Y, Antila E, Friman C, Konttinen YT. Rheumatol Int. 1995;14(6):231-234. 
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Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Harbige LS. Lipids. 2003;38(4):323-341. 
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Polyunsaturated fatty acids and inflammation. Calder PC. Prostaglandins Leukot Essent Fatty Acids. 2006;75(3):197-202. 
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Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. Fortin PR, Lew RA, Liang MH, et al. J Clin Epidemiol. 1995;48(11):1379-1390.  [Abstract]

A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Goldberg RJ, Katz J. Pain. 2007;129(1-2):210-223. 
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Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease--a randomized, placebo-controlled, double-blind cross-over trial. Lorenz R, Weber PC, Szimnau P, Heldwein W, Strasser T, Loeschke K. J Intern Med Suppl. 1989;225(731):225-232. 
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Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group). Lorenz-Meyer H, Bauer P, Nicolay C, et al. Scand J Gastroenterol. 1996;31(8):778-785.
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Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. N Engl J Med. 1996;334(24):1557-1560. 
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Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study. Romano C, Cucchiara S, Barabino A, Annese V, Sferlazzas C. World J Gastroenterol. 2005;11(45):7118-7121. 
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Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Aslan A, Triadafilopoulos G. Am J Gastroenterol. 1992;87(4):432-437. 
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Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Hawthorne AB, Daneshmend TK, Hawkey CJ, et al. Gut. 1992;33(7):922-928. 
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Dietary supplementation with fish oil in ulcerative colitis. Stenson WF, Cort D, Rodgers J, et al. Ann Intern Med. 1992;116(8):609-614. 
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n-3 fatty acids only delay early relapse of ulcerative colitis in remission. Loeschke K, Ueberschaer B, Pietsch A, et al. Dig Dis Sci. 1996;41(10):2087-2094. 
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Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Hodge L, Salome CM, Hughes JM, et al. Eur Respir J. 1998;11(2):361-365. 
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Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma. Okamoto M, Mitsunobu F, Ashida K, et al. Intern Med. 2000;39(2):107-111. 
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Clinical efficacy of n-3 fatty acid supplementation in patients with asthma. Wong KW. J Am Diet Assoc. 2005;105(1):98-105. 
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Health effects of omega-3 fatty acids on asthma. Schachter HM, Reisman J, Tran K, et al. Evid Rep Technol Assess (Summ). 2004(91):1-7. 
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Dietary marine fatty acids (fish oil) for asthma in adults and children. Woods RK, Thien FC, Abramson MJ. Cochrane Database Syst Rev. 2002(3):CD001283. 
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Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review. Reisman J, Schachter HM, Dales RE, et al. BMC Complement Altern Med. 2006;6:26. 
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A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. Donadio JV, Jr., Bergstralh EJ, Offord KP, Spencer DC, Holley KE. N Engl J Med. 1994;331(18):1194-1199. 
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The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Donadio JV, Jr., Grande JP, Bergstralh EJ, Dart RA, Larson TS, Spencer DC. Mayo Nephrology Collaborative Group. J Am Soc Nephrol. 1999;10(8):1772-1777. 
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A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. Donadio JV, Jr., Larson TS, Bergstralh EJ, Grande JP. J Am Soc Nephrol. 2001;12(4):791-799. 
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Treatment of severe IgA nephropathy with omega-3 fatty acids: the effect of a "very low dose" regimen. Alexopoulos E, Stangou M, Pantzaki A, Kirmizis D, Memmos D. Ren Fail. 2004;26(4):453-459. 
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The effect of fish-oil dietary supplement on the progression of mesangial IgA glomerulonephritis. Cheng IK, Chan PC, Chan MK. Nephrol Dial Transplant. 1990;5(4):241-246. 
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Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Pettersson EE, Rekola S, Berglund L, et al. Clin Nephrol. 1994;41(4):183-190. 
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Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. Hogg RJ, Lee J, Nardelli N, et al. Clin J Am Soc Nephrol. 2006;1(3):467-474. 
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Short-term effects of fish oil treatment on urinary excretion of high- and low-molecular weight proteins in patients with IgA nephropathy. Branten AJ, Klasen IS, Wetzels JF. Clin Nephrol. 2002;58(4):267-274. 
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Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. Dillon JJ. J Am Soc Nephrol. 1997;8(11):1739-1744. 
[Abstract]

An "evidence-based" survey of therapeutic options for IgA nephropathy: assessment and criticism. Strippoli GF, Manno C, Schena FP. Am J Kidney Dis. 2003;41(6):1129-1139. 
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Fish consumption and major depression. Hibbeln JR. Lancet. 1998;351(9110):1213. 
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Cross-national comparisons of seafood consumption and rates of bipolar disorders. Noaghiul S, Hibbeln JR. Am J Psychiatry. 2003;160(12):2222-2227.  [Abstract]

Lowered omega-3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY. Psychiatry Res. 1999;85(3):275-291.  [Abstract]

Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Peet M, Murphy B, Shay J, Horrobin D. Biol Psychiatry. 1998;43(5):315-319. 
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Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Am J Clin Nutr. 2003;78(1):40-46. 
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Depression and adipose essential polyunsaturated fatty acids. Mamalakis G, Tornaritis M, Kafatos A. Prostaglandins Leukot Essent Fatty Acids. 2002;67(5):311-318. 
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Omega-3 fatty acids in major depression. Locke CA, Stoll AL. World Rev Nutr Diet. 2001;89:173-185. 
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Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA. Prostaglandins Leukot Essent Fatty Acids. 2005;72(3):211-218. 
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Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Grenyer BF, Crowe T, Meyer B, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(7):1393-1396. 
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No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Rogers PJ, Appleton KM, Kessler D, et al. Br J Nutr. 2008;99(2):421-431. 
[Abstract]

A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ. Am J Psychiatry. 2003;160(5):996-998. 
[Abstract]

Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Su KP, Huang SY, Chiu CC, Shen WW. Eur Neuropsychopharmacol. 2003;13(4):267-271. 
[Abstract]

omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Zanarini MC, Frankenburg FR. Am J Psychiatry. 2003;160(1):167-169. 
[Abstract]

Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Am J Psychiatry. 2006;163(6):1098-1100. 
[Abstract]

Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Stoll AL, Severus WE, Freeman MP, et al. Arch Gen Psychiatry. 1999;56(5):407-412. 
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Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Keck PE, Jr., Mintz J, McElroy SL, et al. Biol Psychiatry. 2006;60(9):1020-1022. 
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Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. Osher Y, Bersudsky Y, Belmaker RH. J Clin Psychiatry. 2005;66(6):726-729. 
[Abstract]

Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Frangou S, Lewis M, McCrone P. Br J Psychiatry. 2006;188:46-50. 
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A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. Lin PY, Su KP. J Clin Psychiatry. 2007;68(7):1056-1061. 
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Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. Freeman MP, Hibbeln JR, Wisner KL, et al. J Clin Psychiatry. 2006;67(12):1954-1967. 
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Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Appleton KM, Hayward RC, Gunnell D, et al. Am J Clin Nutr. 2006;84(6):1308-1316. 
[Abstract]

Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group. Assies J, Lieverse R, Vreken P, Wanders RJ, Dingemans PM, Linszen DH. Biol Psychiatry. 2001;49(6):510-522. 
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Low essential fatty acid and B-vitamin status in a subgroup of patients with schizophrenia and its response to dietary supplementation. Kemperman RF, Veurink M, van der Wal T, et al. Prostaglandins Leukot Essent Fatty Acids. 2006;74(2):75-85. 
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Fatty acid levels in the brains of schizophrenics and normal controls. Horrobin DF, Manku MS, Hillman H, Iain A, Glen M. Biol Psychiatry. 1991;30(8):795-805. 
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Fatty acids and schizophrenia. Laugharne JD, Mellor JE, Peet M. Lipids. 1996;31 Suppl:S163-165. 
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Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Peet M, Brind J, Ramchand CN, Shah S, Vankar GK. Schizophr Res. 2001;49(3):243-251. 
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Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ. Am J Psychiatry. 2002;159(9):1596-1598. 
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The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Emsley R, Niehaus DJ, Koen L, et al. Schizophr Res. 2006;84(1):112-120. 
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A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M. Am J Psychiatry. 2001;158(12):2071-2074. 
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A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. Peet M, Horrobin DF. J Psychiatr Res. 2002;36(1):7-18. 
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Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. Joy CB, Mumby-Croft R, Joy LA. Cochrane Database Syst Rev. 2003(2):CD001257.
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The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Vaddadi KS. Prostaglandins Med. 1981;6(4):375-379. 
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Essential fatty acid deficiency in patients receiving home parenteral nutrition. Jeppesen PB, Hoy CE, Mortensen PB. Am J Clin Nutr. 1998;68(1):126-133. 
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The possible role of essential fatty acids in the pathophysiology of malnutrition: a review. Smit EN, Muskiet FA, Boersma ER. Prostaglandins Leukot Essent Fatty Acids. 2004;71(4):241-250. 
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Essential fatty acid deficiency and home total parenteral nutrition patients. Mascioli EA, Lopes SM, Champagne C, Driscoll DF. Nutrition. 1996;12(4):245-249. 
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Absence of the biochemical symptoms of essential fatty acid deficiency in surgical patients undergoing protein sparing therapy. Stegink LD, Freeman JB, Wispe J, Connor WE. Am J Clin Nutr. 1977;30(3):388-393. 
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Deficiencies of essential fatty acids, vitamin A and E and changes in plasma lipoproteins in patients with reduced fat absorption or intestinal failure. Jeppesen PB, Hoy CE, Mortensen PB. Eur J Clin Nutr. 2000;54(8):632-642.
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Direct transesterification of plasma fatty acids for the diagnosis of essential fatty acid deficiency in cystic fibrosis. Lepage G, Levy E, Ronco N, Smith L, Galeano N, Roy CC. J Lipid Res. 1989;30(10):1483-1490. 
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A case of human linolenic acid deficiency involving neurological abnormalities. Holman RT, Johnson SB, Hatch TF. Am J Clin Nutr. 1982;35(3):617-623
[Abstract]