: Omega-3: EFAs:

We need at least 5 g of essential fatty acids each day.
Grains, fruits and vegetables provide omega-6 and/or omega-3 fatty acids, but oil made from cold-water fish areis the best source of omega-3 fats.

Dosage:

Typical dosage of EPA & DHA is 3 to 9 grams a day. Up to 60 grams a day has been used in research.

The main omega-3 fatty acids in fish oil are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Most major studies use at least 1,800 mg EPA and 900 mg DHA for each day.

DHA may be more effective than EPA for thinning the blood¹⁷⁶ and reducing blood pressure,¹⁰⁵ while EPA may better reduce triglyceride levels.^160�165

Vitamin E may be added or oxygen removed for stability. Fish oil may be assayed for organochlorines and PCBs.

Flaxseed oil contains omega-3 precursors, but is not as therapeutic as preformed DHA and EPA.¹

Therapeuty-Use:

According to most studies, fish and fish oils help prevent death from heart disease.¹⁵² They help prevent atherosclerosis, reducing high triglyceride levels, raising the HDL cholesterol level, thinning the blood, reducing homocysteine, and sometimes reducing blood pressure.^{14,15,51,90-94,96�105,151,160�165,174,177} These effects also help prevent strokes.^20,178

Fish oil is helpful in the early stages of rheumatoid arthritis. It reduces symptoms without causing side effects and can be synergistic with other arthritis remedies including conventional drugs.^37,38,179

Two studies show that fish oil may be effective for the pain of dysmenorrhea.^39,40

One small double-blind�study finds benefits in�bipolar disorder (manic-depression) with high doses of fish oil improving emotional state and reducing risk of relapse.⁴¹ Benefits may also be found for those with depression,^154,168schizophrenia,^{48,148,169,170} and borderline personality disorder.¹⁸⁰

Small studies suggest benefits in Raynaud's phenomenon (abnormal sensitivity in the extremeties to cold temperatures),^42,43�sickle-cell anemia,⁴⁵ and a form of kidney disease called IgA nephropathy,⁴⁷ and the autoimmune disease lupus.¹³⁷ (However, two studies failed to find fish oil helpful for kidney disease caused by lupus.^138,139)

Evidence is mixed regarding whether fish oil is beneficial for Crohn's disease or ulcerative colitis, conditions in which parts of the digestive tract are highly inflamed.^{49�51,61�68, 159}

According to some, but not all studies, fish oil may help treat the undesired weight loss often experienced by people with cancer.^181,182 In addition, highly preliminary evidence hints that DHA might enhance the effects of the cancer chemotherapy drug doxorubicin,¹⁵⁷ and decrease side effects of the chemotherapy drug irinotecan.¹⁵⁸

Use of fish oil by pregnant women might help support healthy brain function in their children¹⁸³ and help prevent premature birth.^184,185

Interesting, but highly preliminary, evidence suggests that fish oil, or its constituents, might be helpful for treating kidney stones, alleviating the symptoms of chronic fatigue syndrome, and reducing the risk of prostate cancer.^54,56�59

Fish oil has also been proposed as a treatment for many other conditions, including diabetic neuropathy,⁶⁰allergies, and gout, but there has been little real scientific investigation of these uses.

Some, but not all, studies suggest that fish oil combined with omega-6 essential fatty acids may augment the effectiveness of calcium in the treatment of osteoporosis.^86,87 One promising, but highly preliminary, double-blind, placebo-controlled study suggests that the same combination therapy may improve symptoms of the severe neurological illness called Huntington�s disease.¹⁵⁵

For several other conditions, the current balance of the evidence suggests that fish oil is not effective.

For example, despite widely publicized claims that fish oil helps asthma, most preliminary studies have failed to provide evidence that it is effective, and one study found that fish oil can actually worsen aspirin-related asthma.^69�77,171

Similarly, a�16-week, double-blind, placebo-controlled�study of 167 individuals with recurrent migraine headaches found that fish oil did not significantly reduce headache frequency or severity.¹⁴⁹ Conflicting results have been seen in other, much smaller trials of fish oil for migraines.^172,173

Fish oil is also sometimes recommended for enhancing immunity in HIV infection. However, one 6-month double-blind study found that a combination of the omega-3 fatty acids in fish oil plus the amino acid arginine was no more effective than placebo in improving immune function in people with HIV.⁷⁸ Fish oil, however, might help individuals with HIV gain weight.⁷⁹

Preliminary studies suggested that fish oil could help symptoms of multiple sclerosis; however, one double-blind study found no difference between people taking fish oil and those taking olive oil (used as a placebo).^80�84

Although one study found fish oil somewhat helpful in psoriasis,¹³³ a much larger study found no benefit.¹³⁴

DHA has been evaluated as a possible treatment for male infertility, but a double-blind trial of 28 men with impaired sperm activity found no benefit.⁸⁵

In another study, DHA failed to augment the effectiveness of standard therapy for attention deficit disorder.⁸⁹ However, a study that evaluated the potential benefits of fish oil combined with omega-6 fatty acids found some evidence of benefit.⁸⁸

Combination therapy with GLA and fish oil has failed to prove effective for cyclic breast pain.¹⁸⁶

Heart Disease Prevention

Studies on fish or fish oil for preventing cardiovascular disease, slowing the progression of cardiovascular disease, and preventing heart-related death have returned somewhat contradictory results.^{106�125,150,156} However, a review (technically a meta-analysis) of many studies on the subject suggests that when all the evidence is put together, it appears that fish or fish oil can reduce overall mortality, heart disease mortality, and sudden cardiac death (e.g., fatal arrythmia).¹⁵²

As noted earlier, fish oil is thought to exert several separate effects that act together to help protect the heart. The most important action of fish oil may be its apparent ability to reduce high triglyceride levels. Like cholesterol, triglycerides are a type of fat in the blood that tends to damage the arteries, leading to heart disease. According to most, though not all, studies, fish oil supplements can reduce triglycerides by about 25�30%.^90�93,151

Fish oil has been specifically studied for reducing triglyceride levels in people with diabetes, and it appears to do so safely and effectively.³ It also seems to remain effective in individuals who are already using statin drugs to control lipid levels.^14,15 However, one study found that the standard drug gemfibrozil is more effective than fish oil for reducing triglycerides.⁹⁴

Some, but not all studies suggest that fish, fish oil, or EPA or DHA separately may additionally raise the level of HDL ("good") cholesterol.^{96,97,151,164,165} This too should help prevent heart disease.

Additionally, fish oil may help the heart by "thinning" the blood and by reducing blood levels of homocysteine.^98,176

Studies contradict one another on whether fish oil can lower blood pressure,^99�104,177 but on balance the supplement does seem to exert a modest positive effect.¹⁷⁴ A 6-week, double-blind, placebo-controlled study of 59 overweight men suggests that the DHA in fish oil, but not the EPA, is responsible for this benefit.¹⁰⁵

Rheumatoid Arthritis

The results of numerous small double-blind trials indicate that omega-3 fatty acids in fish oil can help reduce the symptoms of rheumatoid arthritis.^{126,127,179,187} The benefits of fish oil effect may be enhanced by a vegetarian diet.¹⁸⁷ However, unlike some conventional treatments, fish oil probably does not slow the progression of rheumatoid arthritis.

Menstrual Pain

Regular use of fish oil may reduce the pain of menstrual cramps.

In a 4-month study of 42 young women aged 15 to 18, half the participants received a daily dose of 6 g of fish oil, providing 1,080 mg of EPA and 720 mg of DHA daily.¹²⁸ After 2 months, they were switched to placebo for another 2 months. The other group received the same treatments in reverse order. The results showed that these young women experienced significantly less menstrual pain while they were taking fish oil.

Another double-blind study followed 78 women, who received either fish oil, seal oil, fish oil with vitamin B₁₂ (7.5 mcg daily), or placebo for three full menstrual periods.¹²⁹ Significant improvements were seen in all treatment groups, but the fish oil plus B₁₂ proved most effective, and its benefits continued for the longest time after treatment was stopped (3 months). The researchers offered no explanation why B₁₂ should be helpful.

Bipolar Disorder

A 4-month, double-blind, placebo-controlled study of 30 individuals suggests that fish oil can enhance the effects of standard treatments for bipolar disorder,�reducing risk of�relapse and improving emotional state.¹³⁰ Eleven of the 14 individuals who took fish oil improved or remained well during the course of the study, while only 6 out of the 16 given placebo responded similarly.

The study will now be repeated by Baylor University and Harvard Medical School/McLean Hospital, enrolling 120 people for a period of 3 years.

Depression

A 4-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in 20 individuals with depression.¹⁵⁴ All but one participant were also taking standard antidepressants and had been taking them for at least 3 months. By week 3, the level of depression had improved to a significantly greater extent in the fish oil group than in placebo group. Six of 10 participants given fish oil, but only one of 10 given placebo, showed at least a 50% reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a �cure.�)

A double-blind, placebo-controlled study of 70 people who were still depressed despite standard therapy found that additional treatment with ethyl-EPA (a modified form of EPA) improved symptoms.¹⁷⁵ However, one double-blind study failed to find DHA alone helpful for depression.¹

⁸⁸

Raynaud's Phenomenon

In small, double-blind studies, fish oil has been found to reduce the severe finger and toe responses to cold temperatures that occur in Raynaud's phenomenon.^131,132 However, these studies suggest that a higher than usual dosage must be used to get results, perhaps 12 g daily.

Osteoporosis

There is some evidence that essential fatty acids may enhance the effectiveness of calcium in osteoporosis. In one study, 65 postmenopausal women were given calcium along with either placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil) for a period of 18 months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group.¹³⁵

However, a 12-month, double-blind trial of 42 postmenopausal women found no benefit.¹³⁶

The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and already received enough essential fatty acids in their diet.

Lupus

Lupus is a serious autoimmune disease that can cause numerous problems, including fatigue, joint pain, and kidney disease. One small, 34-week, double-blind, placebo-controlled crossover study compared placebo against daily doses of EPA (20 g) from fish oil.¹³⁷ A total of 17 individuals completed the trial. Of these, 14 showed improvement when taking EPA, while only 4 did so when treated with placebo.

Other small studies failed to find fish oil helpful for lupus nephritis (kidney damage caused by lupus).^138,139

Attention Deficit and Hyperactivity Disorder (ADHD)

Essential fatty acids are essential for brain development and function. EFAs are helpful for ADHD and learning. A double-blind, placebo-controlled trial of fish oil and evening primrose oil improves ADHD symptoms.¹⁴⁰ DHA is not effective, on the other hand, when children are

taking stimulant drugs in a double-blind, placebo-controlled trial.¹⁴¹

Safety

Fish oils should be assayed for purity as they can contain toxins such as heavy metals, organochlorines and PCBs.¹⁶⁶

Fish oil is a gentle blood-thinner, so check with your physician before combining it with blood-thinning drugs Coumadin (warfarin, rat poison) or heparin. Contrary to some reports, fish oil does not appear to cause bleeding,¹⁴² even with aspirin.¹⁴³

Fish oil doesn't raise blood sugar levels in diabetics.^144,145

Fish oil can temporarily raise the LDL cholesterol level.^146,147

If you use cod liver oil, read the label and stay within the safe maximum intake of vitamin A and vitamin D. These vitamins are fat soluble, so they can potentially build up to toxic levels. The official maximum daily intake of vitamin A is 3,000 mcg for adults including pregnant women.

Interactions

EPA and DHA could reduce the need for Coumadin (warfarin) and Heparin. Talk to your physician before combining.

References:

1. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645�S1654.

2. Shekelle RB, Shryock AM, Paul O, et al. Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. N Engl J Med. 1981;304:65�70.

3. Kromhout D, Bosschieter EB, De Lezenne Coulander C. The inverse relation between fish consumption and 20- year mortality from coronary heart disease. N Engl J Med. 1985;312:1205�1209.

4. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645�S1654.

5. Cobiac L, Clifton PM, Abbey M, et al. Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n�3 fatty acids in mildly hyperlipidemic males. Am J Clin Nutr. 1991;53:1210�1216.

6. Dyerberg J. N-3 fatty acids and coronary artery disease: potentials and problems. Omega-3, Lipoproteins, and Atherosclerosis. 1996;27:251�258.

7. Lungershausen YK, Abbey M, Nestel PJ, et al. Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives. J Hypertens. 1994;12:1041�1045.

8. Radack K, Deck C, Huster G. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial. Arch Intern Med. 1991;151:1173�1180.

9. Singer P, Jaeger W, Wirth M, et al. Lipid and blood pressure-lowering effect of mackerel diet in man. Atherosclerosis. 1983;49:99�108.

10. Singer P, Melzer S, Goschel M, et al. Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension. 1990;16:682�691.

11. Whelton PK, Kumanyika SK, Cook NR, et al. Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: Results from phase 1 of the Trials of Hypertension Prevention. Am J Clin Nutr. 1997;65(suppl 2):S652�S660.

12. 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�562.

13. Mori TA, Bao DQ, Burke V, et al. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999;34:253�260.

14. Montori VM, Farmer A, Wollan PC, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000;23:1407�1415.

15. Durrington PN, Bhatnagar D, Mackness MI, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544�548.

16. Harris WS. N-3 fatty acids and lipoproteins: comparison of results from human and animal studies. Lipids. 1996;31:243�252.

17. Nenseter MS, Osterud B, Larsen T, et al. Effect of Norwegian fish powder on risk factors for coronary heart disease among hypercholesterolemic individuals. Nutr Metab Cardiovasc Dis. 2000;10:323�330.

18. van Dam M, Stalenhoef AF, Wittekoek J, et al. Efficacy of concentrated n-3 fatty acids in hypertriglyceridaemia: a comparison with gemfibrozil. Clin Drug Invest. 2001;21:175�181.

19. Guallar E, Hennekens CH, Sacks FM, et al. A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians. J Am Coll Cardiol. 1995;25:387�394.

20. Iso H, Rexrode KM, Stampfer MJ, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. 2001;285:304�312.

21. Shekelle RB, Missell LV, Paul O, et al. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:820�821.

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

23. Kromhout D, Feskens EJ, Bowles CH. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol. 1995;24:340�345.

24. Vollset SE, Heuch I, Bjelke E. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:820�821.

25. Curb JD, Reed DM. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:821�822.

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

27. Ascherio A, Rimm EB, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995;332:977�982.

28. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 1994;90:2248�2257.

29. 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�1498.

30. [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�455.

31. de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994;343:1454�1459.

32. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363�1367.

33. Billman GE, Hallaq H, Leaf A. Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids. Proc Natl Acad Sci U S A. 1994;91:4427�4430.

34. Sellmayer A, Witzgall H, Lorenz RL, et al. Effects of dietary fish oil on ventricular premature complexes. Am J Cardiol. 1995;76:974�977.

35. Nilsen DW, Albrektsen G, Landmark K, et al. 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. Am J Clin Nutr. 2001;74:50�56.

36. Angerer P, Stork S, Kothny W, et al. Effect of marine omega-3 fatty acids on peripheral atherosclerosis in patients with coronary artery disease�a randomised 2 year intervention trial [abstract]. Eur Heart J. 2001;22(suppl):162.

37. James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum. 1997;27:85�97.

38. Volker D, Fitzgerald P, Major G, et al. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol. 2000;27:2343�2346.

39. Harel Z, Biro FM, Kottenhahn RK, et al. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol. 1996;174:1335�1338.

40. Deutch B, Jorgensen 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�631.

41. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56:407�412.

42. 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�164.

43. Ringer TV, Hughes GS, Spillers CR, et al. Fish oil blunts the pain response to cold pressor testing in normal males [abstract]. J Am Coll Nutr. 1989;8:435.

44. Bittiner SB, Cartwright I, Tucker WFG, et al. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Lancet. 1988;1:378�380.

45. Tomer A, Kasey S, Connor WE, et al. Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. Thromb Haemost. 2001;85:966�974.

46. 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�466.

47. Donadio JV Jr, Grande JP, Bergstralh EJ, et al. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. J Am Soc Nephrol. 1999;10:1772�1777.

48. Peet M, Brind J, Ramchand CN, et al. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res. 2001;49:243�251.

49. 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�1560.

50. Lorenz-Meyer H, Bauer P, Nicolay C, et al. 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). Scand J Gastroenterol.1996;31:778�785.

51. Lorenz R, Weber PC, Szimnau P, et al. Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease�a randomized, placebo-controlled, double-blind cross-over trial. J Intern Med Suppl. 1989;225:225�232.

52. Iso H, Rexrode KM, Stampfer MJ, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. 2001;285:301�312.

54. Hibbeln JR, Salem N Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr. 1995;62:1�9.

56. Buck AC, Jenkins A, Lingam K, et al. The treatment of idiopathic recurrent urolithiasis with fish oil (EPA) and evening primrose oil (GLA)�a double blind study. J Urol. 1993;149:253A.

57. Norrish AE, Skeaff CM, Arribas GLB, et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. Br J Cancer. 1999;81:1238�1242.

58. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990;82:209�216.

59. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand. 1999;99:112�116.

60. Gerbi A, Maixent JM, Ansaldi JL, et al. Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats. J Nutr. 1999;129:207�213.

61. Halsted CH, Ghandi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med. 1981;305:1513�1517.

62. 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�437.

63. Almallah YZ, El-Tahir A, Heys SD, et al. Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition. Eur J Clin Invest. 2000;30:58�65.

64. Stenson WF, Cort D, Rodgers J, et al. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med. 1992;116:609�614.

65. 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�928.

66. Greenfield SM, Green AT, Teare JP, et al. A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis. Aliment Pharmacol Ther. 1993;7:159�166.

67. 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�928.

68. Loeschke K, Ueberschaer B, Pietsch A, et al.n-3 fatty acids only delay early relapse of ulcerative colitis in remission. Dig Dis Sci. 1996;41:2087�2094.

69. Thien FC, Woods RK, Walters EH. Oily fish and asthma�a fishy story? Med J Aust. 1996;164:135�136.

70. Arm JP, Thien FC, Lee TH. Leukotrienes, fish-oil, and asthma. Allergy Proc. 1994;15:129�134.

71. Picado C, Castillo JA, Schinca N, et al. Effects of a fish oil enriched diet on aspirin intolerant asthmatic patients: a pilot study. Thorax. 1988;43:93�97.

72. Woods RK, Thien FC, Abramson MJ. Dietary marine fatty acids (fish oil) for asthma. Cochrane Database Syst Rev. 2000;4:1�12 +5 tables.

73. Dry J, Vincent D. Effect of a fish oil diet on asthma: Results of a one-year double-blind study. Int Arch Allergy Immunol. 1991;95:156�157.

74. Stenius-Aarniala B, Aro A, Hakulinen A, et al. Evening primrose oil and fish oil are ineffective as supplementary treatment of bronchial asthma. Ann Allergy.1989;62:534�547.

75. Arm J. The effects of dietary supplementation with fish oil on asthmatic responses to antigen. J Allergy Clin Immunol. 1988;81:183.

76. Stenius-Aarniala B, Aro A, Hakulinen A, et al. Symptomatic effects of evening primrose oil, fish oil, and olive oil in patients with bronchial asthma. Ann Allergy. 1985;55:330.

77. Lee TH, Arm JP. Prospects for modifying the allergic response by fish oil diets. Clin Allergy. 1986;16:89�100.

78. Pichard C, Sudre P, Karsegard V, et al. A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study. AIDS. 1998;12:53�63.

79. Scevola D, Oberto L, Faggi A, et al. Fish oil in the treatment of wasting syndrome. Int Conf AIDS. 1996;11:122.

80. Nightingale S, Woo E, Smith AD, et al. Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis. Acta Neurol Scand. 1990;82:43�50.

81. Cunnane SC, Ho SY, Dore-Duffy P, et al. Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis. Am J Clin Nutr. 1989;50:801�806.

82. Gallai V, Sarchielli P, Trequattrini A, et al. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol. 1995;56:143�153.

83. Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses. 1986;21:193�200.

84. Bates D. Dietary lipids and multiple sclerosis. Ups J Med Sci Suppl. 1990;48:173�187.

85. Conquer JA, Martin JB, Tummon I, et al. Effect of DHA supplementation on DHA status and sperm motility in asthenozoospermic males. Lipids. 2000;35:149�154.

86. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998;10:385�394.

87. Bassey EJ, Littlewood JJ, Rothwell MC, et al. Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of EfacalW v. calcium alone. Br J Nutr. 2000;83:629�635.

88. Richardson AJ, Puri BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:233�239.

89. Voigt RG, Llorente AM, Jensen CL, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. 2001;139:189�196.

90. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645�S1654.

91. Durrington PN, Bhatnagar D, Mackness MI, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544�548.

92. Harris WS. N-3 fatty acids and lipoproteins: comparison of results from human and animal studies. Lipids. 1996;31:243�252.

93. Nenseter MS, Osterud B, Larsen T, et al. Effect of Norwegian fish powder on risk factors for coronary heart disease among hypercholesterolemic individuals. Nutr Metab Cardiovasc Dis. 2000;10:323�330.

94. van Dam M, Stalenhoef AF, Wittekoek J, et al. Efficacy of concentrated n-3 fatty acids in hypertriglyceridaemia: a comparison with gemfibrozil. Clin Drug Invest. 2001;21:175�181.

95. Montori VM, Farmer A, Wollan PC, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000;23:1407�1415.

96. Cobiac L, Clifton PM, Abbey M, et al. Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n�3 fatty acids in mildly hyperlipidemic males. Am J Clin Nutr. 1991;53:1210�1216.

97. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645�S1654.

98. Dyerberg J. N-3 fatty acids and coronary artery disease: potentials and problems. Omega-3, Lipoproteins, and Atherosclerosis. 1996;27:251�258.

99. Lungershausen YK, Abbey M, Nestel PJ, et al. Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives. J Hypertens. 1994;12:1041�1045.

100. Radack K, Deck C, Huster G. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial. Arch Intern Med. 1991;151:1173�1180.

101. Singer P, Jaeger W, Wirth M, et al. Lipid and blood�pressure-lowering effect of mackerel diet in man. Atherosclerosis. 1983;49:99�108.

102. Singer P, Melzer S, Goschel M, et al. Fish oil amplifies the effect of propranolol in mild essential hypertension. Hypertension. 1990;16:682�691.

103. Appel LJ, Miller ER III, Seidler AJ, et al. Does supplementation of diet with 'fish oil' reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med. 1993;153:1429�1438.

104. Whelton PK, Kumanyika SK, Cook NR, et al. Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: Results from phase 1 of the Trials of Hypertension Prevention. Am J Clin Nutr. 1997;65(suppl 2):S652�S660.

105. Mori TA, Bao DQ, Burke V, et al. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999;34:253�260.

106. Guallar E, Hennekens CH, Sacks FM, et al. A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians. J Am Coll Cardiol. 1995;25:387�394.

107. Iso H, Rexrode KM, Stampfer MJ, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. 2001;285:304�312.

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

109. Shekelle RB, Missell LV, Paul O, et al. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:820�821.

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

111. Kromhout D, Feskens EJ, Bowles CH. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol. 1995;24:340�345.

112. Vollset SE, Heuch I, Bjelke E. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:820�821.

113. Curb JD, Reed DM. Fish consumption and mortality from coronary heart disease [letter]. N Engl J Med. 1985;313:821�822.

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

115. Ascherio A, Rimm EB, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995;332:977�982.

116. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 1994;90:2248�2257.

117. 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�1498.

118. [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�455.

119. Angerer P, Stork S, Kothny W, et al. Effect of marine omega-3 fatty acids on peripheral atherosclerosis in patients with coronary artery disease�a randomised 2 year intervention trial [abstract]. Eur Heart J. 2001;22(suppl):162.

120. de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994;343:1454�1459.

121. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363�1367.

122. Billman GE, Hallaq H, Leaf A. Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids. Proc Natl Acad Sci U S A. 1994;91:4427�4430.

123. Sellmayer A, Witzgall H, Lorenz RL, et al. Effects of dietary fish oil on ventricular premature complexes. Am J Cardiol. 1995;76:974�977.

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

125. Nilsen DW, Albrektsen G, Landmark K, et al. 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. Am J Clin Nutr. 2001;74:50�56.

126. James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum. 1997;27:85�97.

127. Volker D, Fitzgerald P, Major G, et al. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol. 2000;27:2343�2346.

128. Harel Z, Biro FM, Kottenhahn RK, et al. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol. 1996;174:1335�1338.

129. Deutch B, Jorgensen 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�631.

130. Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry. 1999;56:407�412.

131. 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�164.

132. Ringer TV, Hughes GS, Spillers CR, et al. Fish oil blunts the pain response to cold pressor testing in normal males [abstract]. J Am Coll Nutr. 1989;8:435.

133. Bittiner SB, Cartwright I, Tucker WFG, et al. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Lancet. 1988;1:378�380.

134. 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�1816.

135. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998;10:385�394.

136. Bassey EJ, Littlewood JJ, Rothwell MC, et al. Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of EfacalW v. calcium alone. Br J Nutr. 2000;83:629�635.

137. 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�466.

138. Clark WF, Parbtani A, Naylor CD, et al. Fish oil in lupus nephritis: clinical findings and methodological implications. Kidney Int. 1993;44:75�86.

139. Clark WF, Parbtani A. Omega-3 fatty acid supplementation in clinical and experimental lupus nephritis. Am J Kidney Dis. 1994;23:644�647.

140. Richardson AJ, Puri BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:233�239.

141. Voigt RG, Llorente AM, Jensen CL, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. 2001;139:189�196.

142. Harris WS. Dietary fish oil and blood lipids. Curr Opin Lipidol. 1996;7:3�7.

143. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 1994;90:2248�2257.

144. Harris WS. Dietary fish oil and blood lipids. Curr Opin Lipidol. 1996;7:3�7.

145. Montori VM, Farmer A, Wollan PC, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000;23:1407�1415.

146. Cobiac L, Clifton PM, Abbey M, et al. Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n�3 fatty acids in mildly hyperlipidemic males. Am J Clin Nutr. 1991;53:1210�1216.

147. Harris WS. Dietary fish oil and blood lipids. Curr Opin Lipidol. 1996;7:3�7.

148. 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;158:2071-2074.

149. Pradalier A, Bakouche P, Baudesson G, et al. Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo. Cephalalgia. 2001;21:818-822.

150. 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 Ther. 1997;11:485-491.

151. Yam D, et. al. The effect of omega-3 fatty acids on risk factors for cardiovascular diseases. Harefuah. 2001;140:1156-1158.

152. Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002;112:298-304.

153. Schmitz PG, McCloud LK, Reikes ST, et al. Prophylaxis of hemodialysis graft thrombosis with fish oil: double-blind, randomized, prospective trial. J Am Soc Nephrol. 2002;13:184-190.

154. Nemets B, Stahl Z, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry. 2002;159:477-479.

155. Vaddadi KS, Soosai E, Chiu E, et al. A randomised, placebo-controlled, double blind study of treatment of Huntington's disease with unsaturated fatty acids. Neuroreport. 2002;13:29-33.

156. Marchioli R, Barzi F, Bomba E, et al. 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 Miocardico (GISSI)-Prevenzione. Circulation. 2002;105:1897-1903.

157. Rudra PK, Krokan HE. Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaenoic acid. Anticancer Res. 2001;21(1A):29-38.

158. Hardman WE, Moyer MP, Cameron IL. Consumption of an omega-3 fatty acids product, INCELL AAFA, reduced side-effects of CPT-11 (irinotecan) in mice. Br J Cancer. 2002;86:983-988.

159. Middleton SJ, Naylor S, Woolner J, et al. A double-blind, randomized, placebo-controlled trial of essential fatty acid supplementation in the maintenance of remission of ulcerative colitis. Aliment Pharmacol Ther. 2002;16:1131-1135.

160. Mori TA, Burke V, Puddey IB, et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr. 2000;71:1085-1094.

161. Rambjor GS, Walen AI, Windsor SL Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids. 1996;31 Suppl:S45-49.

162. Agren JJ, Hanninen O, Julkunen A, et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur J Clin Nutr. 1996;50:765-771.

163. Childs MT, King IB, Knopp RH. Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid. Am J Clin Nutr. 1990;52:632-639.

164. Davidson MH, Maki KC, Kalkowski J, et al. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 1997;16:236-243.

165. Leigh-Firbank EC, Minihane AM, Minihane AM, et al. Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Br J Nutr. 2002;87:435-445.

166. Jacobs MN, Santillo D, Johnston PA, et al. Organochlorine residues in fish oil dietary supplements: comparison with industrial grade oils. Chemosphere. 1998;37:1709-1721.

167. Geleijnse JM, Giltay EJ, Grobbee DE, et al. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens. 2002;20:1493-1499.

168. 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;59:913-919.

169. Emsley R, Myburgh C, Oosthuizen P, et al. Randomized, placebo-controlled study of ethyl-eicosapentaenoic Acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002;159:1596-1598.

170. 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;158:2071-2074.

171. 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�865.

172. Harel Z, Gascon G, Riggs S, et al. Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. J Adolesc Health. 2002;31:154-161.

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

174. Geleijnse JM, Giltay EJ, Grobbee DE, et al. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens. 2002;20:1493-1499.

175. 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;59:913-919.

176. Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis. 2003;166:85�93.

177. Mangoni AA, Sherwood RA, Swift CG, et al. Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med. 2002;252:497�503.

178. Marchioli R, Schweiger C, Tavazzi L, et al. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lipids. 2001;36(Suppl):S119�S126.

179. Cleland L, James M, Proudman S. The role of fish oils in the treatment of rheumatoid arthritis. Drugs. 2003;63:845�853.

180. Zanarini MC, Frankenburg FR. Omega-3 Fatty Acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study. Am J Psychiatry. 2003;160:167�169.

181. Barber MD. Cancer cachexia and its treatment with fish-oil-enriched nutritional supplementation. Nutrition. 2001;17:751�755.

182. Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol. 2003;21:129�134.

183. Helland IB, Smith L, Saarem K, et al. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. 2003;111:E39�E44.

184. Smuts CM, Huang M, Mundy D, et al. Plasse T, Major S, Carlson SE. A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Obstet Gynecol. 2003;101:469�479.

185. Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet. 1992;339:1003�1007.

186. Blommers J, De Lange-De Klerk ES, Kuik DJ, et al. Evening primrose oil and fish oil for severe chronic mastalgia: A randomized, double-blind, controlled trial. Am J Obstet Gynecol. 2002;187:1389�1394.

187. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int. 2003;23:27�36.

188. Marangell LB, Martinez JM, Zboyan HA, et al. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry. 2003;160:996�998.