Main content

    Health Information

    Fish Oil & Cod Liver Oil (EPA & DHA)

    Fish Oil & Cod Liver Oil (EPA & DHA)

    Uses

    What Are Star Ratings?

    Our proprietary ?Star-Rating? system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

    For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

    3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

    2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

    1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

    This supplement has been used in connection with the following health conditions:

    Used for Why
    3 Stars
    Congestive Heart Failure
    850 to 882 mg per day
    Learn More

    In a double-blind study of patients with chronic heart failure, supplementation with the fatty acids present in fish oil for an average of four years resulted in a small but statistically significant decrease in the number of patients who died or were hospitalized for cardiovascular reasons. The treatment consisted of 850 to 882 mg per day of a mixture of eicosapentaenoic acid and docosahexaenoic acid (as their ethyl esters).1 In another double-blind trial, supplementation with eicosapentaenoic acid and docosahexaenoic acid improved heart function and decreased the number of hospitalizations in patients with heart failure due to dilated cardiomyopathy.2

    3 Stars
    High Triglycerides
    3,000 mg daily omega-3 fatty acids
    Learn More

    Many double-blind trials have demonstrated that fish oils (also called fish-oil concentrates) containing EPA and DHA (mentioned above) lower TG levels.3 The amount of fish oil used in much of the research was an amount that provided 3,000 mg per day of omega-3 fatty acids. To calculate how much omega-3 fatty acid is contained in a fish oil supplement, add together the amounts of EPA and DHA. For example, a typical 1,000-mg capsule of fish oil provides 180 mg of EPA and 120 mg of DHA (total omega-3 fatty acids equals 300 mg). Ten of these capsules would contain 3,000 mg of omega-3 fatty acids. Other sources of omega-3 fatty acids, such as flaxseed oil , do not lower TGs. While flaxseed oil has other benefits, it should not be used for the purpose of reducing TGs.

    Cod liver oil , another source of omega-3 fatty acids, has also been found to lower TGs.4 Cod liver oil is less expensive than the fish oil concentrates discussed previously. However, cod liver oil also contains relatively large amounts of vitamin A and vitamin D ; too much of either can cause side effects. In contrast, fish oil concentrates have little or none of these vitamins. Individuals wishing to use cod liver oil as a substitute for a fish-oil concentrate should consult a doctor.

    Omega-3 fatty acids from fish oil and cod liver oil have been reported to affect blood in many other ways that might lower the risk of heart disease .5 However, these supplements sometimes increase LDL cholesterol ?the bad form of cholesterol. A doctor can check to see if fish oil has this effect on an individual. Research shows that when 900 mg of garlic extract is added to fish oil, the combination still dramatically lowers TG levels but no longer increases LDL cholesterol.6 Therefore, it appears that taking garlic supplements may be a way to avoid the increase in LDL cholesterol sometimes associated with taking fish oil. People who take fish oil may also need to take vitamin E to prevent the oil from undergoing potentially damaging oxidation in the body.7 It is not known how much vitamin E is needed to prevent such oxidation. The amount required would presumably depend on the amount of fish oil used. In one clinical trial, 300 IU of vitamin E per day prevented oxidation damage in individuals taking 6 grams of fish oil per day.8

    3 Stars
    Hypertension
    3 to 15 grams daily omega-3 fatty acids
    Learn More

    EPA and DHA , the omega-3 fatty acids found in fish oil , lower blood pressure, according to an analysis of 31 trials.9 The effect was dependent on the amount of omega-3 fatty acids used, with the best results occurring in trials using unsustainably high levels: 15 grams per day?the amount often found in 50 grams of fish oil. Although results with lower intakes were not as impressive, trials using over 3 grams per day of omega-3 (as typically found in ten 1,000 mg pills of fish oil) also reported significant reductions in blood pressure. One double-blind trial reported that DHA had greater effects on blood pressure than EPA or mixed fish oil supplements.10 DHA is now available as a supplement separate from EPA.

    3 Stars
    Lupus
    Up to 20 grams fish oil per day after consultation with a doctor
    Learn More

    The omega-3 fatty acids in fish oil ?eicosapentaenoic acid (EPA) and docosahexaenoic acid ( DHA )?decrease inflammation. Supplementation with EPA and DHA has prevented autoimmune lupus in animal research.11 In a double-blind trial, 20 grams of fish oil daily combined with a low-fat diet led to improvement in 14 of 17 people with SLE in 12 weeks.12 Other studies also found that supplementing with 10 to 15 grams of fish oil per day,13 or with the amount of EPA and DHA provided by 10 grams per day of fish oil,14 is beneficial for people with SLE. People wishing to take such a large amount of fish oil should first consult with a doctor.

    3 Stars
    Rheumatoid Arthritis
    3 grams daily of EPA plus DHA
    Learn More

    Many double-blind trials have proven that omega-3 fatty acids in fish oil , called EPA and DHA , partially relieve symptoms of RA.15 , 16 , 17 , 18 , 19 , 20 , 21 The effect results from the anti-inflammatory activity of fish oil.22 Many doctors recommend 3 grams per day of EPA and DHA, an amount commonly found in 10 grams of fish oil. Positive results can take three months to become evident. In contrast, a double-blind trial found flaxseed oil (source of another form of omega-3 fatty acid) not to be effective for RA patients.23

    2 Stars
    Angina
    Consult a doctor
    Learn More

    Fish oil , which contains the fatty acids known as EPA and DHA , has been studied in the treatment of angina. In some studies, enough fish oil to provide a total of about 3 grams of EPA and 2 grams of DHA has reduced chest pain as well as the need for nitroglycerin;24 other investigators could not confirm these findings.25 People who take fish oil may also need to take vitamin E to protect the oil from undergoing potentially damaging oxidation in the body.26 It is not known how much vitamin E is needed to prevent such oxidation; the amount required would presumably depend on the amount of fish oil used. In one study, 300 IU of vitamin E per day prevented oxidation damage in individuals taking 6 grams of fish oil per day.27

    2 Stars
    Anxiety
    3 grams per day
    Learn More
    In a double-blind trial, fish oil was significantly more effective than a placebo in improving anxiety levels in a group of substance abusers (alcohol, cocaine, and/or heroin).28 The fish oil used in this study provided 3 grams per day of omega-3 fatty acids and was given for three months.
    2 Stars
    Asthma
    Consult a doctor
    Learn More

    Double-blind research shows that fish oil partially reduces reactions to allergens that can trigger attacks in some asthmatics.29 Another double-blind study showed that fish oil supplements prevented exercise-induced asthma attacks in people with asthma.30 A few other researchers have reported small but significant improvements when asthmatics supplement with fish oil,31 , 32 but reviews of the research concluded that most fish oil studies showed little or no benefit.33 , 34 It is possible that some of these trials failed to show an improvement because they did not last long enough to demonstrate an effect. There is evidence that children who eat oily fish may have a much lower risk of getting asthma.35 Moreover, in a double-blind trial, children who received 300 mg per day of fish oil (providing 84 mg of EPA and 36 mg of DHA) experienced significant improvement of asthma symptoms.36 It should be noted that these benefits were obtained under circumstances in which exposure to food allergens and environmental allergens was strictly controlled. Though the evidence supporting the use of fish oil remains somewhat conflicting, eating more fish and supplementing with fish oil may still be worth considering, especially among children with asthma.

    2 Stars
    Atherosclerosis
    3 to 6 grams fish oil daily, containing at least 30% omega-3 fatty acids
    Learn More

    Supplementation with fish oil , rich in omega-3 fatty acids, has been associated with favorable changes in various risk factors for atherosclerosis and heart disease in some,37 , 38 , 39 , 40 , 41 , 42 but not all, studies.43 , 44 , 45 A double-blind trial showed that people with atherosclerosis who took fish oil (6 grams per day for 3 months and then 3 grams a day for 21 months) had significant slowing of progression of atherosclerotic plaques and a decrease in cardiovascular events (for example, heart attack and stroke ) compared with those who did not take fish oil.46 These results contradict the findings of an earlier controlled trial in which fish oil supplementation for two years (6 grams per day) did not promote major favorable changes in the diameter of atherosclerotic coronary arteries.47

    2 Stars
    Bipolar Disorder
    Daily omega-3 fatty acids: 9.6 grams for adults, 1,290 to 4,300 mg for children
    Learn More

    People diagnosed with depression may have lower blood levels of omega-3 fatty acids.48 , 49 A double-blind trial found that bipolar patients taking 9.6 grams of omega-3 fatty acids from fish oil per day in addition to their conventional medications had significant improvements compared with those taking placebo.50 Similar benefits were reported in a preliminary trial that used 1.5 to 2 grams per day of pure eicosapentaenoic acid, a component of fish oil.51 In a preliminary trial, children with bipolar disorder saw benefits from omega-3 fatty acids (1,290 to 4,300 mg per day) from fish oil given for eight weeks.52

    2 Stars
    Breast-Feeding Support
    Consult a qualified healthcare practitioner
    [2 stars] Learn More

    Docosahexaenoic acid (DHA), an omega-3 fatty acid present in cod liver oil and other fish oils, is important for normal development of the brain and eyes. Studies have shown that higher concentrations of DHA in mothers? milk are associated with better visual acuity in the infants.53 Other studies have suggested that DHA improves the development of infants, although not all research agrees.54 Because DHA in the mother?s diet passes into the breast milk,55 some doctors advise nursing mothers to supplement their diet with cod liver oil or another fish-oil supplement. Women wishing to use this or any supplement while breast-feeding should consult their doctors and use only under the supervision of a qualified healthcare practitioner.

    2 Stars
    Cardiac Arrhythmia
    Do not take, or take only with a doctor's supervision, if there is a history of sustained ventricular tachycardia or ventricular fibrillation
    Learn More

    In a double-blind trial, people with a type of arrhythmia known as ventricular premature complexes were supplemented for 16 weeks with either 15 ml (1 tbsp) per day of fish oil or a similar amount of safflower oil as placebo. Patients taking the fish oil had a significantly reduced frequency of abnormal heartbeats compared with those receiving placebo, and 44% of those receiving fish oil experienced at least a 70% reduction in the frequency of abnormal beats.56 In a separate study, however, men given 20 ml (4 tsp) of cod liver oil per day for six weeks, beginning one week after a heart attack , had the same frequency of irregular heart beats as did men given no supplemental oil.57 In a double-blind study, people who had a history of certain potentially life-threatening arrhythmias?sustained ventricular tachycardia or ventricular fibrillation?had an increase in the recurrence rate of these arrhythmias when they took fish oil.58 A similar study found no adverse effect of fish oil supplements in people with these serious arrhythmias.59 Because of these conflicting findings, people with a history of either of these arrhythmias should consult a doctor before taking fish oil.

    2 Stars
    Crohn?s Disease
    2.7 grams daily omega-3 fatty acids in enteric-coated capsules
    Learn More

    Inflammation within the gut occurs in people suffering from Crohn?s disease. EPA and DHA , the omega-3 fatty acids found in fish oil , have anti-inflammatory activity. Though research is conflicting, there is some evidence that fish oil improves Crohn's disease symptoms. A two-year trial compared the effects of having people with Crohn?s disease eat 3.5 to 7 ounces of fish high in EPA and DHA per day or having them eat a diet low in fish.60 In that trial, the fish-eating group had a 20% relapse rate compared with 58% among those not eating fish. Salmon, herring, mackerel, albacore tuna, and sardines are all high in EPA and DHA.

    In a double-blind trial, people with Crohn?s disease who took supplements providing 2.7 g of EPA/DHA per day had a recurrence rate of 26% after one year, compared to a 59% recurrence rate among those taking placebo.61

    2 Stars
    Cystic Fibrosis
    2.7 grams of EPA daily
    Learn More

    The impaired digestion of fats in people with CF often leads to a deficiency of essential fatty acids. This deficiency may in turn lead to lowered immune function , which makes people with CF more susceptible to respiratory infection.62 This deficiency may be reversed by supplementation with corn oil (1 gram per 2.2 pounds body weight per day),63safflower oil (1 gram per 2.2 pounds body weight per day),64 linoleic acid (7.7 grams per day),65 and eicosapentaenoic acid (EPA from fish oil ) (2.7 grams per day).66 EPA supplementation was particularly effective. In a double-blind trial, six weeks of supplementation with 2.7 grams of EPA per day led to a reduction in sputum and improvement in lung function in children with chronic respiratory infection due to CF.67

    2 Stars
    Depression
    9.6 grams omega-3 fatty acids per day
    Learn More

    Omega-3 fatty acids found in fish oil , particularly DHA , are needed for normal nervous system function. Depressed people have been reported to have lower omega-3 fatty acid levels (for example, DHA) than people who are not depressed.68 , 69 , 70 , 71 Low levels of the other omega-3 fatty acid from fish, EPA, have correlated with increased severity of depression.72 In some double-blind trials, supplementation with various amounts of fish oil was beneficial for the treatment of depression in both children and adults,73 , 74 but fish oil was ineffective in other double blind trials.75 , 76

    EPA alone has also been reported to be beneficial. There is one case report of a man with a long history of severe depression who showed clear improvement within one month of starting a purified EPA supplement (4 grams per day of the ethyl ester of eicosapentaenoic acid [E-EPA]).77 In a double-blind study, supplementation with E-EPA for 12 weeks was significantly more effective than a placebo at relieving symptoms of depression.78 E-EPA was beneficial, even though the participants in the study had failed to respond adequately to conventional antidepressant drugs. The conventional medications were continued during treatment with E-EPA or placebo. An effective level of intake was 1 gram per day, whereas larger amounts of E-EPA resulted in little or no benefit. The authors of the study suggested that taking too much E-EPA might cause an imbalance with other essential fatty acids, which could reduce the effectiveness of the treatment.

    2 Stars
    Dysmenorrhea
    Refer to label instructions
    Learn More
    Diets low in omega-3 fatty acids (EPA and DHA ) have been associated with menstrual pain.79 In one double-blind trial, supplementation with fish oil , a good source of omega-3 fatty acids, led to a statistically significant 37% drop in menstrual symptoms. In that report, adolescent girls with dysmenorrhea took an unspecified amount of fish oil that provided 1,080 mg of EPA and 720 mg of DHA per day for two months to achieve this result.80 A double-blind trial found that the same amount of EPA and DHA plus 7.5 mcg per day of vitamin B12 led to a greater than 50% decrease in menstrual symptoms, but a group taking only fish oil did not obtain as much relief.81 Six grams of fish oil per day provides the approximate levels of EPA and DHA used in these trials. In another double-blind trial, 1 gram per day of fish oil significantly decreased pain intensity, compared with a placebo, in women with dysmennorhea.[REF]
    2 Stars
    Eczema
    Adults: 1,800 mg a day of EPA; children: proportionately less, according to body weight
    Learn More

    Ten grams of fish oil providing 1.8 grams of EPA (eicosapentaenoic acid) per day were given to a group of eczema sufferers in a double-blind trial. After 12 weeks, those using the fish oil experienced significant improvement.82 , 83 According to the researchers, fish oil may be effective because it reduces levels of leukotriene B4, a substance that has been linked to eczema.84 The eczema-relieving effects of fish oil may require taking ten pills per day for at least 12 weeks. Smaller amounts of fish oil have been shown to lack efficacy.85

    One trial using vegetable oil as the placebo reported that fish oil was barely more effective than the placebo (30% vs. 24% improvement).86 As vegetable oil had previously been reported to have potential therapeutic activity, the apparent negative outcome of this trial should not dissuade people with eczema from considering fish oil.

    2 Stars
    Epilepsy
    3.25 grams daily of omega-3 fatty acids
    Learn More

    In a preliminary study, supplementation with 3.25 grams per day of a mixture of omega-3 fatty acids (primarily eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) for six months markedly reduced the frequency of seizures in five severely retarded epileptic patients.87 Additional research is needed to confirm this report and to identify which people with epilepsy are most likely to benefit.

    2 Stars
    Heart Attack
    850 to, 1700 mg omega-3 fatty acids
    Learn More
    Fish oil contains the beneficial omega-3 fatty acids EPA and DHA , which have led to partial reversal of atherosclerosis in a double-blind trial.88 In another double-blind trial, individuals were given either fish oil (containing about 1 gram of EPA and 2/3 gram of DHA) or mustard oil (containing about 3 grams alpha linolenic acid, another omega-3 fatty acid) 18 hours after a heart attack. Both groups experienced fewer nonfatal heart attacks compared to a placebo group, while the fish oil group also experienced fewer fatal heart attacks.89 The largest published study on omega-3 fatty acids for heart attack prevention was the preliminary GISSI Prevenzione Trial,90 which reported that 850 mg of omega-3 fatty acids from fish oil per day for 3.5 years resulted in a 20% reduction in total mortality and a 45% decrease in sudden death. Other investigators suggest that fish oil reduces the amount of heart muscle damage from a heart attack and enhances the effect of blood-thinning medication.91 People wishing to supplement with fish oil should take fish oil supplements that include at least small amounts of vitamin E , which may protect this fragile oil against free radical damage.92
    2 Stars
    Immune Function and Critically Ill Patients
    Consult a qualified healthcare practitioner
    Learn More

    Research on the effect of the omega-3 fatty acids that are abundant in some fish, fish oils, and flaxseed oil is conflicting. Liquid diets containing omega-3 fatty acids used in hospitals for critically ill people have been shown to improve immune function and reduce infections.94 95 However, in one controlled study in healthy people, a low-fat diet improved or maintained immune function, but when fish was added to increase omega-3 fatty acid intake, immune function was significantly inhibited.96

    Supplementation with DHA (an omega-3 fatty acid found in fish oil) in healthy young men has been shown to decrease the activity of immune cells, such as natural killer (NK) cells, and to inhibit certain measures of inflammation in the test tube.97 The anti-inflammatory effects of DHA may be useful in the management of autoimmune disorders; however, such benefits need to be balanced with the potential for increased risk of infections. Other studies suggest that increased oxidative damage might be the reason for the negative effects on the immune system sometimes caused by fish oil, and that increased intake of antioxidants, such as vitamin E, could correct the problem.98

    2 Stars
    Immune Function and Post-Surgery Patients
    Refer to label instructions
     
    2 Stars
    Intermittent Claudication (Alpha-Linolenic Acid, Folic Acid, Oleic Acid, Vitamin B6, Vitamin E)
    200 mg of EPA and 130 mg of DHA daily, plus small amounts of vitamin B6, folic acid, vitamin E, oleic acid, and alpha-linolenic acid
    Learn More

    Men with intermittent claudication consumed a fortified milk product or regular milk daily for one year. The fortified product provided daily 130 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid (EPA and DHA, two fatty acids in fish oil ), small amounts of supplemental vitamin E , folic acid , and vitamin B6 , and additional amounts of oleic acid and alpha-linolenic acid. Compared with regular milk, the fortified milk product significantly increased the distance the participants could walk before the onset of pain .99

    2 Stars
    Macular Degeneration (Acetyl-L-Carnitine, Coenzyme Q10)
    Follow label directions
    Learn More

    In a double-blind study, supplementation with a proprietary blend of acetyl-L-carnitine , omega-3 fatty acids from fish oil , and coenzyme Q10 for 12 months resulted in an improvement in both visual function and in objective findings on eye examination (a decrease in the drusen-covered area on the retina).100

    2 Stars
    Multiple Sclerosis
    6 to 20 grams daily
    Learn More

    Although some doctors recommend fish oil capsules for people with MS, few investigations have explored the effects of this supplement. In one small trial, people with MS were given approximately 20 grams of fish oil in capsules per day.101 After one to four months, 42% of these people received slight but significant benefits, including reduced urinary incontinence and improved eyesight. However, a longer double-blind trial involving over 300 people with MS found that half this amount of fish oil given per day did not help.102A preliminary, two-year intervention trial tested the effects of fish oil supplements (5 ml of fish oil per day, providing 400 mg of EPA and 500 mg of DHA ) combined with other dietary supplements and dietary changes in people with newly diagnosed, relapsing-remitting MS.103 The other supplements included 3,333 IU of vitamin A per day, 400 IU of vitamin D per day, and approximately 5.5 IU of vitamin E per day. The dietary recommendations included reducing intake of sugar, coffee, tea, saturated fat from meat and dairy products, and alcohol, while increasing intake of fish, fruit, vegetables, and whole-grain bread. Sixty-nine percent of those following the regimen improved, 25% remained the same, and 6% (one person) deteriorated. The many interventions used in this trial make it impossible to determine what was responsible for the positive outcomes. Given the lack of other effective treatments for MS, though, this approach is worth trying while awaiting further evidence. In another trial, combining fish oil supplementation (6 grams per day) with a low-fat diet (15% of total calories) appeared to reduce the relapse rate in people with the relapsing-remitting form of MS.104

    In a small preliminary trial, people with MS were given 20 grams of cod liver oil , as well as approximately 680 mg of magnesium and 1,100 mg of calcium per day in the form of dolomite tablets.105 After one year, the average number of MS attacks decreased significantly for each person. Unlike fish oil capsules, the cod liver oil in this trial contained not only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), but 5,000 IU of vitamin D . Therefore, it is not known whether the vitamin D or fatty acids were responsible for the cod liver oil?s effects. (One preliminary study found that giving vitamin D-like drugs to animals with MS was helpful.)106 It is also possible that the magnesium and/or calcium given to these people reduced MS attacks. Magnesium107 and calcium108 levels have been reported to be lower in the nerve tissue of people with MS compared with healthy people.

    2 Stars
    Osteoporosis (Evening Primrose Oil)
    6 grams daily
    Learn More

    A preliminary trial found that elderly women with osteoporosis who were given 4 grams of fish oil per day for four months had improved calcium absorption and evidence of new bone formation.109 Fish oil combined with evening primrose oil (EPO) may confer added benefits. In a controlled trial, women received 6 grams of a combination of EPO and fish oil, or a matching placebo, plus 600 mg of calcium per day for three years.110 The EPO/fish oil group experienced no spinal bone loss in the first 18 months and a significant 3.1% increase in spinal bone mineral density during the last 18 months.

    2 Stars
    Phenylketonuria
    125 mg of oil or 15 mg of docosahexaenoic acid per 2.2 lbs (1 kg) of body weight daily
    Learn More
    The PKU diet is low in fatty acids, some of which are essential for proper brain development.111 In one controlled study of children with PKU who were deficient in fatty acids, supplementation with fish oil (but not with black currant seed oil) for six months improved the deficiency. The children received 500 mg of oil per 8.8 pounds of body weight each day for 6 months. The amount varied from 5?8 capsules (each containing 500 mg) per day for each child.112 In another study, fish oil supplementation (providing 15 mg of docosahexaenoic acid per 2.2 pounds of body weight per day) improved body coordination and fine motor skills in children with PKU.113
    2 Stars
    Pre- and Post-Surgery Health
    3.3 to 5 grams daily omega-3 fatty acids before and after surgery
    Learn More

    Omega-3 fatty acids have anti-inflammatory properties,114 and animal studies suggest that supplementation with omega-3 fatty acids may improve recovery and prevent infection after surgery.115 , 116 A controlled human trial found that intravenous nutritional formulas containing omega-3 fatty acids given post-operatively lowered the production of inflammatory chemicals compared with standard nutritional formulas.117 Other human studies of omega-3 fatty acid-supplemented nutritional formulas used in surgery patients have included other supplemental nutrients as well and are discussed below.118

    2 Stars
    Pregnancy and Postpartum Support
    2.7 to 6.1 mg daily of omega-3 fatty acids (EPA plus DHA)
    Learn More

    Supplementation with fish oil (providing either 2.7 g or 6.1 g per day of the omega-3 fatty acids EPA and DHA ) significantly reduced recurrence of premature delivery, according to data culled from six clinical trials involving women with a high risk for such complications.119 Fish oil supplementation did not prevent premature delivery of twin pregnancies, nor did it have any preventive effect against intrauterine growth retardation or pregnancy-induced hypertension. Fish oils should be free of contaminants, such as mercury and organochlorine pesticides. Women who eat substantial amounts of certain types of seafood (e.g., swordfish, tuna) may be consuming contaminants that can increase the risk of brain and nervous system abnormalities in their offspring. Exposure to mercury and polychlorinated biphenyls (PCBs) was found to be increased in relation to maternal intake of seafood. Higher exposure to these toxic contaminants has been linked to an increased risk of deficits in the developing brains and nervous systems of the children.120

    2 Stars
    Pregnancy and Prenatal Growth
    Refer to label instructions
    Learn More
    The DHA found in fish oil is essential for the development of the visual system in infants.121 In one double-blind study, 103 term infants were randomly assigned to receive either formula with no docosahexaenoic acid (DHA) or arachidonic acid (ARA) or formula supplemented with DHA and ARA at concentrations similar to those found in human milk, starting when they were six days old. Visual maturation was assessed by measuring sweep visual evoked potential at ages 6, 17, 26, and 52 weeks. At each age, the supplemented group measured better, which led researchers to conclude that long-term supplementation of infant formula with DHA and ARA in amounts typical in human milk may help enhance visual development during the first year of life.
    2 Stars
    Psoriasis
    Take orally 10 grams daily oil or 3.6 grams daily EPA, or apply a 10% topical solution twice per day
    Learn More

    In a double-blind trial, fish oil (10 grams per day) was found to improve the skin lesions of psoriasis.122 In another trial, supplementing with 3.6 grams per day of purified eicosapentaenoic acid (EPA, one of the fatty acids found in fish oil) reduced the severity of psoriasis after two to three months.123 , 124 That amount of EPA is usually contained in 20 grams of fish oil, a level that generally requires 20 pills to achieve. However, when purified EPA was used in combination with purified docosahexaenoic acid ( DHA , another fatty acid contained in fish oil), no improvement was observed.125

    Additional research is needed to determine whether fish oil itself or some of its components are more effective for people with psoriasis. One trial showed that applying a preparation containing 10% fish oil directly to psoriatic lesions twice daily resulted in improvement after seven weeks.126 In addition, promising results were reported from a double-blind trial in which people with chronic plaque-type psoriasis received 4.2 g of EPA and 4.2 g of DHA or placebo intravenously each day for two weeks. Thirty-seven percent of those receiving the essential fatty acid infusions experienced greater than 50% reduction in the severity of their symptoms.127

    Supplementing with fish oil also may help prevent the increase in blood levels of triglycerides that occurs as a side effect of certain drugs used to treat psoriasis (e.g., etretinate and acitretin).128

    2 Stars
    Raynaud?s Disease
    4 grams of EPA per day
    Learn More

    In a double-blind trial, supplementation with 12 large capsules of fish oil per day (providing 4 grams of eicosapentaenoic acid [EPA] per day) for 6 or 12 weeks reduced the severity of blood-vessel spasm in 5 of 11 people with Raynaud?s phenomenon.129 Fish oil was effective in people with primary Raynaud?s disease, but not in those whose symptoms were secondary to another disorder.

    2 Stars
    Schizophrenia
    2,000 to 3,000 mg daily of EPA
    Learn More

    There are two different classes of essential fatty acids: omega-6 fatty acids and omega-3 fatty acids . There is considerable evidence these fatty acids are deficient, or are not used properly, in people with schizophrenia.130 , 131 , 132 , 133 , 134 , 135 Some investigators suggest this altered fatty acid metabolism may be involved in the increased need for niacin seen in some schizophrenic patients.136 A case has been reported in which a man with schizophrenia had dramatic and sustained improvement while being supplemented with 2 grams daily of omega-3 fatty acids.137 In a preliminary trial, schizophrenic patients receiving omega-3 fatty acids showed improvement in symptoms, as well as a reduction in adverse effects from their anti-psychotic medications.138 Another study found that people with schizophrenia had lower blood levels of both omega-3 and omega-6 fatty acids, compared with non-schizophrenic people, even though both groups were consuming similar amounts of these fatty acids.139 In a separate preliminary study, higher intake of omega-3 fatty acids was associated with less severe disease, and supplementation with 10 grams of concentrated fish oil , a source of omega-3 fatty acids, led to significant improvement in symptoms over a six-week period.140 In addition, a double-blind trial found that supplementing with 1.2 g per day of omega-3 fatty acids from fish oil prevented the development of psychosis in adolescents and young adults who were at very high risk of developing a psychotic disorder.141

    In a double-blind trial that included 87 patients with chronic schizophrenia or a related illness (schizoaffective disorder), supplementation with 3 grams per day of eicosapentaenoic acid (one of the omega-3 fatty acids found in fish oil) was ineffective.142 The patients in this negative study were older and had been ill for longer, compared with patients in earlier studies who improved with omega-3 fatty acid supplementation.

    Several clinical trials have examined the effects of supplementation with essential fatty acids in people with schizophrenia, with inconsistent results.143 , 144 , 145 , 146 While the results of trials using omega-3 fatty acids are promising, further double-blind trials are needed to establish whether fatty acid supplementation is an effective therapy for schizophrenia. Trials of omega-6 fatty acids (like GLA from borage oil) have yielded predominantly negative results.147

    2 Stars
    Sickle Cell Anemia
    250 mg of oil per 2.2 lbs (1 kg) of body weight daily
    Learn More

    In a preliminary trial, 13 patients with sickle cell anemia were given two supplement combinations for seven to eight months each. The first combination included 109 mg zinc , 153 IU vitamin E , 600 mg vitamin C , and 400 ml (about 14 ounces) of soybean oil containing 11 grams of linoleic acid and 1.5 grams of alpha linolenic acid. The second combination included 140 IU vitamin E, 600 mg vitamin C, and 20 grams of fish oil containing 6 grams of omega-3 fatty acids. Reduction in diseased cells was observed only during the administration of the first protocol. The authors concluded that zinc was the important difference between the two combinations and may be a protector of red blood cell membranes.148

    Fish oil alone has also been studied. In a double-blind trial, supplementation with menhaden oil, in the amount of 250 mg per 2.2 pounds of body weight per day for one year, reduced the frequency of severe pain episodes by approximately 45%, compared with placebo.149 This treatment may work by correcting an imbalance between omega-3 and omega-6 fatty acids that occurs in people with sickle cell anemia.150 The beneficial effect of the omega-3 fatty acids present in fish oil was confirmed in another double-blind study.151

    2 Stars
    Tooth Decay
    3 tsp per day of cod liver oil
    Learn More

    One older controlled trial found that children given 3 teaspoons of cod liver oil per day (containing roughly 800 IU of vitamin D ) for an entire school year had over 50% fewer new cavities.152 These promising results have not been followed up with modern placebo-controlled trials.

    2 Stars
    Ulcerative Colitis
    5.4 grams daily of omega-3 fatty acids
    Learn More

    Preliminary153 and double-blind trials154 , 155 , 156 have found that fish oil supplementation reduces inflammation, decreases the need for anti-inflammatory drugs, and promotes normal weight gain in people with UC. However, fish oil has not always been effective in clinical trials for UC.157 Amounts used in successful clinical trials provided 3.2 grams of EPA and 2.2 grams of DHA per day?the two important fatty acids found in fish oil.

    In a preliminary trial, people with UC significantly improved on a sugar-free, low-allergen diet with additional nutritional supplementation that included a multivitamin-mineral supplement (2?6 tablets per day); a fish oil supplement (400 mg per day); borage oil (400 mg per day); flaxseed oil (400 mg per day); and a probiotic formula containing Lactobacillus acidophilus and other species of beneficial bacteria.158 Some participants received slight variations of this regimen. Since so many different supplements were given and since the trial was not controlled, it is not possible to say which, if any, of the nutrients was responsible for the improvement observed by the researchers.

    1 Star
    Alzheimer?s Disease
    Refer to label instructions
    Learn More

    In a double-blind trial, supplementing with the fatty acids present in fish oil (0.6 grams per day of EPA and 1.7 grams per day of DHA) for six months was not beneficial in people with Alzheimer's disease. However, in the subgroup of people with very mild cognitive impairment, supplementation with these fatty acids slowed the rate of cognitive decline compared with a placebo.159

    1 Star
    Chronic Fatigue Syndrome
    Refer to label instructions
    Learn More

    In a preliminary study, four patients with chronic fatigue syndrome reported an improvement in their symptoms after taking an essential fatty acid supplement daily for at least 12 weeks.160 The amount used was 10 to 18 capsules per day, and each capsule contained 93 mg of eicosapentaenoic acid (EPA), 29 mg of docosahexaenoic acid (DHA), and 10 mg of gamma-linolenic acid. Because there was no placebo group in this study and, because fatigue often improves after treatment with a placebo, additional research is needed to confirm this report.

    1 Star
    Chronic Obstructive Pulmonary Disease
    Refer to label instructions
    Learn More

    A greater intake of the omega-3 fatty acids found in fish oils has been linked to reduced risk of COPD,161 though research has yet to investigate whether fish oil supplements would help people with COPD. In a double-blind trial, people with COPD received a fatty acid supplement (providing daily 760 mg of gamma-linolenic acid, 1,200 mg of alpha-linolenic acid, 700 mg of eicosapentaenoic acid, and 340 mg of docosahexaenoic acid) or a placebo (80% palm oil and 20% sunflower oil) during an eight-week rehabilitation program. Compared with the placebo, the fatty acid supplement significantly improved exercise capacity.162 While two of the fatty acids supplied in this supplement (eicosapentaenoic acid [EPA] and docosahexaenoic [DHA] acid) are found in fish oil, is not known which components of the supplement were most responsible for the improvement. Gamma-linolenic acid is found in evening primrose oil , black currant seed oil, and borage oil; alpha-linolenic acid is found in flaxseed oil and other oils.

    1 Star
    Colon Cancer
    Refer to label instructions
    Learn More
    Several human studies have found that supplementation with omega-3 fatty acids from fish oil leads to a reduction in markers for the risk of colon cancer.163 , 164 , 165 In each case, enough fish oil was supplemented to supply several grams of omega-3 fatty acids per day, though the optimal amount remains unknown.
    1 Star
    Endometriosis
    Refer to label instructions
    Learn More

    Animal research suggests that fish oils may reduce the severity of endometriosis,166 , 167 and fish oils have been shown to improve symptoms of dysmenorrhea (painful menstruation),168 which may be caused by endometriosis. Therefore, while no specific research has been done on the effects of fish oils in women with endometriosis, some health practitioners recommend several grams of fish oil per day for this condition.

    1 Star
    Glaucoma
    Refer to label instructions
    Learn More

    Surveys have shown that Inuit people, who consume large amounts of omega-3 fatty acids, have a much lower incidence of some types of glaucoma than do Caucasians. Although there have been no studies on the use of omega-3 fatty acids to treat glaucoma, one study found that cod liver oil (a rich source of omega-3 fatty acids) reduced intraocular pressure in animals.169

    1 Star
    Macular Degeneration
    Refer to label instructions
    Learn More
    An assessment of 3,654 Australians aged 49 years or older found an association between a diet high in omega-3 fatty acids from fish and a lower risk of age-related macular degeneration.170
    1 Star
    Migraine Headache
    Refer to label instructions
    Learn More

    Fish oil containing EPA and DHA has been reported to reduce the symptoms of migraine headache in a double-blind trial using 1 gram of fish oil per 10 pounds of body weight.171 , 172 Fish oil may help because of its effects in modifying prostaglandins (hormone-like substances made by the body).

    1 Star
    Osteoarthritis
    Refer to label instructions
    Learn More

    The omega-3 fatty acids present in fish oil , EPA and DHA , have anti-inflammatory effects and have been studied primarily for rheumatoid arthritis , which involves significant inflammation. However, osteoarthritis also includes some inflammation.173 In a 24-week controlled but preliminary trial studying people with osteoarthritis, people taking EPA had ?strikingly lower? pain scores than people who took placebo.174 However, in a double-blind trial by the same research group, supplementation with 10 ml of cod liver oil per day was no more effective than a placebo.175

    1 Star
    Osteoporosis
    Refer to label instructions
    Learn More

    A preliminary trial found that elderly women with osteoporosis who were given 4 grams of fish oil per day for four months had improved calcium absorption and evidence of new bone formation.176 Fish oil combined with evening primrose oil (EPO) may confer added benefits. In a controlled trial, women received 6 grams of a combination of EPO and fish oil, or a matching placebo, plus 600 mg of calcium per day for three years.177 The EPO/fish oil group experienced no spinal bone loss in the first 18 months and a significant 3.1% increase in spinal bone mineral density during the last 18 months.

    1 Star
    Photosensitivity
    redundant
    Learn More

    In a small preliminary trial, supplementation with fish oil (10 grams per day for three months) reduced photosensitivity in 90% of people suffering from polymorphous light eruptions.178

    1 Star
    Preeclampsia
    Refer to label instructions
    Learn More

    Fish oil supplementation has been proposed to lower the incidence of preeclampsia.179 , 180 However, controlled clinical trials suggest that fish oil does not reduce symptoms181 or protect against preeclampsia.182 , 183

    1 Star
    Type 1 Diabetes
    Refer to label instructions
    Learn More
    Glucose tolerance improves in healthy people taking omega-3 fatty acid supplements.184 And in one trial, people with diabetic nerve damage (neuropathy) and diabetic nephropathy experienced significant improvement when given 600 mg three times per day of purified eicosapentaenoic acid (EPA)?one of the two major omega-3 fatty acids found in fish oil supplements?for 48 weeks.185 However, controlled studies have found that fish oil supplementation increases cholesterol in people with type 1 diabetes.186 , 187 Until the risk?benefit ratio of using fish oil is clarified, people with diabetes should feel free to increase their fish intake, but they should consult a doctor before taking fish oil supplements.
    1 Star
    Type 2 Diabetes
    Refer to label instructions
    Learn More
    Glucose tolerance improves in healthy people taking omega-3 fatty acid supplements,188 and some studies have found that fish oil supplementation also improves glucose tolerance,189 high triglycerides ,190 and cholesterol levels in people with type 2 diabetes.191 And in one trial, people with diabetic neuropathy and diabetic nephropathy experienced significant improvement when given 600 mg three times per day of purified eicosapentaenoic acid (EPA)?one of the two major omega-3 fatty acids found in fish oil supplements?for 48 weeks.192 However, other studies have found that type 2 diabetes worsens with fish oil supplementation.193 , 194 , 195 , 196 Until this issue is resolved, people with diabetes should feel free to eat fish, but they should consult a doctor before taking fish oil supplements.

    How It Works

    How to Use It

    Presumably, healthy people who frequently eat fatty fish (several times per week) have no need to supplement with fish oil. How much EPA and DHA , if any, should be supplemented by healthy people who do not eat much fatty fish, remains unclear.

    Most researchers studying the effects of EPA and DHA in humans who have a variety of health conditions have given those people at least 3 grams of the total of EPA plus DHA?an amount that may require 10 grams of fish oil, because most fish oil contains only 18% EPA and 12% DHA.

    The health benefits for people with Crohn?s disease have been reported with a special, enteric-coated preparation of purified EPA/DHA manufactured from fish oil. This preparation of purified fatty acids does not cause the gastrointestinal symptoms that often result from taking regular fish oil supplements, which makes it a peferable source of EPA/DHA for people with gastrointestinal illnesses.197

    In one trial, the maximum amount of fish oil tolerated by people being treated for cancer-related weight loss was reported to be approximately 21 grams per day.198 However, in people who do not have cancer, the maximum tolerated amount may be different.

    Where to Find It

    EPA and DHA are found in mackerel, salmon, herring, sardines, sablefish (black cod), anchovies, albacore tuna, and wild game. Cod liver oil contains large amounts of EPA and DHA. Fish oil supplements typically contain 18% EPA and 12% DHA, though more purified (i.e., higher in EPA and DHA) fish oil supplements are sometimes available. In addition, DHA is available in a supplement that does not contain significant amounts of EPA.

    Possible Deficiencies

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

    At least four studies have reported a reduced blood level of omega-3 fatty acids in people with depression .199 , 200 , 201 , 202

    People with rheumatoid arthritis have been found to have decreased levels of omega-3 fatty acids, such as are found in fish oil, in their joint fluid and blood.203

    Interactions

    Interactions with Supplements, Foods, & Other Compounds

    Some evidence suggests that adding vitamin E to fish oil may prevent fish oil-induced increase in blood sugar levels.204

    People who took fish oil and who also took 15 grams of pectin per day were reported to have reductions in LDL cholesterol .205 This suggests that pectin may overcome the occasional problem of increased LDL cholesterol reported in people who supplement with fish oil. The LDL-cholesterol raising effect of EPA and DHA has also been reported to be prevented by taking garlic supplements (or presumably including garlic in the diet) along with EPA and DHA.206

    Interactions with Medicines

    Certain medicines interact with this supplement.

    Types of interactions: Beneficial Adverse Check

    Replenish Depleted Nutrients

    • none

    Reduce Side Effects

    • Paclitaxel
      In a double-blind study, supplementing with the omega-3 fatty acids present in fish oil decreased the incidence of drug-induced nerve damage (peripheral neuropathy) in women receiving paclitaxel for breast cancer. The amounts used were 540 mg of DHA (docosahexaenoic acid) and 100 mg of EPA (eicosapentaenoic acid), each three times per day.211
      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ribavirin
      Anemia is one of the side effects of ribavirin therapy. In a preliminary trial, supplementing with EPA partially prevented the decline in hemoglobin levels in patients with hepatitis C who were being treated with the combination of ribavirin and pegylated interferon alpha-2b.213

    Support Medicine

    • Atorvastatin

      In a preliminary trial, taking an HMG-CoA reductase inhibitor (?statin?) for about three years significantly lowered triglyceride levels and raised levels of HDL (?good?) cholesterol in people with high cholesterol who had also been supplementing with either 900 mg or 1,800 mg of EPA for three months.207 The authors of the study concluded that the combination of the statin and EPA may prevent coronary heart disease better than the drug alone. Since drugs in the statin family have similar mechanisms of action, people taking any statin drug may benefit from fish oil.

    • Citalopram
      In patients with major depression, the addition of the omega-3 fatty acids present in fish oil (1.8 g per day of eicosapentaenoic acid and 0.4 g per day of docosahexaenoic acid, in 2 divided amounts per day for 8 weeks) enhanced the antidepressant effect of citalopram.208
      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Fluvastatin

      In a preliminary trial, taking an HMG-CoA reductase inhibitor (?statin?) for about three years significantly lowered triglyceride levels and raised levels of HDL (?good?) cholesterol in people with high cholesterol who had also been supplementing with either 900 mg or 1,800 mg of EPA for three months.209 The authors of the study concluded that the combination of the statin and EPA may prevent coronary heart disease better than the drug alone. Since drugs in the statin family have similar mechanisms of action, people taking any statin drug may benefit from fish oil.

    • Lovastatin

      In a preliminary trial, taking an HMG-CoA reductase inhibitor (?statin?) for about three years significantly lowered triglyceride levels and raised levels of HDL (?good?) cholesterol in people with high cholesterol who had also been supplementing with either 900 mg or 1,800 mg of EPA for three months.210 The authors of the study concluded that the combination of the statin and EPA may prevent coronary heart disease better than the drug alone. Since drugs in the statin family have similar mechanisms of action, people taking any statin drug may benefit from fish oil.

    • Pravastatin

      In a preliminary trial, taking an HMG-CoA reductase inhibitor (?statin?) for about three years significantly lowered triglyceride levels and raised levels of HDL (?good?) cholesterol in people with high cholesterol who had also been supplementing with either 900 mg or 1,800 mg of EPA for three months.212 The authors of the study concluded that the combination of the statin and EPA may prevent coronary heart disease better than the drug alone. Since drugs in the statin family have similar mechanisms of action, people taking any statin drug may benefit from fish oil.

    • Rosuvastatin

      In a preliminary trial, taking an HMG-CoA reductase inhibitor (?statin?) for about three years significantly lowered triglyceride levels and raised levels of HDL (?good?) cholesterol in people with high cholesterol who had also been supplementing with either 900 mg or 1,800 mg of EPA for three months.214 The authors of the study concluded that the combination of the statin and EPA may prevent coronary heart disease better than the drug alone. Since drugs in the statin family have similar mechanisms of action, people taking any statin drug may benefit from fish oil.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Simvastatin

      The omega-3 fatty acid EPA, present in fish oil , may improve the cholesterol- and triglyceride -lowering effect of simvastatin. In a preliminary trial, people with high cholesterol who had been taking simvastatin for about three years were able to significantly lower their triglyceride levels and raise their levels of HDL (?good?) cholesterol by supplementing with either 900 mg or 1800 mg of EPA for three months in addition to simvastatin.215 The authors of the study concluded that the combination of simvastatin and EPA may prevent coronary heart disease better than simvastatin alone.

    Reduces Effectiveness

    • none

    Potential Negative Interaction

    • none

    Explanation Required

    • none

    The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers? package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

    Side Effects

    Side Effects

    While those with heart disease and diabetes have often been reported to benefit from supplementation with fish oil,216 , 217 both groups should check with their doctor before taking more than 3 grams of fish oil per day for several months. Elevations in blood sugar and cholesterol levels may occur in some people who take fish oil.218

    The increase in blood sugar appears to be related in part to the amount of fish oil used.219 The impairment of sugar metabolism sometimes caused by supplementation with fish oil has been prevented by the addition of half an hour of moderate exercise three times a week.220

    While supplementation with fish oil consistently lowers triglycerides , the effect of fish oil on LDL (?bad?) cholesterol varies, and in some people, fish oil supplementation has been reported to increase LDL levels.221

    There has been one case report in which a woman with a known allergy to crabs developed a severe allergic reaction after ingesting fish oil.222

    References

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

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

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

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

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

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

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

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

    9. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 1993;88:523?33.

    10. 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?60.

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

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

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

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

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

    16. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthrit Rheum 1990;33(6):810?20.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    48. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31 Suppl:S157?61.

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

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

    51. Osher Y, Bersudsky Y, Belmaker RH. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry 2005;66:726?9.

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

    53. Jorgensen MH, Hernell O, Hughes E, Michaelsen KF. Is there a relation between docosahexaenoic acid concentration in mothers? milk and visual development in term infants? J Pediatr Gastroenterol Nutr 2001;32:293?6.

    54. Gibson RA, Makrides M. Long-chain polyunsaturated fatty acids in breast milk: are they essential? Adv Exp Med Biol 2001;501:375?83.

    55. Harris WS, Connor WE, Lindsey S. Will dietary w-3 fatty acids change the composition of human milk? Am J Clin Nutr 1984;40:780?5.

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

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

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

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

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

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

    62. Chase HP, Dupont J. Abnormal levels of prostaglandins and fatty acids in blood of children with cystic fibrosis. Lancet 1978;2:236?8.

    63. Rosenlund ML, Selekman JA, Kim HK, Kritchevsky D. Dietary essential fatty acids in cystic fibrosis. Pediatrics 1977;59:428?32.

    64. Lloyd-Still JD, Simon SH, Wessel HU, Gibson LE. Intravenous linoleic acid supplementation in children with cystic fibrosis. Pediatrics 1979;64:50?2.

    65. Chase HP, Dupont J. Abnormal levels of prostaglandins and fatty acids in blood of children with cystic fibrosis. Lancet 1978;2:236?8.

    66. Lawrence R, Sorrell T. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenic role for leukotriene B4. Lancet 1993;342:465?9.

    67. Lawrence R, Sorrell T. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenic role for leukotriene B4. Lancet 1993;342:465?9.

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

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

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

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

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

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

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

    75. Grenyer BFS, Crowe T, Meyer B, et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2007;31:1393?6.

    76. Rogers PJ, Appleton KM, Kessler D, et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 2008;99:421?31.

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

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

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

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

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

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

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

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

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

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

    87. Schlanger S, Shinitzky M, Yam D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia 2002;43:103?104.

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

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

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

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

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

    93. Huang T, Zheng J, Chen Y, et al. High consumption of omega-3 polyunsaturated fatty acids decrease plasma homocysteine: a meta-analysis of randomized, placebo-controlled trials. Nutrition 2011;27:863?7.

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

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

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

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

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

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

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

    101. Cendrowski W. Multiple sclerosis and MaxEPA. Br J Clin Pract 1986;40:365?7.

    102. Bates D, Cartlidge NE, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 1989;52:18?22.

    103. Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand 2000;102:143?9.

    104. Weinstock-Guttman B, Baier M, Park Y, et al. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids 2005;73:397?404.

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

    106. DeLuca HF, Zierold C. Mechanisms and functions of vitamin D. Nutr Rev 1998;56(2 Pt 2):S4?10 [review].

    107. Yasui M, Yase Y, Ando K, et al. Magnesium concentration in brains from multiple sclerosis patients. Acta Neurol Scand 1990;81:197?200.

    108. Yasui M, Ota K. Experimental and clinical studies on dysregulation of magnesium metabolism and the aetiopathogenesis of multiple sclerosis. Magnes Res 1992;5:295?302.

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

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

    111. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132?5.

    112. Agostoni C, Riva E, Biasucci G, et al. The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children. Prostaglandins Leukot Essent Fatty Acids 1995;53:401?4.

    113. Beblo S, Reinhardt H, Demmelmair H, et al. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr 2007;150:479?84.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    141. Amminger GP, Schafer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 2010;67:146?54.

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

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

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

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

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

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

    148. Muskiet FA, Muskiet FD, Meiborg G, Schermer JG. Supplementation of patients with homozygous sickle cell disease with zinc, alpha-tocopherol, vitamin C, soybean oil, and fish oil. Am J Clin Nutr 1991;54:736?44.

    149. 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?74.

    150. 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?74.

    151. Daak AA, Ghebremeskel K, Hassan Z, et al. Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. <em>Am J Clin Nutr</em> 2013;97:37?44.

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

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

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

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

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

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

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

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

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

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

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

    163. Bartram H-P, Gostner A, Kelber E, et al. Effects of fish oil on fecal bacterial enzymes and steroid excretion in healthy volunteers: implications for colon cancer prevention. Nutr Cancer 12996;25:71?8.

    164. Huang Y-C, Jessup JM, Forse RA, et al. n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa. Lipids 1996;31:S313?7.

    165. Anti M, Armelaoe F, Marra G, et al. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 1994;107:1709?18.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    184. Zak A, Zeman M, Hrabak P, et al. Changes in the glucose tolerance and insulin secretion in hypertriglyceridemia: effects of dietary n-3 fatty acids. Nutr Rep Int 1989;39:235?42.

    185. Okuda Y, Mizutani M, Ogawa M, et al. Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications 1996;10:280?7.

    186. Mori TA, Vandongen R, Masarei JR, et al. Comparison of diets supplemented with fish oil or olive oil on plasma lipoproteins in insulin-dependent diabetics. Metabolism1991;40:241?6.

    187. Mori TA, Vandongen R, Masarei JR. Fish oil-induced changes in apolipoproteins in IDDM subjects. Diabetes Care 1990;13:725?32.

    188. Zak A, Zeman M, Hrabak P, et al. Changes in the glucose tolerance and insulin secretion in hypertriglyceridemia: effects of dietary n-3 fatty acids. Nutr Rep Int 1989;39:235?42.

    189. Popp-Snijders C, Schouten JA, Heine RJ, et al. Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. Diabetes Res 1987;4:141?7.

    190. Albrink MJ, Ullrich IH, Blehschmidt NG, et al. The beneficial effect of fish oil supplements on serum lipids and clotting function of patients with type II diabetes mellitus. Diabetes 1986;35 (suppl 1):43A [abstract #172].

    191. Wei I, Ulchaker M, Sheehan J. Effect of omega-3 fatty acids (FA) in non-obese non-insulin dependent diabetes (NIDDM). Am Clin Nutr 1988;47:775 [abstract #70].

    192. Okuda Y, Mizutani M, Ogawa M, et al. Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications 1996;10:280?7.

    193. Vandongen R, Mori TA, Codde JP, et al. Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients. Med J Aust 1988;148:141?3.

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

    195. Stackpoole PW, Alig J, Kilgore LL, et al. Lipodystrophic diabetes mellitus. Investigations of lipoprotein metabolism and the effects of omega-3 fatty acid administration in two patients. Metabolism 1988;37:944?51.

    196. Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med 1988;108:663?8.

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

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

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

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

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

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

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

    204. Luostarinen R, Wallin R, Wibell L, et al. Vitamin E supplementation counteracts the fish oil-induced increase of blood glucose in humans. Nutr Res 1995; 15:953?68.

    205. Sheehan JP, Wei IW, Ulchaker M, Tserng KY. Effect of high fiber intake in fish oil-treated patients with non-insulin-dependent diabetes mellitus Am J Clin Nutr 1997; 66:1183?7.

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

    207. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

    208. Gertsik L, Poland RE, Bresee C, Rapaport MH. Omega-3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder. J Clin Psychopharmacol 2012 Feb;32:61.

    209. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

    210. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

    211. Ghoreishi Z, Esfahani A, Djazayeri A, et al. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer2012;12:355.

    212. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

    213. Suzuki M, Inage E, Minowa K, et al. Prophylaxis for ribavirin-related anemia using eicosapentaenoic acid in chronic hepatitis C patients. Pediatr Int 2012;54:528?31.

    214. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

    215. Nakamura N, Hamazaki T, Ohta M, et al. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29:22?5.

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

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

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

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

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

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

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

    This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.

    Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.