-------------------------------------------------------------------------------- Requirements/Sources There is no daily requirement for fish oil. However, a healthy diet should provide at least 5 g of essential fatty acids daily. Many grains, fruits, vegetables, and vegetable oils contain significant amounts of essential omega-6 and/or omega-3 fatty acids. Some authorities believe that it is important to consume several times more omega-3 fatty acids than omega-6 fatty acids. If this theory is true, taking fish oil supplements might help ensure the proper balance. Cod liver oil is the most common form of fish oil, but it may not be the best for reasons of safety (see Safety Issues). Salmon oil, mackerel oil, halibut oil, and the oils from other coldwater fish might be better choices. -------------------------------------------------------------------------------- Therapeutic Dosages Typical dosages of fish oil are 3 to 9 g daily, but this is not the upper limit. In one study, participants ingested 60 g daily. The most important omega-3 fatty acids found in fish oil are called EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). In order to match the dosage used in several major studies, you should probably take enough fish oil to supply about 1.8 g of EPA (1,800 mg) and 0.9 g of DHA daily (900 mg). Far higher doses have been used in studies, as well. Some manufacturers add vitamin E to fish oil capsules to keep the oil from becoming rancid. Another method is to remove all the oxygen from the capsule. If possible, purchase fish oil products certified as free of significant levels of toxic organochlorines and PCBs (see Safety Issues). Flaxseed oil also contains omega-3 fatty acids, although of a different kind. It has been suggested as a less smelly substitute for fish oil. However, flaxseed oil does not appear to be therapeutically equivalent to fish oil.1 -------------------------------------------------------------------------------- Therapeutic Uses There has been a great deal of excitement about the possibility of using fish oil to help prevent heart disease. According to some but not all studies, fish or fish oil appears to lower triglyceride levels, raise HDL ("good") cholesterol, "thin" the blood, reduce levels of homocysteine, slow down atherosclerosis, help prevent death from heart disease, and perhaps also treat hypertension.236,150,156,167 Fish oil has also become recognized as an effective treatment for early stages of rheumatoid arthritis. It appears to significantly reduce symptoms without side effects and may magnify the benefits of standard arthritis drugs.37,38 However, we have no evidence that fish oil slows the progress of the disease. Consult your rheumatologist to determine what treatment is best for you. Various essential fatty acids, including fish oil, flaxseed oil, and GLA (gamma-linolenic acid), are widely recommended for dysmenorrhea (menstrual pain), and two studies suggest that fish oil may indeed be effective.39,40 According to one small study, high doses of fish oil may produce benefits in bipolar disorder (more commonly known as manic-depressive illness), reducing risk of relapse and improving emotional state.41 It might also offer benefits in depression.154,168 Small studies also suggest that fish oil may be helpful in Raynaud's phenomenon (a condition in which a person's hands and feet show abnormal sensitivity to cold temperatures),42,43 sickle-cell anemia,45 and a form of kidney disease called IgA nephropathy.47 EPA and the related substance ethyl-EPA have been studied as supportive treatments for schizophrenia, but the results are incomplete and somewhat conflicting.48,148,169,170 One small study weakly suggests benefit in general for the autoimmune disease lupus;137 two other small studies failed to find it effective for kidney disease resulting from lupus.138,139 Evidence is mixed on whether fish oil can help prevent flare-ups of Crohn's disease, a condition in which parts of the digestive tract are highly inflamed. Interesting, but highly preliminary, evidence suggests that fish oil, or its constituents, might be helpful for preventing premature birth, improving vision in premature babies, treating kidney stones, alleviating the symptoms of chronic fatigue syndrome, and reducing the risk of prostate cancer.5359 Other highly preliminary evidence hints that DHA might enhance the effects of the cancer chemotherapy drug doxorubicin,157 and decrease side effects of another such medication, irinotecan.158 NOTE: If you are on cancer chemotherapy, do not use DHA (or any other supplement) except under the supervision of a physician. Fish oil has also been proposed as a treatment for many other conditions, including diabetic neuropathy,60allergies, and gout, but there has been little real scientific investigation of these uses. Small double-blind trials suggest that fish oil might be helpful for reducing symptoms of ulcerative colitis.6165 However, another small double-blind placebo-controlled trial failed to find benefit.66 In addtion, regular use of fish oil has not been found effective for preventing disease flare-ups,67,68 or (in combination with GLA) for maintaining remission.159 Despite widely publicized claims that fish oil helps asthma, most preliminary studies have failed to provide evidence that it is effective, and one study found that fish oil can actually worsen aspirin-related asthma.6977,171 A 16-week, double-blind, placebo-controlled study of 167 individuals with recurrent migraine headaches found that fish oil did not significantly reduce headache frequency or severity.149 Conflicting results have been seen in other, much smaller trials.172,173 Fish oil is also sometimes recommended for enhancing immunity in HIV infection. However, one 6-month double-blind study found that a combination of the omega-3 fatty acids in fish oil plus the amino acid arginine was no more effective than placebo in improving immune function in people with HIV.78 Fish oil, however, might help individuals with HIV gain weight.79 Preliminary studies suggest fish oil may help symptoms of multiple sclerosis; however, one double-blind study found no difference between people taking fish oil and those taking olive oil (used as a placebo).8084 Although one study found fish oil somewhat helpful in psoriasis,133 a much larger study found no benefit.134 DHA has been evaluated as a possible treatment for male infertility, but a double-blind trial of 28 men with impaired sperm activity found no benefit.85 Some, but not all, studies suggest that fish oil and GLA taken along with calcium may be helpful in preventing osteoporosis.86,87 Fish oil and related fatty acids have been tried for ADHD, but there is little evidence that they are helpful.88,89 One promising, but highly preliminary, double-blind, placebo-controlled study suggests that combination therapy with fish oil and GLA may improve symptoms of the severe neurological illness called Huntingtons disease.155 -------------------------------------------------------------------------------- What Is the Scientific Evidence for Fish Oil? Heart Disease Prevention Studies on fish or fish oil for preventing cardiovascular disease, slowing the progression of cardiovascular disease, and preventing heart-related death have returned somewhat contradictory results.106-125,150,156 However, a review (technically a meta-analysis) of many studies on the subject suggests that when all the evidence is put together, it appears that fish or fish oil can reduce overall mortality, heart disease mortality, and sudden cardiac death (e.g., fatal arrythmia).152 Fish oil is believed to exert its primary benefit in cardiovascular disease by reducing serum triglycerides, although not all studies have found this effect.9093,151 DHA and EPA may have different effects on triglycerides, but again study results are not consistent; some studies found EPA more effective, while others did not.160-165 Like cholesterol, triglycerides are a type of fat in the blood that tends to damage the arteries, leading to heart disease. Reducing triglyceride levels should help prevent heart disease to some extent. However, the standard drug gemfibrozil appears to be more effective than fish oil for this purpose.94 Fish oil has been specifically studied for reducing triglyceride levels in people with diabetes, and it appears to do so safely and effectively.95 Similarly, some, but not all studies also suggest that fish, fish oil, or EPA or DHA separately can modestly raise the levels of HDL ("good") cholesterol.96,97,151,164,165 Additionally, fish oil may help the heart by "thinning" the blood and by reducing blood levels of homocysteine.98 Blood clots play a major role in heart attacks, and homocysteine is an amino acid that appears to raise the risk of heart disease. One study directly indicates that fish oil may be able to prevent blood clots from blocking the synthetic grafts inserted in people undergoing kidney dialysis.153 Studies contradict one another on whether fish oil can lower blood pressure,99104 but on balance it does seem to exert a modest positive effect.174 A 6-week, double-blind, placebo-controlled study of 59 overweight men suggests that the DHA in fish oil, but not the EPA, is responsible for this benefit.105 Rheumatoid Arthritis The omega-3 fatty acids in fish oil can help reduce the symptoms of rheumatoid arthritis, according to 13 double-blind placebo-controlled studies involving a total of over 500 people.126,127 This evidence is so strong that it has impressed many conventional physicians. However, unlike some conventional treatments, fish oil probably does not slow the progression of rheumatoid arthritis. Menstrual Pain Regular use of fish oil may reduce the pain of menstrual cramps. In a 4-month study of 42 young women aged 15 to 18, half the participants received a daily dose of 6 g of fish oil, providing 1,080 mg of EPA and 720 mg of DHA daily.128 After 2 months, they were switched to placebo for another 2 months. The other group received the same treatments in reverse order. The results showed that these young women experienced significantly less menstrual pain while they were taking fish oil. Another double-blind study followed 78 women, who received either fish oil, seal oil, fish oil with vitamin B12 (7.5 mcg daily), or placebo for three full menstrual periods.129 Significant improvements were seen in all treatment groups, but the fish oil plus B12 proved most effective, and its benefits continued for the longest time after treatment was stopped (3 months). The researchers offered no explanation why B12 should be helpful. Bipolar Disorder A 4-month double-blind placebo-controlled study of 30 individuals suggests that fish oil can produce benefits in bipolar disorder, reducing risk of relapse and improving emotional state.130 Eleven of the 14 individuals who took fish oil improved or remained well during the course of the study, while only 6 out of the 16 given placebo responded similarly. The study will now be repeated by Baylor University and Harvard Medical School/McLean Hospital, enrolling 120 people for a period of 3 years. Depression A 4-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in 20 individuals with depression.154 All but one participant were also taking standard antidepressants and had been taking them for at least three months. By week three, the level of depression had improved to a significantly greater extent in the fish oil group than in placebo group. Six of 10 participants given fish oil, but only one of 10 given placebo, showed at least a 50% reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a cure.) A double-blind, placebo-controlled study of 70 people who were still depressed despite standard therapy found that additional treatment with ethyl-EPA (a modified form of EPA) improved symptoms.175 Raynaud's Phenomenon In small, double-blind studies, fish oil has been found to reduce the severe finger and toe responses to cold temperatures that occur in Raynaud's phenomenon.131,132 However, these studies suggest that a higher than usual dosage must be used to get results, perhaps 12 g daily. Osteoporosis There is some evidence that essential fatty acids may enhance the effectiveness of calcium in osteoporosis. In one study, 65 postmenopausal women were given calcium along with either placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil) for a period of 18 months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group.135 However, a 12-month, double-blind trial of 42 postmenopausal women found no benefit.136 The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and already received enough essential fatty acids in their diet. Lupus Lupus is a serious autoimmune disease that can cause numerous problems, including fatigue, joint pain, and kidney disease. One small, 34-week, double-blind, placebo-controlled crossover study compared placebo against daily doses of EPA (20 g) from fish oil.137 A total of 17 individuals completed the trial. Of these, 14 showed improvement when taking EPA, while only 4 did so when treated with placebo. Other small studies failed to find fish oil helpful for lupus nephritis (kidney damage caused by lupus).138,139 Attention Deficit and Hyperactivity Disorder (ADHD) Based on evidence that essential fatty acids are necessary for the proper development of brain function in growing children, EFAs have been tried for the treatment of ADHD and related conditions. A preliminary double-blind placebo-controlled trial found some evidence that a supplement containing fish oil and evening primrose oil might improve ADHD symptoms.140 However, a high dropout rate makes the results of this trial somewhat unreliable. In a double-blind placebo-controlled trial of children already using stimulant therapy, addition of DHA for 4 months failed to further improve symptoms.141 -------------------------------------------------------------------------------- Safety Issues Fish oil appears to be safe. The most common problem is fishy burps. However, concerns have been raised that some fish oil products contain excessive levels of toxic substances such as organochlorines and PCBs.166 If possible, try to purchase fish oil products certified not to contain significant levels of these contaminants. Because fish oil has a mild "blood-thinning" effect, it should not be combined with powerful blood-thinning medications, such as Coumadin (warfarin) or heparin, except on a physician's advice. However, contrary to some reports, fish oil does not seem to cause bleeding problems when it is taken by itself,142 or even with aspirin.143 Also, fish oil does not appear to raise blood sugar levels in people with diabetes.144,145 Nonetheless, if you have diabetes, you should not take any supplement except on the advice of a physician. Fish oil may temporarily raise the level of LDL ("bad") cholesterol, but this effect seems to be short-lived, and levels return to normal with continued use.146,147 If you decide to use cod liver oil as your fish oil supplement, make sure you do not exceed the safe maximum intake of vitamin A and vitamin D. These vitamins are fat soluble, which means that excess amounts tend to build up in your body, possibly reaching toxic levels. The official maximum daily intake of vitamin A is 3,000 mcg for pregnant women as well as other adults. Look at the bottle label to determine how much vitamin A you are receiving. (It is less likely that you will get enough vitamin D to produce toxic effects.) -------------------------------------------------------------------------------- Interactions You Should Know About If you are taking Coumadin (warfarin)or heparin, do not take fish oil except on the advice of a physician. -------------------------------------------------------------------------------- References 1. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645S1654. 2. Shekelle RB, Shryock AM, Paul O, et al. Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. N Engl J Med. 1981;304:6570. 3. Kromhout D, Bosschieter EB, De Lezenne Coulander C. The inverse relation between fish consumption and 20- year mortality from coronary heart disease. N Engl J Med. 1985;312:12051209. 4. Harris WS. N-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 suppl):S1645S1654. 5. 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