Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Ness, A. R., Moore, H. J., Worthington, H. V., Durrington, P. N., Higgins, J. P., Capps, N. E., Riemersma, R. A., Ebrahim, S. B., and Davey, Smith G. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 4-1-2006;332(7544):752-760. View abstract.


The FDA product label on Lovaza warns of potential bleeding complications with the coadministration of anticoagulants. This warning is based on observational studies that suggested a prolonged bleeding time in populations ingesting high levels of fish oil77 and on in vitro studies that demonstrated an effect on pro-thrombotic mediators such as a reduction in thromboxane A2 production78 and platelet activation factor.79 The same trend, however, has not been clearly demonstrated in measurements of clotting times or in factors of fibrinolysis.80 In addition, in randomized clinical trials of patients undergoing coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, endarterectomy and diagnostic angiography, no adverse bleeding related events have been demonstrated.81 For example, in a trial of 500 patients randomized to pretreatment with 6.9 g of DHA and EPA preparation 2 weeks before balloon percutaneous transluminal coronary angioplasty (where all the patients received 325 mg/d of aspirin and heparin bolus periprocedure), no difference was seen in bleeding complications.82 Similar results were seen in a trial of 610 patients undergoing coronary artery bypass graft surgery, randomized to either placebo or 4 g/d of fish oil and then further randomized to aspirin or warfarin (dosed to an international normalized ratio [INR] goal of 2.5–4.2). At 1 year, the number of bleeding complications was not increased.15 The effect of fish oil on INR values has not been studied extensively, but a small, randomized trial showed that fish oil did not alter the Coumadin dosing regimen.83 There is very little evidence that a lower target INR is necessary in patients receiving chronic warfarin therapy and fish oil.
It is also believed that women who do not have a sufficient intake of EPA and DHA in their diet suffer from depression after childbirth, as there is a transfer of some amount of brain mass from the mother to the child in the last stages of pregnancy. Thus, it is very beneficial to consume fish oil either by eating fish or taking fish oil supplements, tablets, capsules, or pills during pregnancy for the overall development of the child and the well-being of the mother. However, it should be noted that fish oil obtained from the liver of the fish, example – cod liver oil, should not be consumed during pregnancy as cod liver oil is high in retinol and vitamin A, which are usually known to cause birth defects.
This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
The U.S. Food and Drug Administration recommends consuming no more than 3 g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements. Higher doses are sometimes used to lower triglycerides, but anyone taking omega-3s for this purpose should be under the care of a healthcare provider because these doses could cause bleeding problems and possibly affect immune function. Any side effects from taking omega-3 supplements in smaller amounts are usually mild. They include an unpleasant taste in the mouth, bad breath, heartburn, nausea, stomach discomfort, diarrhea, headache, and smelly sweat.

A scientific review published in 2013 looked at omega-3 polyunsaturated fatty acids and prostate cancer prevention. Researchers concluded that there’s a great deal of evidence suggesting that omega-3s have antiproliferative effects – which means they inhibit cancer cell growth – in cancer cell lines, animal models and humans. In addition, the “direct effects on cancer cells” and indirect anti-inflammatory effects on the immune system fighting the cancer likely contribute to the ability of omega-3 fatty acids to inhibit tumor growth. (14)


Carrero, J. J., Fonolla, J., Marti, J. L., Jimenez, J., Boza, J. J., and Lopez-Huertas, E. Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program. J.Nutr. 2007;137(2):384-390. View abstract.

The bottom line of all that is that there was no clear health benefit from consuming omega-3 fatty acids in food or supplements. There was a suggestion of a possible benefit from LCn3 on cardiac events, but this did not hold up when they took into consideration the quality of the evidence. The better trials, with less risk of bias, tended to be negative.

To date, no studies have assessed mortality or nonfatal MI in diabetic patients treated with fish oil.52–54 A recent comprehensive meta-analysis analyzed the effect of fish oil supplements on metabolic parameters when added to usual care in patients with type 2 diabetes mellitus or impaired glucose tolerance.54 The meta-analysis included a total of 23 small, randomized trials with over 1000 patients that were assessed for lipid and insulin resistance parameters. At a mean follow-up of approximately 9 weeks, triglyceride reduction was accomplished but no significant changes were seen in total cholesterol, high-density lipoprotein-cholesterol, HgA1c levels, fasting glucose levels, fasting insulin, or in body weight. The largest randomized trial to date assessed approximately 400 patients with impaired glucose tolerance or insulin-dependent diabetes mel-litus, and as reflected in the larger meta-analysis, found no effect of moderate to high doses of fish oil on diabetic parameters.55 There are insufficient randomized data to comment on the combination of fish oil and specific diabetes medications and related mortality and/or morbidity.


Bianconi, L., Calo, L., Mennuni, M., Santini, L., Morosetti, P., Azzolini, P., Barbato, G., Biscione, F., Romano, P., and Santini, M. n-3 polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study. Europace. 2011;13(2):174-181. View abstract.
To exclude the possible confounding effects of clinical variables on the Hedges g, metaregression analysis was conducted with an unrestricted maximum likelihood random-effects model of single variables when there were more than 10 data sets available. Specifically, the clinical variables of interest included mean age, female proportion, sample size, mean body mass index, daily omega-3 PUFA dosage, EPA to DHA ratio, treatment duration, dropout rate, and others. In addition, a subgroup meta-analysis was conducted to investigate potential sources of heterogeneity, specifically, a further subgroup meta-analysis focused on those trials that were placebo controlled or non–placebo controlled. To more clearly uncover the differences in the meta-analysis results among the recruited studies, a further subgroup meta-analysis was performed according to the presence of a specific clinical diagnosis or no specific clinical condition, mean omega-3 PUFA daily dosage, and mean age. In addition, in a previous study, the EPA percentage (ie, ≥60%) in the PUFA regimens had different effects on depression treatment.9 Therefore, we also arranged the subgroup meta-analysis based on the EPA percentage. Furthermore, we arranged subgroup meta-analysis procedures only when there were at least 3 data sets included.45 To investigate the potentially different estimated effect sizes between subgroups, we performed an interaction test and calculated the corresponding P values.46
Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[15] The various species range from lean to fatty and their oil content in the tissues has been shown to vary from 0.7% to 15.5%.[16] They also differ in their effects on organ lipids.[15] Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish, and serum omega−3 fatty acid concentrations.[17] Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA.[17]
The randomized trials assessing the efficacy of fish oil supplementation on secondary prevention of CAD lend further evidence to the findings that fish oil may protect from sudden cardiac death.36 The Diet and Reinfarction Trial (DART),37 one of the first randomized trials of fish oil in CAD, has been interpreted as potential support for fish oil’s role in sudden death reduction because the primary outcome of all-cause mortality occurred within 2 months of the trial’s onset.38 After such a short time span, it was believed that atherosclerosis would not be altered and therefore another mechanism was reducing mortality. This was further supported by the fact that nonfatal MIs were not reduced. Although the actual modes of death other than CAD-related deaths were not documented, it has been postulated to be secondary to a reduction in sudden death.39 The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Prevenzione40 (GISSI-Prevenzione) trial, a larger randomized trial of fish oil in CAD, has also been interpreted as evidence for fish oil’s protection against sudden death. Sudden death, however, was not a primary end point. Rather, the reduction in fatal events was driven by a reduction in cardiovascular death, which included coronary death, cardiac death, and sudden death.
Nakamura, N., Hamazaki, T., Ohta, M., Okuda, K., Urakaze, M., Sawazaki, S., Yamazaki, K., Satoh, A., Temaru, R., Ishikura, Y., Takata, M., Kishida, M., and Kobayashi, M. 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(1):22-25. View abstract.
Research conducted at the Louisiana State University has shown that fatty acids are effective in treating Alzheimer’s disease. Since fish oil is one of the best sources of essential fatty acids, including EPA and DHA, it helps in the treatment of Alzheimer’s disease. More research conducted at the University of California in Los Angeles (UCLA) validates the usefulness of fish oil as a possible remedy for the disease. The Alzheimer’s Association recommends fish containing a higher content of omega-3 fatty acids to patients since it acts as a defense against Alzheimer’s disease and dementia.
Several studies suggest that people suffering symptoms of depression and/or anxiety see improvement after adding an omega-3 supplement to their routine, even in double-blinded, randomized, controlled trials. (29, 30, 31, 32, 33) At least one study comparing a common depression medication found omega-3 supplements to be just as effective in combating depression symptoms. (34)
Despite this one study, you should still consider eating fish and other seafood as a healthy strategy. If we could absolutely, positively say that the benefits of eating seafood comes entirely from omega-3 fats, then downing fish oil pills would be an alternative to eating fish. But it’s more than likely that you need the entire orchestra of fish fats, vitamins, minerals, and supporting molecules, rather than the lone notes of EPA and DHA.
In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.

Additional side effects of fish oil supplements which have been reported include headache, short-term memory loss, depression, somatic disorders, and increased risk of colon cancer, nasopharyngitis, worsening of asthma symptoms, hemolytic anemia, decreased physical activity, increased appetite, a general uncomfortable feeling or increased blood pressure. The percentage of users that develop these side effects is not known. If these side effects become severe it is recommended that you stop using fish oil supplements.
Weak bones (osteoporosis). Research suggests that taking fish oil alone or together with calcium and evening primrose oil slows the rate of bone loss and increases bone density at the thigh bone (femur) and spine in elderly people with osteoporosis. But taking fish oil does not slow bone loss in older people with osteoarthritis in the knee but without weak bones.
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