Secondary prevention fish oil studies demonstrate a significant reduction in MI. But unfortunately, both the observational and randomized trials were conducted in an era before the widespread use of HMG-CoA reductase inhibitors, and therefore, the incremental benefit is still unknown. Nevertheless, in patients receiving antiplatelet and anticoagulant therapy in addition to fish oil supplementation (even at doses as high as 4 g per day), no serious adverse complications have been reported.
Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.
The strongest evidence for a beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. (1) Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis. (1)
Respected health care organizations proposed intake recommendations for oily fish of two servings per week for healthy adults, which equates to approximately a daily total of 500 milligrams (mg) EPA and DHA.‡ The recommendation encourages adults already with or at-risk of developing cardiovascular disease to talk to their primary healthcare professional about supplementing with amounts greater than 500 mg of EPA and DHA per day. Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.
Humans are unable to place double bonds beyond position 9 on long chain polyunsaturated fatty acids (FA), making the omega-3 FA synthesized in plants and in marine microalgae essential elements to the human diet.1 Fish contain high levels of 2 omega-3 FA, eicosapentaenoic acid (EPA; C20:5 n-3), and docosahexaenoic acid [DHA]; C22:6 n-3)2,3 (Fig. 1). Many claims about the role of these omega-3 FA have been made in the prevention and treatment of cardiovascular disease. For instance, fish oil is seen as having a therapeutic role in coronary artery disease (CAD), heart failure, fatal and nonfatal arrhythmias, as well as offering an alternative or adjunct to the standard therapy for hypertriglyceridemia and diabetes. This review will highlight the potential mechanisms of fish oil on cardiovascular disease and provide an update of clinical trial results. The established uses in the treatment of hypertriglyceridemia and sources of omega-3 FA—both dietary and drug therapy—will be iterated, along with its potential application in combination with standard hypolipidemic agents. Finally, the limitations of current data will be addressed, as well as suggested recommendations for clinical use.

Nine studies with 10 data sets used omega-3 PUFA dosages of less than 2000 mg/d.35,47,48,51,53,55,56,60,61 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) (Figure 3B). Ten studies with 10 data sets used omega-3 PUFA dosages of at least 2000 mg/d.33,34,36,49,50,52,54,55,57-59 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02) (Figure 3B). Furthermore, there was no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .40).
Jump up ^ Kwak SM, Myung SK, Lee YJ, Seo HG (May 2012). "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials". Archives of Internal Medicine. 172 (9): 686–94. doi:10.1001/archinternmed.2012.262. PMID 22493407.
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)

In a 2009 letter on a pending revision to the Dietary Guidelines for Americans, the American Heart Association recommended 250–500 mg/day of EPA and DHA.[26] The Guidelines were revised again for 2015-2020; included is a recommendation that adults consume at least eight ounces of a variety of types of fish per week, equating to at least 250 mg/day of EPA + DHA.[citation needed] The Food and Drug Administration recommends not exceeding 3 grams per day of EPA + DHA from all sources, with no more than 2 grams per day from dietary supplements.[27]
Evidence in the population generally does not support a beneficial role for omega−3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death) or stroke.[4][19][20][21] A 2018 meta-analysis found no support that daily intake of one gram of omega-3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.[6] However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.[22] No protective effect against the development of stroke or all-cause mortality was seen in this population.[22] Eating a diet high in fish that contain long chain omega−3 fatty acids does appear to decrease the risk of stroke.[23] Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.[24] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[7]
Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis. 
Humans are unable to place double bonds beyond position 9 on long chain polyunsaturated fatty acids (FA), making the omega-3 FA synthesized in plants and in marine microalgae essential elements to the human diet.1 Fish contain high levels of 2 omega-3 FA, eicosapentaenoic acid (EPA; C20:5 n-3), and docosahexaenoic acid [DHA]; C22:6 n-3)2,3 (Fig. 1). Many claims about the role of these omega-3 FA have been made in the prevention and treatment of cardiovascular disease. For instance, fish oil is seen as having a therapeutic role in coronary artery disease (CAD), heart failure, fatal and nonfatal arrhythmias, as well as offering an alternative or adjunct to the standard therapy for hypertriglyceridemia and diabetes. This review will highlight the potential mechanisms of fish oil on cardiovascular disease and provide an update of clinical trial results. The established uses in the treatment of hypertriglyceridemia and sources of omega-3 FA—both dietary and drug therapy—will be iterated, along with its potential application in combination with standard hypolipidemic agents. Finally, the limitations of current data will be addressed, as well as suggested recommendations for clinical use.
Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.
Omega-3 fatty acids are found primarily in fish oil and certain marine algae. Because depression appears less common in nations where people eat large amounts of fish, scientists have investigated whether fish oils may prevent and/or treat depression and other mood disorders. Two omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — are thought to have the most potential to benefit people with mood disorders.
Bell, J. G., Miller, D., MacDonald, D. J., MacKinlay, E. E., Dick, J. R., Cheseldine, S., Boyle, R. M., Graham, C., and O'Hare, A. E. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr 2010;103(8):1160-1167. View abstract.
Rogers, P. J., Appleton, K. M., Kessler, D., Peters, T. J., Gunnell, D., Hayward, R. C., Heatherley, S. V., Christian, L. M., McNaughton, S. A., and Ness, A. R. 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(2):421-431. View abstract.
Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.
Those foods provide enormous amounts of other nutrients that are good for you. nSo it is way better to eat those foods than to take fish oil. With that said, some people find it very difficult to get vitamin A or vitamin D, and particularly for vitamin A, cod liver oil may be a very important source of that vitamin. Cod liver oil is a form of fish oil that happens to be high in the fat-soluble vitamins. Vitamin A is best found in liver. It’s better in my opinion to eat liver once a week, but there are a lot of people out there who are not going to eat liver once a week. So if you are using cod liver oil to get the vitamins that you can’t get from food—and I should point out that vitamin A can also be derived from plant foods, but many people genetically or for other reasons don’t derive it very well from plant foods.
Today the only Food and Drug Administration (FDA)-approved form of dietary omega-3 FA supplement is Lovaza (omega-3-acid ethyl esters; GlaxoSmithKline), which contains 375 mg of DHA and 465 mg of EPA per 1 g capsule. The myriad of dietary supplements of fish oil, including Kosher capsules, vary from comparable content to insignificant amounts, and for the most part can include other fats and cholesterols. In comparison, to achieve approximately 1 g of EPA and DHA in a meal, 12 ounces of canned light tuna, 2 to 3 ounces of sardines, 1.5 to 2.5 ounces of farmed Atlantic salmon, or 20 ounces of farmed catfish must be consumed (Table 1).65 Unfortunately, potentially high levels of harmful pollutants offset this source of omega-3 FA. The FDA action level for unacceptably high mercury content in fish is 1.0 μg/g. The mercury level in most fish is at or below 0.1 μg/g, but tilefish, swordfish, and king mackerel have high levels of mercury. The majority of fish species also contain <100 ng/g of polychlorinated biphenyls, which is below the FDA action level of 2000 ng/g. Dioxins, which do not have FDA action levels, are present in the majority of marine life.66
The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.

Interestingly, the results are also consistent with our recent findings that somatic anxiety is associated with omega-3 PUFA deficits and the genetic risks of PUFA metabolic enzyme cytosolic phospholipase A2 in major depressive disorder62,63 and interferon α–induced neuropsychiatric syndrome.63,64 Brain membranes contain a high proportion of omega-3 PUFAs and their derivatives and most animal and human studies suggest that a lack of omega-3 PUFAs in the brain might induce various behavioral and neuropsychiatric disorders,16,65-70 including anxiety-related behaviors.12,18,19,32,49,71 Emerging evidence suggests that omega-3 PUFAs interfere with and possibly control several neurobiological processes, such as neurotransmitter systems, neuroplasticity, and inflammation,12,72 which is postulated to be the mechanism underlying anxiety and depression.


During pregnancy and breastfeeding, eating 8 to 12 ounces per week of fish and other seafood may improve your baby’s health. However, it is important to choose fish that are higher in EPA and DHA and lower in mercury. Examples are salmon, herring, sardines, and trout. It is not clear whether taking dietary supplements containing EPA and DHA during pregnancy or breastfeeding affects a baby’s health or development. However, some studies show that taking these supplements may slightly increase a baby’s weight at birth and the length of time the baby is in the womb, both of which may be beneficial. Breast milk contains DHA. Most commercial infant formulas also contain DHA.
The omega-3 index may also be helpful for assessing health risks beyond cardiovascular disease. Studies are currently investigating the relationship between omega-3 index levels and mental health issues, like depression (15, 16, 17), cognitive functioning (18, 19), body weight (20), as well as eye health issues, like macular degeneration (21), to name just a few.
A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free".[66]
Weight loss. Some research shows that eating fish improves weight loss and decreases blood sugar in people who are overweight with high blood pressure. Early research also shows that taking a specific fish oil supplement (Hi-DHA, NuMega) lowers body fat when combined with exercise. But other evidence suggests that taking another specific fish oil supplement (Lovaza) does not lower body weight in overweight people.
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