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]

In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
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It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it. 
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.
Fish oil is also commonly used to treat conditions such as Rheumatoid arthritis, high blood pressure, ADHD, menstrual pain, hardening of the arteries or kidney problems. These conditions can be improved by improving blood flow, which omega-3 fatty acids in the blood stream. There is also some evidence that fish oil may help with conditions such as chest pain, liver disease, migraine prevention, gum infections, breast pain, and muscle soreness due to exercise, skin rashes and stomach ulcers.

Haberka, M., Mizia-Stec, K., Mizia, M., Janowska, J., Gieszczyk, K., Chmiel, A., Zahorska-Markiewicz, B., and Gasior, Z. N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction. Clin.Nutr. 2011;30(1):79-85. View abstract.
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)
For rheumatoid arthritis, one systematic review found consistent, but modest, evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs.[35] The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels. The National Center for Complementary and Integrative Health has concluded that "[n]o dietary supplement has shown clear benefits for rheumatoid arthritis", but that there is preliminary evidence that fish oil may be beneficial, but needs further study.[36]
In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).
A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."[42]
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Additionally, total polychlorinated biphenyl (PCB) content was measured in every product. All product recorded PCB levels within the Food and Drug Administration’s (FDA) 2 PPM limit for the edible parts of fish/shellfish as well as the stricter standards enacted by California’s Proposition 65, which requires products containing greater than 0.09 PPM of PCB content to bear a cancer warning. The worst offender, Now Foods Ultra Omega-3 Fish Oil, recorded 0.04 PPM of PCB content.
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.
Guallar, E., Aro, A., Jimenez, F. J., Martin-Moreno, J. M., Salminen, I., van't Veer, P., Kardinaal, A. F., Gomez-Aracena, J., Martin, B. C., Kohlmeier, L., Kark, J. D., Mazaev, V. P., Ringstad, J., Guillen, J., Riemersma, R. A., Huttunen, J. K., Thamm, M., and Kok, F. J. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler.Thromb.Vasc.Biol 1999;19(4):1111-1118. View abstract.
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.

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)
Fish oil is very beneficial for pregnant women because the DHA present in it helps in the development of the eyes and brain of the baby. It also helps to avoid premature births, low birth weight, and miscarriages. Research conducted in Denmark, which involved 8,729 pregnant women, concluded that a diet with low amounts of fish resulted in a higher risk of premature or preterm babies.
In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. (5)
According to the Cardiovascular Research Institute in Maastricht in Netherlands, “Epidemiological studies show that replacing fat with carbohydrates may even be worse [than the Western-type high-fat diet] and that various polyunsaturated fatty acids (FA) have beneficial rather than detrimental effects on CVD (cardiovascular disease) outcome.” This includes fish-oil fatty acids with anti-inflammatory properties, which can help prevent and reverse a plethora of cardiovascular diseases. (19)
^ Jump up to: a b Aursand, Marit; Mozuraityte, Revilija; Hamre, Kristin; Knutsen, Helle; Maage, Amund; Arukwe, Augustine (2011). Description of the processes in the value chain and risk assessment of decomposition substances and oxidation products in fish oils (PDF). Norwegian Scientific Committee for Food Safety. ISBN 978-82-8259-035-8. Retrieved 19 October 2012.[page needed]
Finally, in order for AA to be converted into inflammatory products it must be released from phospholipids (part of the cell membrane) using the enzyme phospholipase A2 and then converted by the enzyme cyclooxygenase. EPA utilises both of these enzymes, so if EPA levels are increased in the diet, it attracts enzyme away from AA to EPA – again giving rise to anti-inflammatory products instead of inflammatory ones.
EPA is the precursor to DHA in the body and can be converted to DHA with the enzyme delta-6 desaturase, but this process is inefficient in many people (much like the inefficiency of short-chain omega-3s to long-chain). For those individuals taking pure EPA products as well as those taking our EPA-rich products, we still recommend eating oily fish at least once each week to provide a natural source of DHA. Fish provides a unique nutritional package, supplying the diet with important amino acids (the building blocks of proteins) and antioxidants, including vitamins and minerals needed to process fats, so eating fish will also support the natural enzyme-dependent EPA to DHA conversion.
Fearon, K. C., Von Meyenfeldt, M. F., Moses, A. G., Van Geenen, R., Roy, A., Gouma, D. J., Giacosa, A., Van Gossum, A., Bauer, J., Barber, M. D., Aaronson, N. K., Voss, A. C., and Tisdale, M. J. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003;52(10):1479-1486. View abstract.
Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.
Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
Fish oil has only a small benefit on the risk of premature birth.[43][44] A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[45] A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".[46]
The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.[79][80] Women have higher ALA-to-DHA conversion efficiency than men, which is presumed[81] to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.[82]
Special attention should also be given to the fact that most women have major deficiencies of omega-3. A 1991 study at the Mayo Clinic focused on 19 "normal" pregnant women consuming "normal diets," and it showed that all were deficient in omega-3 fats. Another study compared Inuit (Eskimo) women to Canadian women, and it revealed omega-3 deficiency in the milk of the Canadian nursing moms.
For those who do not eat seafood, another way exists for you to get a healthy dose of EPA and DHA each day. Fish oil supplements, which are rich in EPA and DHA, can be made from a variety of fish, with the most common ones being halibut, tuna, salmon, cod liver, mackerel and herring. On average, one 3.5 ounce serving of fatty fish contains about 1 gram of omega-3s, which can be obtained through fish oil supplements, according to MedlinePlus.
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.
*Swordfish contains high levels of mercury, as does shark, king mackerel, and tilefish (sometimes called golden bass or golden snapper). Women who are or may become pregnant, nursing mothers, and young children should avoid these high-mercury species of fish, but can eat up to 12 ounces (two average meals) a week of a variety of fish and shellfish that are lower in mercury.
Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16
An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)
In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29
Dioxins and PCBs may be carcinogenic at low levels of exposure over time. These substances are identified and measured in one of two categories, dioxin-like PCBs and total PCBs. While the U.S. FDA has not set a limit for PCBs in supplements, the Global Organization for EPA and DHA (GOED) has established a guideline allowing for no more than 3 picograms of dioxin-like PCBs per gram of fish oil. In 2012, samples from 35 fish oil supplements were tested for PCBs. Trace amounts of PCBs were found in all samples, and two samples exceeded the GOED‘s limit.[52] Although trace amounts of PCBs contribute to overall PCB exposure, Consumerlab.com claims the amounts reported by tests it ordered on fish oil supplements are far below those found in a single typical serving of fish.[52]
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. [PubMed]
6. Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jimenez M, Gil A, Rivero M, Veszpremi B, Decsi T, et al. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr. 2007;85:1392–400. [PubMed]
An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)
Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
ALA is an essential fatty acid, meaning that your body can’t make it, so you must get it from the foods and beverages you consume. Your body can convert some ALA into EPA and then to DHA, but only in very small amounts. Therefore, getting EPA and DHA from foods (and dietary supplements if you take them) is the only practical way to increase levels of these omega-3 fatty acids in your body.
Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms. In addition, participants receiving supplements containing less than 60% EPA showed a significant association, but not those receiving supplements containing 60% or more EPA. The depression literature supports the clinical benefits of EPA-enriched formulations (≥60% or ≥50%) compared with placebo for the treatment of clinical depression.9,13,73-75 This opposite effect of EPA-enriched formations on anxiety and depression is intriguing and possibly linked to a distinct underlying mechanism of omega-3 PUFAs. Exploration of the effects of omega-3 PUFAs on anxiety symptoms is just beginning and studies assessing the dose response anxiolytic effects of omega-3 PUFAs have not yet been performed. Further phase 2 trials of anxiety symptoms among participants with neuropsychiatric illness or physical illness should aim to determine the optimal dose.

Fish oil can be obtained from eating fish or by taking supplements. Fish that are especially rich in the beneficial oils known as omega-3 fatty acids include mackerel, herring, tuna, salmon, cod liver, whale blubber, and seal blubber. Two of the most important omega-3 fatty acids contained in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Make sure to see separate listings on EPA and DHA, as well as Cod Liver Oil, and Shark Liver Oil.
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