Funding/Support: The work was supported in part by grant 17H04253, Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science; grant 30-A-17 from the National Cancer Center Research and Development Fund; grants MOST106-2314-B-039-027-MY, 106-2314-B-038-049, 106-2314-B-039-031, 106-2314-B-039-035, 104-2314-B-039-022-MY2, and 104-2314-B-039-050-MY3 from the Ministry of Science and Technology, Taiwan; grant HRI-EX105-10528NI from the National Health Research Institutes, Taiwan; and grants CRS-106-063, DMR-107-202, and DMR-107-204 from the China Medical University, Taiwan.
If you’ve been paying attention to health headlines over the last few decades, you’ve likely heard about essential fatty acids (EFAs) — specifically omega-3s and omega-6s. These nutrients play many vital roles in supporting our overall health, including increasing nutrient absorption, ensuring proper growth and development of the brain and nervous system, and reducing the risk of chronic illnesses, such as heart disease.  Click here for a guide to understanding omega-3 and omega-6 fatty acids and how they influence your health.
Gajos, G., Zalewski, J., Rostoff, P., Nessler, J., Piwowarska, W., & Undas, A. (2011, May 26). Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI Clot). Arteriosclerosis, Thrombosis, and Vascular Biology 111.228593. Retrieved from http://atvb.ahajournals.org/content/early/2011/05/26/ATVBAHA.111.228593.abstract

Infant development. There is some evidence that mothers who eat fish or take fish oil supplements during pregnancy may improve some aspects of their baby's mental development. Taking fish oil during breast-feeding does not have this effect. However, feeding infants formula fortified with fish oil appears to improve some aspect of the baby's vision by the age of 2 months.
An excessive dosage of fish oil can have adverse allergies and side effects on the body. Furthermore, fish oil can be problematic if you have certain conditions so it is necessary to consume fish oil supplements cautiously. Moreover, it can be consumed in various forms. These include eating the fish directly by baking, roasting, frying, grilling, broiling, or smoking it. It can also be consumed in the form of concentrated dietary supplements like liquid, tablet, capsule, pill, or soft gels. Also, there are various pharmaceutical grades of the oil. It is not necessary to constantly consume pharmaceutical-grade oil or even supplements. You should also consult your doctor to confirm the mode of consuming fish oil and the overall need for it in your diet.
The Federal Government’s Dietary Guidelines for Americans 2015–2020 recommends that adults eat 8 or more ounces of a variety of seafood (fish or shellfish) per week for the total package of nutrients seafood provides, and that some seafood choices with higher amounts of EPA and DHA be included. Smaller amounts of seafood are recommended for young children.
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.
Gerber, J. G., Kitch, D. W., Fichtenbaum, C. J., Zackin, R. A., Charles, S., Hogg, E., Acosta, E. P., Connick, E., Wohl, D., Kojic, E. M., Benson, C. A., and Aberg, J. A. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J.Acquir.Immune.Defic.Syndr. 4-1-2008;47(4):459-466. View abstract.
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
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.
Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
Increased EPA levels in the blood and cell membranes effectively regulates inflammatory pathways and reduces total inflammatory ‘load’, so for any inflammatory conditions or concerns, we recommend a phase of pure EPA supplementation for at least 3-6 months. Pre-loading the body with pure EPA (without the opposing actions of DHA for uptake and utilisation) ensures constant replenishment of EPA ’supplies’ to support its high rate of turnover. Since DHA levels remain fairly stable and much lower daily amounts are required, DHA levels can be supported continually through dietary intake, or increased to 250 mg daily in later stages of treatment through supplementation.
The various enzymes (COX and LOX) that make inflammatory eicosanoids can accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty in converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation whereas EPA can have a powerful impact.
Secondly, when we consume EPA, it inhibits the production of AA from DGLA and also competes with AA for uptake into cell membranes and can therefore lower the amount of AA in membranes by literally saturating the cell – in essence, it takes up more of the available ‘space’ and displaces AA. When there is less AA present, there is a reduced capacity for it to produce inflammatory products.
In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning, but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.[105] The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."[citation needed] As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids,[105] although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.[8]
Omega 3 fatty acids—found in supplements and naturally in some foods like certain fish, and nuts and seeds—have long been touted for their health benefits, especially heart health. Yet, a lot is still unknown, including whether it's better to get your omega 3 fats from pills or in food—and the debate continues regarding how much they may actually help you avoid heart disease.
Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.

I now suspect that those thousands of gel-covered capsules I’ve swallowed over the years may have done little more than enrich the pockets of supplement producers and sellers. A number of extensive analyses have been conducted, some supporting and others refuting the value of fish oils to the cardiovascular system, along with studies of other purported health benefits that also have had mixed results.
Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[60][61] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[62]
Bergmann, R. L., Haschke-Becher, E., Klassen-Wigger, P., Bergmann, K. E., Richter, R., Dudenhausen, J. W., Grathwohl, D., and Haschke, F. Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Ann Nutr Metab 2008;52(2):157-166. View abstract.
The 'essential' fatty acids were given their name when researchers found that they are essential to normal growth in young children and animals. The omega−3 fatty acid DHA, also known as docosahexaenoic acid, is found in high abundance in the human brain.[70] It is produced by a desaturation process, but humans lack the desaturase enzyme, which acts to insert double bonds at the ω6 and ω3 position.[70] Therefore, the ω6 and ω3 polyunsaturated fatty acids cannot be synthesized and are appropriately called essential fatty acids.[70]

Human growth and intellectual development – DHA plays a very important role during fetal development, early infancy and old age. High concentrations of DHA are found in the brain and increase 300 to 500 percent in an infant’s brain during the last trimester of pregnancy. Adding DHA to a pregnant mother’s diet may be beneficial for the fetus’s brain development. Elderly people should also take EPA DHA, because as we get older, our bodies form less EPA and DHA, which may cause less mental focus and cognitive function. Taking EPA DHA also may help with mental abnormalities, such as Alzheimer’s disease and dementia.
The Federal Government’s Dietary Guidelines for Americans 2015–2020 recommends that adults eat 8 or more ounces of a variety of seafood (fish or shellfish) per week for the total package of nutrients seafood provides, and that some seafood choices with higher amounts of EPA and DHA be included. Smaller amounts of seafood are recommended for young children.

Joensen, A. M., Schmidt, E. B., Dethlefsen, C., Johnsen, S. P., Tjonneland, A., Rasmussen, L. H., and Overvad, K. Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study. Br J Nutr 2010;103(4):602-607. View abstract.


Omega-3 fatty acids get a fair amount of time in the press and a great deal of respect at this point. But do you know what omega-3s are? What omega-3 benefits could convince you to add more oily fish (or maybe a supplement) to your diet? Are omega-3 foods really that big of a deal when it comes to eating a nutrient-dense diet? Could you be deficient in these fatty acids?

Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise, but this has not been supported by evidence in humans. (4) In the Health Professionals Follow-up Study, for example, the ratio of omega-6 to omega-3 fats wasn’t linked with risk of heart disease because both of these were beneficial. (5) Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats. Although there is no question that many Americans could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.
Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)
Fish oil supplements in our study averaged 473.3mg EPA + 243.1mg DHA in a single serving. These average values were stretched by outliers on both extremes of the spectrum. Nature Made Cod Liver Oil (50mg EPA/serving) and Schiff MegaRed Krill Oil (29mg DHA/serving) recorded category lows for the two omega-3 fatty acids. Ocean Blue Professional Omega-3 (1260mg EPA/serving) and Dr. Tobias Optimum Omega-3 Fish Oil (600mg DHA/serving), on the other hand, recorded category highs for EPA and DHA content.
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.

Henneicke-von Zepelin, H. H., Mrowietz, U., Farber, L., Bruck-Borchers, K., Schober, C., Huber, J., Lutz, G., Kohnen, R., Christophers, E., and Welzel, D. Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. Br J Dermatol 1993;129(6):713-717. View abstract.
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]
To reap all the omega-3 benefits, it may be difficult for some people to eat the required amounts of oily fish, particularly with the well-known dangers of farmed fish, which are more readily available to most Americans. That’s why some people consider a high-quality omega-3 supplement in addition to a well-rounded diet. I’ll discuss supplements in a moment, though.
The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).

A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)

Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
Mercury and polychlorinated biphenyls (PCBs) are common toxins in seafood. Although the U.S. banned the use of PCBs and DDT in 1976, these and other chemicals are still used in half the world's commercial chemical processes. Substances like these can hang around in the air, soil, and water for many years. They end up in the bodies of fish and animals.
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body,[1][2] and have other health benefits, such as treating hypertriglyceridemia, although claims of preventing heart attacks or strokes have not been supported.[3][4][5][6] Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression,[7][8] anxiety,[9][10][11] cancer, and macular degeneration, yet benefits in these conditions have not been verified.[12]
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)
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.

Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).
^ Jump up to: a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–34. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.
An analysis based on data from the Norwegian Women and Cancer Study (NOWAC) with regards to the dangers of persistent organic pollutants (POPs) in cod liver came to the conclusion that "in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found."[65]
If, however, we want to target the actions and benefits of either fat for more intensive support or clinical use, we need to alter the natural 1.5:1 EPA:DHA ratio found in most omega-3 sources such as fish oil – which is when concentrated supplements are especially useful. Certain forms of omega-3 called ethyl-ester and re-esterified triglyceride give nature a helping hand – allowing us to achieve targeted ratios of specific fatty acids at high concentration and physiologically active doses.
Omega-3 is a group of long-chain polyunsaturated fatty acids, perhaps most notably found in fatty fish. As science parses the biological actions of nutrients, it turns out that omega-3 fats do many good things for the body and the brain. Known as an "essential" fatty acid, meaning the body must take it in from food sources, omega-3 is important to human metabolism.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
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