Healthy cells require a delicate balance of EPA and DHA and the body employs clever mechanisms to support this natural equilibrium. DHA levels are self-regulated through inhibiting the activity of the enzyme delta-6 desaturase – the very enzyme that supports the conversion of EPA into DHA – to ensure levels of DHA do not become too high. It is therefore possible to have too much preformed DHA, if our supplement intake exceeds the body’s needs.
A tremendous body of research has been conducted on these important nutrients since it was first discovered in the 1950s that fish oil offered many health benefits and that these benefits were attributable to a type of polyunsaturated fat called omega-3. Despite the volumes of research on omega-3s, it is only in recent years (within the last 15 years or so) that the actions of EPA and DHA have come to be understood individually. Researchers now often investigate the actions of EPA and DHA individually rather than together, no longer simply under the generic label omega-3 as they are widely referred to.
There are numerous omega-3 sources with varying proportions of EPA and DHA, and the balance of EPA and DHA in a supplement influences the actions of these fats in the body. For more information about the different types of omega-3 sources and which are most suited for your individual needs, read our page on the different types of omega-3 supplements
for canned sardines i noticed the omega 3 EPA/DHA levels (written on the can) varied between the different company brands (sometimes by a lot!) , and also, the EPA/DHA amounts varied depending on what was added in the can with the sardines (sunflower oil, olive oil, brine, spring water, etc --- little note: there's more fat in the oily fish, than found in the brine/spring water)
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.
“Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine.” We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.
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.
The results of several small studies had suggested that taking omega-3 supplements might help relieve symptoms of dry eye disease. However, a 2018 NIH-sponsored study that tested omega-3 supplements for a full year in a larger group (535 study participants) with moderate-to-severe dry eye disease found that the supplements were no more helpful than a placebo (an inactive substance).
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.
They also found that taking more long-chain omega 3 fats (including EPA and DHA), primarily through supplements probably makes little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities. Long-chain omega 3 fats probably did reduce some blood fats, triglycerides and HDL cholesterol. Reducing triglycerides is likely to be protective of heart diseases, but reducing HDL has the opposite effect. The researchers collected information on harms from the studies, but information on bleeding and blood clots was very limited. 
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).
The American Heart Association (AHA) recommends that everyone eats fish (particularly fatty, coldwater fish) at least twice a week. Salmon, mackerel, herring, sardines, lake trout, and tuna are especially high in omega-3 fatty acids. While foods are your best bet for getting omega-3s in your diet, fish oil supplements are also available for those who do not like fish. The heart-healthy benefits of regular doses of fish oil supplements are unclear, so talk to your doctor to see if they're right for you. If you have heart disease or high triglyceride levels, you may need even more omega-3 fatty acids. Ask your doctor if you should take higher doses of fish oil supplements to get the omega-3s you need.
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.
The omega-3 index is also important because it is inversely related to one’s omega-6 to omega-3 ratio — another important measurement (3). A lower omega-6/omega-3 ratio (meaning, you consume a balanced amount of these two fatty acid families) is associated with a reduced risk of many chronic diseases, including cardiovascular disease, cancer, and autoimmune disease, to name a few (4). Of course, most people get far too much omega-6 and too little omega-3, thanks to the plethora of highly processed foods in the Western diet.

Some people who are hypersensitive to fish or have a known allergy to fish products may have a negative reaction to fatty acids which were derived from fish. Some fish oil tablets are also produced with alpha-linolenic acids which come from nuts, which may aggravate those which have an allergy to these products. In many cases these allergies will manifest themselves as a skin rash, but the symptoms could be more severe depending on the severity of your allergies. People with this concern will need to avoid using these products.
Thanks for the informative article. You mentioned that those taking high doses of DHA should supplement it with trace amounts of GLA. What GLA source would you recommend, and how much per day? I will be taking around 3400 mg of epa and 2200 mg DHA per day. I've heard that Borage Oil is more potent in GLA than evening primrose, but that it can lead to increased clotting and increased risk of heart attack, stroke, etc due to increased thromboxane B2. The main reason I want to stay away from the primrose is because it is extremely rich in linoleic acid. Thanks.
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.
This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.

Because of the preliminary state of knowledge on the effects of omega-3 PUFA treatment on anxiety, we decided to include as many studies as possible and not to set further limitations on specific characteristics, such as length of study, diagnosis, omega-3 PUFA dosage, omega-3 PUFA preparation (EPA to DHA ratio), rated anxiety coding scale, or type of control. Therefore, we chose to make the inclusion criteria as broad as possible to avoid missing any potentially eligible studies. The inclusion criteria included clinical trials in humans (randomized or nonrandomized), studies investigating the effects of omega-3 PUFA treatment on anxiety symptoms, and formal published articles in peer-reviewed journals. The clinical trials could be placebo controlled or non–placebo controlled. The target participants could include healthy volunteers, patients with psychiatric illness, and patients with physical illnesses other than psychiatric illnesses. The exclusion criteria included case reports or series, animal studies or review articles, and studies not investigating the effects of omega-3 PUFA treatment on anxiety symptoms. We did not set any language limitation to increase the number of eligible articles. Figure 1 shows the literature search and screening protocol.

When it comes to omega-3 benefits, there are rarely nutrients that pack this many positive health outcomes into one compound. The most commonly known benefit of omega-3s is a reduced risk of heart disease, but that’s not the only studied plus of getting lots of omega-3s in your diet — from fetal development to retinal function to weight management (and a lot more in between), these acids support and promote optimal health for anyone. (1)
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.
Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.
Sekikawa, A., Curb, D., Ueshima, H., El-Saed, A., Kadowaki, T., Abbott, R. D., ... Kuller, L. H. (2008 August 5). Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese Americans, and Whites: a cross-sectional study. Journal of the American College of Cardiology 52(6), 417–424. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736602/

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]
High triglycerides. Most research shows that fish oil from supplements and food sources can reduce triglyceride levels. The effects of fish oil appear to be the greatest in people who have very high triglyceride levels. Also the amount of fish oil consumed seems to directly affect how much triglyceride levels are reduced. Some fish oil supplements including Lovaza, Omtryg, and Epanova have been approved by the FDA to lower triglycerides.
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