Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
A new Cochrane systematic review, published today in the Cochrane Library, combines the results of seventy-nine randomised trials involving 112,059 people. These studies assessed effects of consuming additional omega 3 fat, compared to usual or lower omega 3, on diseases of the heart and circulation. Twenty-five studies were assessed as highly trustworthy because they were well designed and conducted.
The chemical structures of EPA and DHA are very similar and they compete for uptake and processing resources. During digestion, the triglyceride molecules in standard fish oil are broken down into a mono glycerol and two free fatty acids, small enough to be absorbed into cells of the gut lining. More often than not, DHA is the fatty acid that remains attached to the glycerol backbone, meaning in essence that DHA gets a ‘free pass’ into the gut, while the remaining free fatty acids (more often EPA) must reattach onto a glycerol molecule or risk being oxidised and used as fuel. The implication of this is that DHA levels in our cells are often concentrated at the expense of EPA after absorption when taking EPA and DHA in the standard ratio of 1.5 to 1.

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.

Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.

Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.
ADD ADHD Ageing Allergies Alzheimer's Arthritis Autism baby Behaviour Brain function Cancer CFS Chronic Fatigue Concentration Dementia Depression Diabetes Digestion Dyslexia Dyspraxia Energy EPA Fertility Fibromyalgia General Health Good fats Healthy omega-3 Heart health Hormones IBS Immune System Inflammation Joints M.E. Mental health Mood Omega-3 Pregnancy Psoriasis Skin Sleep Stress Vegetarian nutrients Vegetarian Omega-3 Weight management
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.
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Full citation: Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub3.
The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
3. DHA affects your child's learning and behavior. Do you want to maximize your child's intellectual potential? A study published in Plos One in June 20138 linked low levels of DHA with poorer reading, and memory and behavioral problems in healthy school-age children. In another study published in the American Journal of Clinical Nutrition in August 2013,9 children who consumed an omega-3 fat supplement as infants scored higher on rule learning, vocabulary, and intelligent testing at ages 3 to 5.
The way that fish oil does that is to interfere with carbohydrate metabolism, and in insulin-resistant people or in people with specific genetic differences that might predispose them to having very high triglycerides, you do benefit from interfering that pathway with the fish oil, but I would actually try a low-carbohydrate diet in a lot of those situations to see if that helps with lowering triglycerides, or in the case of insulin resistance, I would try to address the insulin resistance at its root cause.

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
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.
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.

Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
As you likely know (and as I’ve been discussing for years), omega-3 fatty acids have anti-inflammatory properties. They have been studied for the treatment and prevention of many diseases, several of which are related to inflammation, including heart disease, stroke, cancer, and Alzheimer’s disease. They have also been shown to be extraordinarily helpful in preventing and treating other brain conditions such as depression and other psychiatric disorders, attention deficit/hyperactivity disorder (ADHD), and concussions.
The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3

The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
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]
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.
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.
The National Institutes of Health (NIH) has created a website, NIH Clinical Research Trials and You, to help people learn about clinical trials, why they matter, and how to participate. The site includes questions and answers about clinical trials, guidance on how to find clinical trials through ClinicalTrials.gov and other resources, and stories about the personal experiences of clinical trial participants. Clinical trials are necessary to find better ways to prevent, diagnose, and treat diseases.
First, all Omega-3 products are not alike. Here's what I learned about Omega-3 from my research. The "3" relates to three sources of Omega-3 fatty acids. Two of them, DHA and EPA are found in marine products such as fish and krill. The third source, ALA, is from plants. So with fish oil you are getting two of the three sources at once. That makes sense to me as a good reason to take Omega-3 fish oil. You will also note below that many of the reasons we choose to take Omega-3 do not occur with plant-based products.

Most people get far too little omega-3s in their diet. In fact, research consistently indicates that the majority of Americans have just slightly more than half the amount of EPA and DHA in their tissues than they need for optimum brain and body health. This is partly due to a high dietary intake of unhealthy fats combined with an inadequate intake of EPA and DHA.
^ 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.
Another recent study shows that fatty fish consumption can cut the risk of eye-diabetes complications. The researches tracked the seafood consumption of about 3,600 diabetic men and women between the ages of 55 and 80 for nearly five years. The researchers found that people who regularly consumed 500 milligrams each day of omega-3 fatty acid in their diets (equal to two servings of fatty fish per week) were 48 percent less likely to develop diabetic retinopathy than those who consumed less. (23)
In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24
Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di, Gregorio D., Di, Mascio R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P., Mantini, L., Marfisi, R. M., Mastrogiuseppe, G., Mininni, N., Nicolosi, G. L., Santini, M., Schweiger, C., Tavazzi, L., Tognoni, G., Tucci, C., and Valagussa, F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 4-23-2002;105(16):1897-1903. View abstract.
36. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002;105:1897–903. [PubMed]
Findings  In this systematic review and meta-analysis of 19 clinical trials including 2240 participants from 11 countries, improvement in anxiety symptoms was associated with omega-3 polyunsaturated fatty acid treatment compared with controls in both placebo-controlled and non–placebo-controlled trials. The anxiolytic effects of omega-3 polyunsaturated fatty acids were also stronger in participants with clinical conditions than in subclinical populations.
ACS Breast Cancer Screening Guideline CDC Guideline for Prescribing Opioids CDC Guideline for Prevention of Surgical Site Infections Consensus Definitions for Sepsis and Septic Shock Global Burden of Cancer, 1990-2016 Global Burden of Disease in Children, 1990-2013 Global Burden of Hypertension, 1990-2015 Global Firearm Mortality, 1990-2016 Health Care Spending in the US and Other High-Income Countries Income and Life Expectancy in the US JNC 8 Guideline for Management of High Blood Pressure President Obama on US Health Care Reform Screening for Colorectal Cancer Screening for Depression in Adults Screening for Prostate Cancer Statins for Primary Prevention of Cardiovascular Disease The State of US Health, 1990-2016 US Burden of Cardiovascular Disease, 1990-2016 WMA Declaration of Helsinki, 7th Revision

DHA is one of the most prevalent fatty acids in the brain. This could partly explain why our brains do better with a greater supply. A Rush Institute for Healthy Aging study analyzed fish-eating patterns of more than 800 men and women, ages 65 to 94. Those eating fish at least once a week were much less likely to develop Alzheimer's disease than those who turned up their nose at it.

Dangour, A. D., Allen, E., Elbourne, D., Fasey, N., Fletcher, A. E., Hardy, P., Holder, G. E., Knight, R., Letley, L., Richards, M., and Uauy, R. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am.J.Clin.Nutr. 2010;91(6):1725-1732. View abstract.
Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.
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.
Hamazaki, K., Syafruddin, D., Tunru, I. S., Azwir, M. F., Asih, P. B., Sawazaki, S., and Hamazaki, T. The effects of docosahexaenoic acid-rich fish oil on behavior, school attendance rate and malaria infection in school children--a double-blind, randomized, placebo-controlled trial in Lampung, Indonesia. Asia Pac.J Clin Nutr 2008;17(2):258-263. View abstract.
Dyerberg, J., Eskesen, D. C., Andersen, P. W., Astrup, A., Buemann, B., Christensen, J. H., Clausen, P., Rasmussen, B. F., Schmidt, E. B., Tholstrup, T., Toft, E., Toubro, S., and Stender, S. Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study. Eur.J.Clin.Nutr. 2004;58(7):1062-1070. View abstract.
Sorgi, P. J., Hallowell, E. M., Hutchins, H. L. & Sears, B. (2007, January 17). Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder. Nutrition Journal 6(16). Retrieved from http://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-16
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.
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
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).
I have been a long time user of Fish Oils for their anti-inflammatory action, unfortunately I have not really obtained much benefit in that area, though the benefits of eye health have been very good. I have been thinking of dropping this supplement for a number of reasons, first, I read a while back the possibility of “sudden death” in those that supplement in larger quantities, I use 1-2 tablespoons since I have an autoimmune issue. Now that you have brought forth the information that Fish Oil suppresses CD8+ counts I will definitely do so, reason being CD8+ T cells are very much at the forefront of containing the Epstein Barr virus and this virus has been implicated in most autoimmune issues. I doubt it will make a difference with my AI, but perhaps it will help prevent other issues down the line. Keep up the great work, very informative!
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.
While fish for dinner is one way to get EPA and DHA, most people don’t eat the suggested two to three servings of oily fish per week to reap the benefits of omega-3s. What’s more, there are extremely few food sources, aside from fish, that naturally provide EPA and DHA. With all the benefits that can come from fish oil, it’s no surprise that these supplements are increasing in popularity.

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.