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.
EPA and DHA are vital nutrients and may be taken to maintain healthy function of the following: brain and retina: DHA is a building block of tissue in the brain and retina of the eye. It helps with forming neural transmitters, such as phosphatidylserine, which is important for brain function. DHA is found in the retina of the eye and taking DHA may be necessary for maintaining healthy levels of DHA for normal eye function.
However, since the dosage of fish oil required for an ideal effect in the improvement of a patient is unknown, the Arthritis Center in the Department of Rheumatology at John Hopkins University considers including omega-3 fatty acids and fish oil in the treatment of arthritis as controversial. The University also cautions that arthritis patients must be wary of all the other side effects that can come from using fish oil. You can read more about arthritis on the web page of the Arthritis Foundation and the Arthritis Center.

The use of DHA by persons with epilepsy could decrease the frequency of their seizures. Studies have shown that children with epilepsy had a major improvement, i.e. decrease in the frequency of their seizures, but another study showed mixed results with 57 adults taking DHA supplementation. The 57 subjects demonstrated a decreased frequency of seizures for the first six weeks of the study, but for some, it was just a temporary improvement (R).
^ Jump up to: a b Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G (2006). "Risks and benefits of omega−3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ. 332 (7544): 752–60. doi:10.1136/bmj.38755.366331.2F. PMC 1420708. PMID 16565093. Retrieved 2006-07-07.[permanent dead link]

According to research conducted at Harvard University, omega-3 fatty acid deficiency is officially one of the top 10 causes of death in America, claiming the lives of up to 96,000 people each year. Out of the 12 dietary, lifestyle and metabolic risk factors examined in the study, omega-3 fatty acid deficiency ranked as the sixth highest killer of Americans. (1) These deaths are considered preventable since getting enough omega 3-fatty acids in your diet can ward off this now common cause of death, and fish oil benefits omega-3 intake as a potent omega-3 source.
This systematic review and meta-analysis of clinical trials conducted on participants with clinical anxiety symptoms provides the first meta-analytic evidence, to our knowledge, that omega-3 PUFA treatment may be associated with anxiety reduction, which might not only be due to a potential placebo effect, but also from some associations of treatment with reduced anxiety symptoms. The beneficial anxiolytic effects of omega-3 PUFAs might be stronger in participants with specific clinical diagnoses than in those without specific clinical conditions. Larger and well-designed clinical trials should be performed with high-dose omega-3 PUFAs, provided as monotherapy and as adjunctive treatment to standard therapy.
Abnormal rapid heart rhythms (ventricular arrhythmias). Population research suggests that eating a lot of fish has no effect on the risk for abnormal rapid heart rhythms. Clinical research is inconsistent. Some research shows that taking fish oil daily does not affect the risk for abnormal heart rhythms. But other research shows that taking fish oil for 11 months delays the development of the condition. However, overall, taking fish oil does not seem to reduce the risk of death in people with abnormal rapid heart rhythms.
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.
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.

Most U.S. adults fail to consume adequate amounts of foods rich in EPA and DHA on a regular basis (at least 8 ounces of fatty fish per week is recommended), and probably consume too many omega-6 fats in comparison (soybean oil, canola oil, cottonseed oil, etc.). This omega-3:omega-6 imbalance can have a negative effect on inflammation patterns and may also be implicated as a contributing factor to other processes related to cellular metabolism, hormone signaling, and even weight regulation.
For those who can’t or choose not to eat fatty fish, or who have certain health issues, supplementation is a way to increase omega-3 levels. “There are some conditions that might respond well to supplementation, such as depression or cardiovascular risk factors, including elevated triglycerides,” explains Kathie Madonna Swift, MS, RDN, LDN.  If you're ooking to increase your omega-3 levels, Click here for six tips to finding the right supplement.
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.
Subgroup meta-analysis of the anxiolytic effects of omega-3 polyunsaturated fatty acids (PUFAs) based on different EPA percentages. The anxiolytic effects of omega-3 PUFAs were significant in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g = 0.485; 95% CI, 0.017 to 0.954; P = .04) but not significant in the subgroups with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35).
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.
All people need to consume omega-3 fats regularly. The recommended daily intake for adults is 1.6 grams for males  and 1.1 grams for females, according to the National Institutes of Health. The omega-3 family encompasses numerous fatty acids, but three primary forms are eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. The first two forms primarily occur in fish, such as salmon, mackerel, and tuna. The third can be found in plant oils, including flaxseed, soybean, walnut, and canola oils.

There’s evidence that points to the mechanism behind the effects of fish oil on body composition, showing that fat burning at rest is increased with 6 grams/day of fish oil supplementation, and additional research suggests that higher omega-3 levels may be helpful for enhancing satiety during weight loss efforts. Other evidence suggests that fat loss may be a side-effect of the reduction in inflammation that fish oil can help with. Any way you look at it, supporting your dietary habits with 4 or more grams of fish oil per day is probably a good idea!
4. Omega-3 has been found to save the lives of children going through short bowel syndrome (SBS), which is uncommon but impacts thousands of people in the United States. SBS can occur from birth (when a portion of the intestine fails to develop) or due to an infectious inflammatory disease striking premature newborns. In adults, it can be caused by surgery for Crohn's disease or injury.
From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
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We’ve already seen that fish oil can help with depression-like symptoms in rats, but what about people? A study published in the journal Nutritional Neuroscience evaluated the effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder. Researchers found that there was a 40 percent decrease in major depression disorder symptoms in addition to marked improvements in amino acid and nutrition content in the brain, specifically, the right dorsolateral prefrontal cortex. (21)
Grigg, L. E., Kay, T. W., Valentine, P. A., Larkins, R., Flower, D. J., Manolas, E. G., O'Dea, K., Sinclair, A. J., Hopper, J. L., and Hunt, D. Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty. J Am Coll Cardiol. 3-1-1989;13(3):665-672. View abstract.
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)
In addition, there was no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.

Chemical structure of alpha-linolenic acid (ALA), an essential omega−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15). Although chemists count from the carbonyl carbon (blue numbering), biologists count from the n (ω) carbon (red numbering). Note that, from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n-3". This is explained by the fact that the n end is almost never changed during physiological transformations in the human body, as it is more energy-stable, and other compounds can be synthesized from the other carbonyl end, for example in glycerides, or from double bonds in the middle of the chain.


We are now fortunate to understand how these fats work in combination and in isolation, how they are digested, absorbed and utilised in the body, so we are able to tailor different blends of EPA and DHA according to the health benefits we are seeking to achieve. At Igennus, we have long specialised in the role of the omega-3 fatty acid EPA in clinical nutrition, as a powerful tool in the patient’s ‘toolkit’ for helping to regulate inflammation by restoring several biological markers, known as the omega-6 to omega-3 ratio and AA to EPA ratio. Before we discuss the therapeutic role of EPA in nutritional medicine, here’s a very brief summary of the role of both EPA and DHA in health throughout life.
Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.
The biggest cause of omega-3 deficiency is the overconsumption of foods high in omega-6 fatty acids. Omega-6 comes from things like fried foods, fast foods and boxed foods that contain vegetables oils like soybean oil, canola oil, sunflower oil, cottonseed oil and corn oil. When you consume too much omega-6, it can decrease your body’s ability to metabolize healthy omega-3 fatty acids. (36)
EPA and DHA  stand for eicosapentaenoic acid and docosahexaenoic acid respectively. These fatty acids are omega-3 fats, which are found in cold water fish. EPA DHA are highly unsaturated fats because they contain six and five double bonds on their long structural chains. These polyunsaturated fats play a very important role with the function of our bodies.
As a result, we depend on our diet to get the necessary Omega-3 fatty acids into our bodies. These two fatty acids work together in human health. DHA helps with cell membrane structure and assists in normal growth and development. While both EPA and DHA participate in key pathways of the immune system where they control key processes that support our health. Together they provide a number of important health benefits throughout our lifetime.
People with metabolic syndrome (the combination of central obesity, high blood pressure, disturbed lipid profile, and impaired glucose tolerance) are at increased risk of death from cardiovascular disease, diabetes, cancer, and other apparently “age-related” disorders. Because metabolic syndrome is closely associated with chronic low-grade inflammation, the powerful anti-inflammatory effects of omega-3 fats are especially important as a means of slowing or stopping the progression of this deadly disorder.
Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).
Boucher, O., Burden, M. J., Muckle, G., Saint-Amour, D., Ayotte, P., Dewailly, E. ... Jacobson, J. L.. (2011, May). Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. American Journal of Clinical Nutrition 93(5), 1025-1037. Retrieved from http://ajcn.nutrition.org/content/93/5/1025.full
A, Subgroup meta-analysis of the anxiolytic effect of omega-3 polyunsaturated fatty acids (PUFAs) based on an underlying specific clinical diagnosis or not. The anxiolytic effect of omega-3 PUFAs was not significant in the subgroup of participants without specific clinical conditions (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) but was significant in the subgroup of participants with specific clinical diagnoses (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01). Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFAs were significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03). B, Subgroup meta-analysis of the anxiolytic effect of omega-3 PUFAs based on different mean omega-3 PUFA dosages. The anxiolytic effect of omega-3 PUFAs was not significant in subgroups of mean omega-3 PUFA dosages less than 2000 mg/d (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) but was significant in the subgroup of mean omega-3 PUFA dosage of at least 2000 mg/d (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02).
About the only exception are wild-caught Alaskan salmon and very small fish like sardines. The highest concentrations of mercury are found in large carnivorous fish like tuna, sea bass, and marlin. You may need to be especially cautious of canned tuna as well, as independent testing by the Mercury Policy Project found that the average mercury concentration in canned tuna is far over the "safe limits" of the Environmental Protection Agency (EPA).
Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[61][62] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[63] It is under study as a candidate essential nutrient with roles in neurodevelopment, cognition, and neurodegenerative disorders.[61]
Fish oil is also extremely beneficial for pregnant women and their children. Throughout pregnancy and also while breastfeeding, a woman’s omega-3 needs are even higher than usual. According to the American Pregnancy Association, most U.S. women are deficient in EPA and especially DHA going into pregnancy and get even more depleted during pregnancy, as the placenta supplies the fetus with DHA from the mother’s tissue. Omega-3 DHA is a critical building block of the fetal brain, eyes and nervous system. Once the baby is born, omega-3s continue to be vital to healthy brain development and immune function. (30)

Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.
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.

Rogers, P. J., Appleton, K. M., Kessler, D., Peters, T. J., Gunnell, D., Hayward, R. C., Heatherley, S. V., Christian, L. M., McNaughton, S. A., and Ness, A. R. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 2008;99(2):421-431. View abstract.
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