“This idea has since been pretty discredited; we really don’t know if the Eskimos got heart disease or not,” said Malden C. Nesheim, emeritus professor of nutrition at Cornell University, who chaired an Institute of Medicine committee assessing the risks and benefits of seafood in the early 2000s. “I’ve been an omega-3 skeptic since doing this study.”

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. 
Additional side effects of fish oil supplements which have been reported include headache, short-term memory loss, depression, somatic disorders, and increased risk of colon cancer, nasopharyngitis, worsening of asthma symptoms, hemolytic anemia, decreased physical activity, increased appetite, a general uncomfortable feeling or increased blood pressure. The percentage of users that develop these side effects is not known. If these side effects become severe it is recommended that you stop using fish oil supplements.
Krauss-Etschmann, S., Hartl, D., Rzehak, P., Heinrich, J., Shadid, R., Del, Carmen Ramirez-Tortosa, Campoy, C., Pardillo, S., Schendel, D. J., Decsi, T., Demmelmair, H., and Koletzko, B. V. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J.Allergy Clin.Immunol. 2008;121(2):464-470. View abstract.
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
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.
Although there are no randomized data on fish oil consumption and protection from sudden death, observational studies have linked omega-3 FA with the prevention of sudden death. In a population-based, case-control study of sudden cardiac death victims, the mean red blood cell membrane omega-3 FA level of the lowest quartile, when compared with the mean level of the third quartile, was associated with a relative risk reduction of 70%.33 A similar finding was appreciated in a nested, prospective, case-control study of the Physician Health Study cohort of 22,000 healthy males. In the 119 patients that succumbed to sudden death, baseline omega-3 FA blood levels were significantly lower than in matched controls.34 Finally, in an analysis of data from the Nurses Health Study, a cohort study of 84,688 women, an inverse association was shown between fish consumption and CAD-related death. The investigators concluded that the reduction in CAD deaths was likely due to a reduction in sudden deaths, as there was no difference in the rate of MI when comparing high and low fish consumption.35
Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
Science is dynamic, not static, and as scientific understanding advances scientists sometimes have to modify their positions. Dr. Kidd’s position on EPA and DHA has now changed due to advances in the clinical and basic scientific research. Though the brain carries predominantly DHA and very little EPA, clinical trial results clearly indicate EPA has benefit for mood and probably other higher brain functions. At the basic science level, it has become clear that both EPA and DHA, not DHA alone, are required for the brain to make new nerve cells. Dr. Kidd very closely monitors the research on EPA and… Read more »

The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.
Egert, S., Somoza, V., Kannenberg, F., Fobker, M., Krome, K., Erbersdobler, H. F., and Wahrburg, U. Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr 2007;61(3):314-325. View abstract.
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.
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.

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.
Krauss-Etschmann, S., Hartl, D., Rzehak, P., Heinrich, J., Shadid, R., Del, Carmen Ramirez-Tortosa, Campoy, C., Pardillo, S., Schendel, D. J., Decsi, T., Demmelmair, H., and Koletzko, B. V. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J.Allergy Clin.Immunol. 2008;121(2):464-470. View abstract.
The human body does not produce significant amounts of EPA or DHA on its own, so you must get these important nutrients from the foods you eat and the supplements you consume. If you’re looking to get the heart health benefits of omega-3s, go straight to the source of EPA and DHA. EPA and DHA are naturally found in marine sources, including fatty fish – salmon, tuna, mackerel, herring – shellfish, and marine algae.
The most widely available dietary source of EPA and DHA is cold-water oily fish, such as salmon, herring, mackerel, anchovies, and sardines. Oils from these fish have a profile of around seven times as much omega-3 oils as omega-6 oils. Other oily fish, such as tuna, also contain omega-3 in somewhat lesser amounts. Although fish is a dietary source of omega-3 oils, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[22]

Several studies confirmed the benefit of omega-3 supplementation during pregnancy in terms of proper development of the brain and retina. Of the 2 most important long-chain omega-3 fatty acids, EPA and DHA, DHA is the more important for proper cell membrane function and is vital to the development of the fetal brain and retina (17). During the third trimester, vast amounts of DHA accumulate in fetal tissue (20). The 2 most infiltrated fetal areas include the retina and brain, which may correlate with normal eyesight and brain function (19). A study by Judge et al. (20) found that children whose mothers had taken DHA supplementation during pregnancy (n = 29) had significantly better problem-solving skills at 9 mo old (P = 0.017) than those whose mothers had not taken DHA supplementation during pregnancy (n = 15). Another study provided a cognitive assessment of children 2.5 y after maternal EPA+DHA supplementation during pregnancy from 20 wk of gestation until delivery (n = 33) compared with children in a placebo group (n = 39). Children in the EPA + DHA–supplemented group attained significantly higher scores for eye and hand coordination [mean score, 114 (SD 10.2] than those in the placebo group [mean score, 108 (SD 11.3)] (P = 0.021, adjusted P = 0.008) (19).

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.
Further, according to subgroup results based on the presence of specific clinical diagnoses or not, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. Among 6 studies included in a meta-analysis of the effect of omega-3 PUFAs on depressive symptoms, the analysis showed a nearly null effect of omega-3 PUFAs on depressive symptoms in healthy participants.73 Although the reason for the null effect of omega-3 PUFAs on anxiety and depressive symptoms remains unclear, certain pathophysiological conditions might be required for omega-3 PUFAs to exert an association of treatment with reduced anxiety symptoms.

It’s no surprise that fish — particularly cold-water fatty fish like salmon, mackerel, and anchovies — are rich in omega-3s. It’s called fish oil for a reason, right? Mackerel, for instance, may have more than 3300 mg of omega-3 per serving — that’s more than 6 times the recommended per day dose for healthy adults. Not a huge fish connoisseur? Try some of the quick, simple recipes in Cooking with Fish Like a Pro, an accessible collection of fish recipes to suit every palate.

Age-related macular degeneration (AMD) is an eye disease that can cause vision loss in older people. Two major National Institutes of Health (NIH)-sponsored studies, called Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2), showed that dietary supplements containing specific combinations of vitamins, antioxidants, and zinc helped slow the progression of AMD in people who were at high risk of developing the advanced stage of this disease. AREDS2, which had more than 4,000 participants and was completed in 2013, also tested EPA and DHA. The results showed that adding these omega-3s to the supplement formulation didn’t provide any additional benefits. Other, smaller studies of omega-3 supplements also haven’t shown them to have a beneficial effect on the progression of AMD. 
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.
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]
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
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.