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.
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
Evidence in the population generally does not support a beneficial role for omega−3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death) or stroke.[4][19][20][21] A 2018 meta-analysis found no support that daily intake of one gram of omega-3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.[6] However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.[22] No protective effect against the development of stroke or all-cause mortality was seen in this population.[22] Eating a diet high in fish that contain long chain omega−3 fatty acids does appear to decrease the risk of stroke.[23] Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.[24] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[7]

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

Oe, H., Hozumi, T., Murata, E., Matsuura, H., Negishi, K., Matsumura, Y., Iwata, S., Ogawa, K., Sugioka, K., Takemoto, Y., Shimada, K., Yoshiyama, M., Ishikura, Y., Kiso, Y., and Yoshikawa, J. Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Heart 2008;94(3):316-321. 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. 

It exists in nature in three forms, one derived from land plants and two derived from marine sources. In the body, omega-3 is highly concentrated in the brain; it is critical to the formation and maintenance of nerve cell membranes. Research shows that in the nervous system, omega-3s foster the development of brain circuitry and the processing of information. They also play important roles in stabilizing mood and staving off cognitive decline. Low levels of omega-3s are linked to poor memory and depression. Omega-3 fats are also critical for the formation of anti-inflammatory molecules in the body.
Luo, J Rizkalla SW Vidal H Oppert JM Colas C Boussairi A Guerre-Millo M Chapuis AS Chevalier A Durand G Slama G. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. 1998;21(5):717-724. View abstract.

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

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]
Alpha-linolenic Acid (ALA): This plant-based omega-3 is found in green, leafy vegetables, flaxseeds, chia seeds and canola, walnut and soybean oils (although those rancid oils are not ones I generally recommend). ALA is known as a short-chain omega-3, meaning your body has to convert it into longer-chained EPA and DHA to synthesize it. This process is rather inefficient and only about one percent of the ALA you consume is converted to the long-chain version your body needs (although this percentage is slightly higher for women).
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]

Carrero, J. J., Fonolla, J., Marti, J. L., Jimenez, J., Boza, J. J., and Lopez-Huertas, E. Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program. J.Nutr. 2007;137(2):384-390. 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]
Oe, H., Hozumi, T., Murata, E., Matsuura, H., Negishi, K., Matsumura, Y., Iwata, S., Ogawa, K., Sugioka, K., Takemoto, Y., Shimada, K., Yoshiyama, M., Ishikura, Y., Kiso, Y., and Yoshikawa, J. Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Heart 2008;94(3):316-321. View abstract.

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 US National Institutes of Health lists three conditions for which fish oil and other omega-3 sources are most highly recommended: hypertriglyceridemia (high triglyceride level), preventing secondary cardiovascular disease, and hypertension (high blood pressure). It then lists 27 other conditions for which there is less evidence. It also lists possible safety concerns: "Intake of 3 grams per day or greater of omega-3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil/omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke."[12]
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!
An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)

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)
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]

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.


Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
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).

46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]


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.
The GISSI-Prevenzione trial40 showed similar findings. In this open-label trial, 11,324 post-MI patients were followed for 3.5 years after randomization to either 1 g/d of omega-3 FA, vitamin E, both, or none. In the 2836 patients assigned to only omega-3 FA, the primary end point of death, nonfatal MI or stroke, was reduced by 10%. This decreased risk occurred despite a minimal triglyceride-lowering effect because of the relatively low dose of omega-3 FA. Of note, the GISSI-Prevenzione trial was done prior to the pervasive use of lipid-lowering agents. Only about 40% of patients were on any form of lipid-lowering therapy.
Another study conducted by researchers at Rhode Island Hospital examined the relationship between fish oil supplementation and indicators of cognitive decline. The subjects of the study were older adults: 229 cognitively normal individuals, 397 patients with mild cognitive impairment and 193 patients with Alzheimer’s disease. They were assessed with neuropsychological tests and brain magnetic resonance imaging every six months while taking fish oil supplements. The study found that the adults taking fish oil (who had not yet developed Alzheimer’s and did not have genetic risk factor for developing Alzheimer’s known as APOE ε4) experienced significantly less cognitive decline and brain shrinkage than adults not taking fish oil. (9)
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.

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.
In comparison, the omega-3s found in krill appear to be more rapidly incorporated into red blood cell phospholipids.7 This is important, because not only do scientists view the uptake of essential fatty acids in red blood cells as a biomarker for uptake into the brain,8 but additional research suggests that when omega-3 fatty acids such as DHA are bound to phospholipids as they are with krill, it increases their uptake to the brain.9 This is further supported by human clinical research, which suggests ingestion of phospholipid-bound EPA and DHA increase cognitive function scores to a greater degree compared with scores obtained when the fatty acids in the ingested oil were provided in the triglycerides storage form.10
Henriksen, C., Haugholt, K., Lindgren, M., Aurvag, A. K., Ronnestad, A., Gronn, M., Solberg, R., Moen, A., Nakstad, B., Berge, R. K., Smith, L., Iversen, P. O., and Drevon, C. A. Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 2008;121(6):1137-1145. View abstract.
Bemelmans, W. J., Broer, J., Feskens, E. J., Smit, A. J., Muskiet, F. A., Lefrandt, J. D., Bom, V. J., May, J. F., and Meyboom-de Jong, B. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr 2002;75(2):221-227. View abstract.
Good for you for eating healthily! Sadly, many people do not like omega-3 containing foods such as fish, and for these people, supplementation may be a good alternative to obtain omega-3. As a clinical investigator, my research focuses on study supplements, which is what I was asked to cover in this article. I’m all for healthy eating, but not everyone can afford it or wants to eat certain foods, and this is perhaps why supplements are so popular.

Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.


Damage to the kidneys caused the drug cyclosporine. Cyclosporine is a medication that reduces the chance of organ rejection after an organ transplant. Taking fish oil seems to prevent kidney damage in people taking this drug. Fish oil also seems to improve kidney function during the recovery phase following the rejection of a transplanted organ in people taking cyclosporine.
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