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]
Saito, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008;200(1):135-140. View abstract.
Ramakrishnan, U., Stein, A. D., Parra-Cabrera, S., Wang, M., Imhoff-Kunsch, B., Juarez-Marquez, S., Rivera, J., and Martorell, R. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull 2010;31(2 Suppl):S108-S116. View abstract.
Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids – cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body’s immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.
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.
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.

Between the ages of five and 65, the majority of the body’s needs can be met by using EPA-rich oils and eating fish, marine products, organic greens and pastured animal products. EPA levels are under constant demand and low EPA levels in adolescents and adults correlates strongly with development of mental health issues, including depression, dyslexia and dyspraxia, heart problems, joint and bone conditions, as well as neurodegenerative diseases such as MS and Parkinson’s. EPA also protects our genes and cell cycle, as well as helping to keep our stress response regulated, so an adequate supply of EPA throughout adult life can help prevent a range of chronic illness.
Not all forms of fish oil may be equally digestible. Of four studies that compare bioavailability of the glyceryl ester form of fish oil vs. the ethyl ester form, two have concluded the natural glyceryl ester form is better, and the other two studies did not find a significant difference. No studies have shown the ethyl ester form to be superior, although it is cheaper to manufacture.[114][115]
Omega-3 fatty acids are frequently in the news regarding their health benefits (or doubts in some cases). Two types of omega-3s in particular - eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) – are known to be essential fatty acids. “Essential” refers to the fact that our cells need these fatty acids in order to function normally. But the body cannot make them from other fats, which means it’s “essential” we supply them in our diet or through supplementation.
Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
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]

Omega-3 fats may also impact the development of arthritis. As far back as 1959, studies were published about the effectiveness of cod liver oil on arthritic patients. In the 1959 study, 93 percent of participants “showed major clinical improvement.” (73) While there is no evidence that high omega-3 levels can prevent the development of arthritis, it seems clear that they can reduce inflammation that causes the typical bone and joint pain experienced in the disease. (74)

These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]


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.

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.
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.
^ 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]
Fish oil contains two very important omega-3 PUFAs. I’m talking about docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA are sometimes called the marine omega-3s because they mainly come from fish. Some of the best fish to eat to obtain fish oil from in your diet include wild-caught salmon, herring, white fish, sardines and anchovies.
AMA Manual of Style Art and Images in Psychiatry Breast Cancer Screening Guidelines Colorectal Screening Guidelines Declaration of Helsinki Depression Screening Guidelines Evidence-Based Medicine: An Oral History Fishbein Fellowship Genomics and Precision Health Health Disparities Hypertension Guidelines JAMA Network Audio JAMA Network Conferences Med Men Medical Education Opioid Management Guidelines Peer Review Congress Research Ethics Sepsis and Septic Shock Statins and Dyslipidemia Topics and Collections
To reach the required dose of EPA for treating certain conditions such as depression, CVD or CFS/ME you would need to take approximately 1-2 grams of ‘free EPA’ daily. Even with a concentrated omega-3 fish oil supplement, offering 180 mg excess EPA over DHA, this would require 10-20 capsules daily – significant in terms of volume and cost, and not efficient in terms of uptake in the body as our capacity for fat absorption is limited. The most effective and efficient way to ensure high EPA uptake in the body rapidly is to supplement with pure EPA for a minimum of 3-6 months.
The evidence that fish oil consumption should be used for primary prevention of CAD is based on observational studies. The only randomized trial for primary prevention, the JELIS trial, showed a moderate relative risk reduction and was conducted in a very specific group. Nevertheless, to date, there has been no strong signal suggesting any serious adverse effects of having high DHA and EPA oils in the diet. We agree with the national guidelines that one should consume moderate amounts of fish oil— either in supplement or through the dietary intake of fatty fish with low mercury levels.
Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
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

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.


Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).
Jump up ^ Naliwaiko, K.; Araújo, R.L.F.; Da Fonseca, R.V.; Castilho, J.C.; Andreatini, R.; Bellissimo, M.I.; Oliveira, B.H.; Martins, E.F.; Curi, R.; Fernandes, L.C.; Ferraz, A.C. (2004). "Effects of Fish Oil on the Central Nervous System: A New Potential Antidepressant?". Nutritional Neuroscience. 7 (2): 91–99. doi:10.1080/10284150410001704525. PMID 15279495.
Gorjao, R., Verlengia, R., Lima, T. M., Soriano, F. G., Boaventura, M. F., Kanunfre, C. C., Peres, C. M., Sampaio, S. C., Otton, R., Folador, A., Martins, E. F., Curi, T. C., Portiolli, E. P., Newsholme, P., and Curi, R. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006;25(6):923-938. View abstract.
Today, the average American has a 20:1 ratio of omega-6 to omega-3 fats, when a healthy ratio is more ideally around 2:1. Put in other numerical terms, the typical American diet tends to contain 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids. (35) This shows just how deficient most of us are and why supplementing with fish oil is so beneficial.

Irish AB, Viecelli AK, Hawley CM, et al; Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial. JAMA Intern Med. 2017;177(2):184-193. View abstract.
Bell, J. G., Miller, D., MacDonald, D. J., MacKinlay, E. E., Dick, J. R., Cheseldine, S., Boyle, R. M., Graham, C., and O'Hare, A. E. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr 2010;103(8):1160-1167. View abstract.
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
Oftentimes this could be a result of poor body composition, poor activity levels, or other things, like a low-quality diet. Now, for other people, I do think it’s the case that for people who do not eat fish and for people whose animal products, especially their eggs, are mostly from animals fed grains rather than pasture-raised animals or who don’t eat eggs, I think in those cases there is an argument for fish oil in the sense that those people are probably not going to get enough omega-3 fatty acids, but the better argument might be: Eat pastured eggs or eat fish. Even eating an oily fish like salmon once or twice a week is probably good enough to provide the omega-3 fatty acids that you need. Eating some pastured egg yolks every day is probably good enough to provide for the omega-3 fatty acids that you need.
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.
van der Meij, B. S., Langius, J. A., Smit, E. F., Spreeuwenberg, M. D., von Blomberg, B. M., Heijboer, A. C., Paul, M. A., and van Leeuwen, P. A. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J.Nutr. 2010;140(10):1774-1780. View abstract.
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.

The current American diet has changed over time to be high in SFA and low in omega-3 fatty acids (12). This change in eating habits is centered on fast food containing high amounts of saturated fat, which has small amounts of essential omega-3 PUFA compared with food prepared in the home (13). Seafood sources such as fish and fish-oil supplements are the primary contributors of the 2 biologically important dietary omega-3 fatty acids, EPA and DHA (14–16). This low intake of dietary EPA and DHA is thought to be associated with increased inflammatory processes as well as poor fetal development, general cardiovascular health, and risk of the development of Alzheimer's disease (AD).
There was a significantly greater association of treatment with reduced anxiety symptoms in participants receiving omega-3 PUFAs than in those not receiving omega-3 PUFAs in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g, 0.485; 95% CI, 0.017-0.954; P = .04; Figure 4)35,49,52,54-61 but 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 subgroup with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35) (Figure 4).33,34,36,47,48,50,51,53,60 There were no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .13).

De Truchis, P., Kirstetter, M., Perier, A., Meunier, C., Zucman, D., Force, G., Doll, J., Katlama, C., Rozenbaum, W., Masson, H., Gardette, J., and Melchior, J. C. Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study. J.Acquir.Immune.Defic.Syndr. 3-1-2007;44(3):278-285. View abstract.

Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23

Lok CE, Moist L, Hemmelgarn BR, Tonelli M, Vazquez MA, Dorval M, Oliver M, Donnelly S, Allon M, Stanley K; Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) Study Group. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA 2012;307(17):1809-16. View abstract.
Dry eye. Some clinical research shows that eating more fish oil is linked to a lower risk of getting dry eye syndrome in women. Other research shows that taking a specific fish oil product (PRN Dry Eye Omega Benefits softgels) daily modestly improves symptoms of dry eye such as pain, blurred vision, and sensitivity. Other research using other forms of fish oil products suggests that taking these supplements for 4-12 weeks modest improves some dry eye symptoms. However, the sensation of eye dryness is not always improved. Other research also shows that taking a specific combination products containing fish oil and other ingredients might improve some dry eye symptoms; however, this research is conflicted and poor quality.

This article had several limitations and the findings need to be considered with caution. First, our participant population is too heterogeneous because of our broad inclusion criteria, which might be true if considering current Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases diagnostic systems. However, the novel Research Domain Criteria consider anxiety to be one of the major domains in Negative Valence Systems. Trials should be conducted in populations in which anxiety is the main symptom irrespective of the presence or absence of diagnosis of anxiety disorder. Second, because of the limited number of recruited studies and their modest sample sizes, the results should not be extrapolated without careful consideration. Third, the significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) with potential influence by some outlier studies, such as the studies by Sohrabi et al56 and Yehuda et al,61 would be another major concern. Therefore, clinicians should pay attention to this aspect when applying the results of the current meta-analysis to clinical practice, particularly when considering the subgroups of these 2 studies (ie, subgroups with specific clinical diagnoses, with <2000 mg/d, with EPA <60%, and with placebo-controlled trials).
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)
Cancer. Research on the effects of fish oil in preventing cancer has produced conflicting results. Some population research suggests that eating fish or having higher blood levels of omega-3 fatty acids from fish oil is linked to a lower risk of different cancers, including oral cancer, pharyngeal cancer, esophageal cancer, colon cancer, rectal cancer, breast cancer, ovarian cancer, and prostate cancer. But other research suggests that eating fish does not reduce the risk of cancer.
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