16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. 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;200:135–40. [PubMed]
Nonetheless, large population studies with solid data both on the participants’ diets and causes of disease and death bolstered the beliefs that eating fish often was a heart-healthy practice linked to reduced rates of cardiovascular disease. For example, a comprehensive analysis conducted by Dr. Dariush Mozaffarian and Eric Rimm of the Harvard T.H. Chan School of Public Health found that eating two servings of fatty fish a week — equal to about two grams of omega-3 fatty acids — lowered the risk of death from heart disease by more than a third and total deaths by 17 percent.

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According to the 2012 National Health Interview Survey, which included a comprehensive survey on the use of complementary health approaches in the United States, fish oil supplements are the nonvitamin/nonmineral natural product most commonly taken by both adults and children. The survey findings indicated that about 7.8 percent of adults (18.8 million) and 1.1 percent of children age 4 to 17 (664,000) had taken a fish oil supplement in the previous 30 days.
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

A study published in Brain Research shows how far-reaching fish oil can be for people with diabetes. Researches found that fish oil can help reduce the risk of diabetics from developing cognitive deficit because it protects the hippocampus cells from being destroyed. The study also showed that fish oil could help reduce oxidative stress, which plays a central role in the development of diabetes complications, both microvascular and cardiovascular. (22)
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.

In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.

Omega AD study, Irving et al. (54) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo, then for all subjects (supplementation group and placebo group) Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the placebo group, and for both groups at 12 mo
The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Finally, it is often assumed since there are not high levels of EPA in the brain, that it is not important for neurological function. Actually it is key for reducing neuro-inflammation by competing against AA for access to the same enzymes needed to produce inflammatory eicosanoids. However, once EPA enters into the brain it is rapidly oxidized (2,3). This is not the case with DHA (4). The only way to control cellular inflammation in the brain is to maintain high levels of EPA in the blood. This is why all the work on depression, ADHD, brain trauma, etc. have demonstrated EPA to be superior to DHA (5).
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.

Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 

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]
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
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)
I now suspect that those thousands of gel-covered capsules I’ve swallowed over the years may have done little more than enrich the pockets of supplement producers and sellers. A number of extensive analyses have been conducted, some supporting and others refuting the value of fish oils to the cardiovascular system, along with studies of other purported health benefits that also have had mixed results.
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.
However, this difference in the length of the carbon chain gives these two types of omega-3s significant characteristics. EPA and DHA are long-chain fatty acids, while ALA is a short-chain fatty acid. The long-chain fatty acids are more important for cellular health. Another omega-3 fat, docosapentaenoic acid (DPA) can also be better synthesized by your body by elongating EPA.
When it comes to omega-3 benefits, there are rarely nutrients that pack this many positive health outcomes into one compound. The most commonly known benefit of omega-3s is a reduced risk of heart disease, but that’s not the only studied plus of getting lots of omega-3s in your diet — from fetal development to retinal function to weight management (and a lot more in between), these acids support and promote optimal health for anyone. (1)
Docosahexaenoic acid (DHA) found primarily in fish oil, this is the ultimate form of fatty acid in humans. Most people get far too little of this all-important fatty acid, especially since the conversion of ALA to DHA is slow and minimally yielding. Getting a daily dose of of DHA (600 to 1000 mg) from supplements is preferable to reap the health benefits. You have a choice of taking a fish oil supplement or one derived from algae or krill, a shrimp-like crustacean.
Guallar, E., Aro, A., Jimenez, F. J., Martin-Moreno, J. M., Salminen, I., van't Veer, P., Kardinaal, A. F., Gomez-Aracena, J., Martin, B. C., Kohlmeier, L., Kark, J. D., Mazaev, V. P., Ringstad, J., Guillen, J., Riemersma, R. A., Huttunen, J. K., Thamm, M., and Kok, F. J. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler.Thromb.Vasc.Biol 1999;19(4):1111-1118. View abstract.
The most widely available dietary source of EPA and DHA is oily fish, such as salmon, herring, mackerel, anchovies, menhaden, and sardines. Oils from these fish have a profile of around seven times as much omega−3 as omega−6. Other oily fish, such as tuna, also contain n-3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) [110] reported that the benefits of fish intake generally far outweigh the potential risks. Although fish are a dietary source of omega−3 fatty acids, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[111] In the case of farmed fish, omega-3 fatty acids is provided by fish oil; In 2009, 81% of the global fish oil production is used by aquaculture.[112]
Cast about for healthy canned tuna. Think all tuna is created equal? Think again. Choose canned light tuna instead of tuna steaks or albacore tuna. It tends to have less mercury. Albacore may contain three times the mercury of chunk light tuna. Check fish guides for the latest information about foods low in toxins but high in omega-3. Two good online sources are:
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.
Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.
Your body can convert some ALA into EPA and then DHA, but not enough to meet all your body’s needs but the best way to assure you are getting enough heart healthy fats is to eat foods high in the omega 3 fats, and if you can’t or don’t get enough of these necessary fats in your diet, you might consider taking an omega 3 supplement to boost these needed fats. More on this later.
Augood, C., Chakravarthy, U., Young, I., Vioque, J., de Jong, P. T., Bentham, G., Rahu, M., Seland, J., Soubrane, G., Tomazzoli, L., Topouzis, F., Vingerling, J. R., and Fletcher, A. E. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr 2008;88(2):398-406. View abstract.
Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.
Nine studies with 10 data sets used omega-3 PUFA dosages of less than 2000 mg/d.35,47,48,51,53,55,56,60,61 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) (Figure 3B). Ten studies with 10 data sets used omega-3 PUFA dosages of at least 2000 mg/d.33,34,36,49,50,52,54,55,57-59 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02) (Figure 3B). Furthermore, there was no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .40).
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.
1. Omega-3 benefits your heart health. An Italian study (GISSI)5 of 11,324 heart attack survivors found that patients supplementing with fish oils markedly reduced their risk of another heart attack, stroke, or death. In a separate study, 6 American medical researchers reported that men who consumed fish once or more every week had a 50 percent lower risk of dying from a sudden cardiac event than do men who eat fish less than once a month.
The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.

Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.
Smithers, L. G., Collins, C. T., Simmonds, L. A., Gibson, R. A., McPhee, A., and Makrides, M. Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial. Am J Clin Nutr 2010;91(3):628-634. View abstract.
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.
Fortier, M., Tremblay-Mercier, J., Plourde, M., Chouinard-Watkins, R., Vandal, M., Pifferi, F., Freemantle, E., and Cunnane, S. C. Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Quebec: higher fish intake or aging-related change in n-3 fatty acid metabolism? Prostaglandins Leukot.Essent.Fatty Acids 2010;82(4-6):277-280. View abstract.
Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly inroe oil and green-lipped mussel and is only recently being recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead!
Hamazaki, K., Itomura, M., Huan, M., Nishizawa, H., Sawazaki, S., Tanouchi, M., Watanabe, S., Hamazaki, T., Terasawa, K., and Yazawa, K. Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Nutrition 2005;21(6):705-710. View abstract.
Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.

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. 

Heart disease. Research suggests that eating fish can be effective for keeping people with healthy hearts free of heart disease. People who already have heart disease might also be able to lower their risk of dying from heart disease by eating fish. The picture is less clear for fish oil supplements. For people who already take heart medications such as a "statin" and those who already eat a decent amount of fish, adding on fish oil might not offer any additional benefit.
After the age of five, the development of the brain and CNS starts to reduce and the body’s need for DHA reduces. This is a good time to increase EPA in the diet, as studies show that EPA can help with childhood behaviour and academic performance, as well as focus, attention and reducing aggression. Dry skin conditions, asthma and allergies are also common in children and good levels of EPA at this time can help reduce the inflammation associated with these issues.
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]
Gerber, J. G., Kitch, D. W., Fichtenbaum, C. J., Zackin, R. A., Charles, S., Hogg, E., Acosta, E. P., Connick, E., Wohl, D., Kojic, E. M., Benson, C. A., and Aberg, J. A. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J.Acquir.Immune.Defic.Syndr. 4-1-2008;47(4):459-466. View abstract.
In a U.K. study, children of mothers who ate more than 12 ounces a week actually scored better on tests of verbal I.Q., social behavior, and development and communication than children of mothers who ate none. In the Seychelles Islands, where people average 12 fish meals -- not ounces -- a week, there are no reports of links between mercury exposure and poor outcomes in children. These studies suggest that eating less than 12 ounces of fish each week could do more harm to a child's developing neurological system than mercury poisoning.
Those foods provide enormous amounts of other nutrients that are good for you. nSo it is way better to eat those foods than to take fish oil. With that said, some people find it very difficult to get vitamin A or vitamin D, and particularly for vitamin A, cod liver oil may be a very important source of that vitamin. Cod liver oil is a form of fish oil that happens to be high in the fat-soluble vitamins. Vitamin A is best found in liver. It’s better in my opinion to eat liver once a week, but there are a lot of people out there who are not going to eat liver once a week. So if you are using cod liver oil to get the vitamins that you can’t get from food—and I should point out that vitamin A can also be derived from plant foods, but many people genetically or for other reasons don’t derive it very well from plant foods.
The omega-3 index may also be helpful for assessing health risks beyond cardiovascular disease. Studies are currently investigating the relationship between omega-3 index levels and mental health issues, like depression (15, 16, 17), cognitive functioning (18, 19), body weight (20), as well as eye health issues, like macular degeneration (21), to name just a few.
The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
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.
We hypothesized that omega-3 PUFAs might have anxiolytic effects in patients with significant anxiety- and fear-related symptoms. However, there have been no systematic reviews of this topic to date. Thus, we examined the anxiolytic effects of omega-3 PUFAs in participants with elevated anxiety symptoms in the results of clinical trials to determine the overall efficacy of omega-3 PUFAs for anxiety symptoms irrespective of diagnosis.
Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.
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.
If you have a bleeding disorder, bruise easily or take blood-thinning medications, you should use fish oil supplements with extra caution since large doses of omega-3 fatty acids can increase bleeding risk. This bleeding risk also applies to people with no history of bleeding disorders or current medication usage. If you have type 2 diabetes, you should only use fish oil supplements under your doctor’s supervision. Individuals with type 2 diabetes can experience increases in fasting blood sugar levels while taking fish oil supplements.
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.
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.