Keck, P. E., Jr., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., Frye, M. A., Altshuler, L. L., Kupka, R., Nolen, W. A., Leverich, G. S., Denicoff, K. D., Grunze, H., Duan, N., and Post, R. M. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol.Psychiatry 11-1-2006;60(9):1020-1022. View abstract.

Kremer, J. M., Lawrence, D. A., Petrillo, G. F., Litts, L. L., Mullaly, P. M., Rynes, R. I., Stocker, R. P., Parhami, N., Greenstein, N. S., Fuchs, B. R., and . Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum. 1995;38(8):1107-1114. 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]
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
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.
“The review provides good evidence that taking long-chain omega 3 (fish oil, EPA or DHA) supplements does not benefit heart health or reduce our risk of stroke or death from any cause.  The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on cardiovascular health. On the other hand, while oily fish is a healthy food, it is unclear from the small number of trials whether eating more oily fish is protective of our hearts. 

Nielsen, G. L., Faarvang, K. L., Thomsen, B. S., Teglbjaerg, K. L., Jensen, L. T., Hansen, T. M., Lervang, H. H., Schmidt, E. B., Dyerberg, J., and Ernst, E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22(10):687-691. View abstract.
Omega AD study, Freund-Levi et al. (47) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) Decline in cognitive function did not differ between supplemented group and placebo group at 6 mo. However, patients with very mild cognitive dysfunction (n = 32, MMSE score >27) in the EPA+DHA-supplemented group had a significant reduction in MMSE score decline rate at 6 mo
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.
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.

Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
Cochrane lead author, Dr. Lee Hooper from the University of East Anglia, UK said: “We can be confident in the findings of this review which go against the popular belief that long-chain omega 3 supplements protect the heart. This large systematic review included information from many thousands of people over long periods.  Despite all this information, we don’t see protective effects.

Pro Omega 3 Intensive Formula is a more convenient source of EPA and DHA than regular marine fish oils for those who would like to supplement their diets with higher amounts of these important omega 3 fatty acids. Our formula contains concentrated marine fish oil, providing enriched levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Plus, it’s lower in saturated fatty acids than regular marine fish oil. For those who don’t eat fish or want to add more omega to their diet, Omega 3 supplements are a convenient way of incorporating these important nutrients into your everyday life. This fish oil supplement is strictly screened for the absence of any toxic metals and chemicals, and is completely free of cholesterol. The oil is carefully processed and handled to avoid oxidation.†
Fish oils might slow blood clotting. Taking fish oils along with medications that also slow clotting might increase the chances of bruising and bleeding.Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
The randomized trials assessing the efficacy of fish oil supplementation on secondary prevention of CAD lend further evidence to the findings that fish oil may protect from sudden cardiac death.36 The Diet and Reinfarction Trial (DART),37 one of the first randomized trials of fish oil in CAD, has been interpreted as potential support for fish oil’s role in sudden death reduction because the primary outcome of all-cause mortality occurred within 2 months of the trial’s onset.38 After such a short time span, it was believed that atherosclerosis would not be altered and therefore another mechanism was reducing mortality. This was further supported by the fact that nonfatal MIs were not reduced. Although the actual modes of death other than CAD-related deaths were not documented, it has been postulated to be secondary to a reduction in sudden death.39 The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Prevenzione40 (GISSI-Prevenzione) trial, a larger randomized trial of fish oil in CAD, has also been interpreted as evidence for fish oil’s protection against sudden death. Sudden death, however, was not a primary end point. Rather, the reduction in fatal events was driven by a reduction in cardiovascular death, which included coronary death, cardiac death, and sudden death.
This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.
Omega-3 [(n-3)] long-chain PUFA, including EPA and DHA, are dietary fats with an array of health benefits (1). They are incorporated in many parts of the body including cell membranes (2) and play a role in antiinflammatory processes and in the viscosity of cell membranes (3, 4). EPA and DHA are essential for proper fetal development and healthy aging (5). DHA is a key component of all cell membranes and is found in abundance in the brain and retina (6). EPA and DHA are also the precursors of several metabolites that are potent lipid mediators, considered by many investigators to be beneficial in the prevention or treatment of several diseases (7).

Heterogeneity was examined using the Q statistic and the corresponding P values,41 and the I2 statistic was used to evaluate the proportion of variation resulting from among-study differences. Any possible publication bias was detected with both funnel plots and Egger regression in the main part of the meta-analysis.42 By using Duval and Tweedie’s trim-and-fill test, we adjusted the effect sizes for potential publication bias if there was evidence of publication bias detected by this test in the Comprehensive Meta-analysis statistical software, version 3.43 To investigate the potential confounding effects of any outliers within the recruited studies, sensitivity testing was conducted with the 1-study removal method to detect the potential outliers.44

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.
Because of the preliminary state of knowledge on the effects of omega-3 PUFA treatment on anxiety, we decided to include as many studies as possible and not to set further limitations on specific characteristics, such as length of study, diagnosis, omega-3 PUFA dosage, omega-3 PUFA preparation (EPA to DHA ratio), rated anxiety coding scale, or type of control. Therefore, we chose to make the inclusion criteria as broad as possible to avoid missing any potentially eligible studies. The inclusion criteria included clinical trials in humans (randomized or nonrandomized), studies investigating the effects of omega-3 PUFA treatment on anxiety symptoms, and formal published articles in peer-reviewed journals. The clinical trials could be placebo controlled or non–placebo controlled. The target participants could include healthy volunteers, patients with psychiatric illness, and patients with physical illnesses other than psychiatric illnesses. The exclusion criteria included case reports or series, animal studies or review articles, and studies not investigating the effects of omega-3 PUFA treatment on anxiety symptoms. We did not set any language limitation to increase the number of eligible articles. Figure 1 shows the literature search and screening protocol.
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.
After a large number of lab studies found that omega-3 fatty acids may be effective in slowing or reversing the growth of hormonal cancers, namely prostate and breast cancer cells, animal and human epidemiological studies have been conducted to see whether this effect occurred in real-life scenarios. The evidence is somewhat conflicting in some reports, but there is some evidence to suggest breast and prostate cancers may be potentially slowed (or the risk reduced) in people who eat a lot of oily fish and possibly those who supplement with omega-3. (66, 67, 68)
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]
In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. (5)

Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the source of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass fed animals.[134] When cattle are taken off omega−3 fatty acid rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[135]
More than 30 clinical trials have tested different omega-3 preparations in people with depression. Most studies have used omega-3s as add-on therapy for people who are taking prescription antidepressants with limited or no benefit. Fewer studies have examined omega-3 therapy alone. Clinical trials typically use EPA alone or a combination of EPA plus DHA, at doses from 0.5 to 1 gram per day to 6 to 10 grams per day. To give some perspective, 1 gram per day would correspond to eating three salmon meals per week.
Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16
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.
This under-the-radar grain is a nutritional powerhouse — and one of the most potent sources of the omega-3 alpha-Linolenic acid (ALA). Sprinkle flaxseeds over your morning oatmeal for a pleasant nutty flavor, or blend them into fruit smoothies to satisfy a picky palate. Need more ideas? Check out The Flaxseed Recipe Book, an easy-to-follow guide for adding flaxseeds to your favorite soups, salads, and main courses.

The strongest evidence for a beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. (1) Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis. (1)


Fish oil has the ability to treat Attention Deficit Hyperactivity Disorder (ADHD) due to its high concentration of fatty acids. For children suffering from hyperactivity, dyslexia, dyspraxia, inability to complete tasks, emotional instability, wavering attitude, poor coordination, short attention span, short-term memory weakness, low concentration, tendency to interrupt others, recklessness, hastiness, impetuosity, impulsiveness, low IQ, or learning disorders, fish oil is a proven remedy. Research conducted at the University of South Australia and CSIRO has shown that when children suffering from ADHD were given doses of fish oil and evening primrose capsules for 15 weeks, they showed significant improvements in their behavior. Since, human brain consists of about 60% fats, especially essential fatty acids such as omega-3 and omega-6, it helps to improve the functions of the brain.
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.
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).
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.
So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)
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.
Many studies documenting the benefits of omega-3s have been conducted with supplemental daily dosages between 2 and 5 grams of EPA and DHA, more than you could get in 2 servings of fish a week. But that doesn't mean eating fish is an exercise in futility. Many studies document its benefits. For example, a 2003 National Eye Institute study showed that 60- to 80-year-olds eating fish more than twice a week were half as likely to develop macular degeneration as those who ate no fish at all.
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.
Weight loss. Some research shows that eating fish improves weight loss and decreases blood sugar in people who are overweight with high blood pressure. Early research also shows that taking a specific fish oil supplement (Hi-DHA, NuMega) lowers body fat when combined with exercise. But other evidence suggests that taking another specific fish oil supplement (Lovaza) does not lower body weight in overweight people.
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