Gajos G1, Rostoff P, Undas A, et al. 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 Apr 20;55(16):1671-8. View abstract.


The National Institutes of Health (NIH) has created a website, NIH Clinical Research Trials and You, to help people learn about clinical trials, why they matter, and how to participate. The site includes questions and answers about clinical trials, guidance on how to find clinical trials through ClinicalTrials.gov and other resources, and stories about the personal experiences of clinical trial participants. Clinical trials are necessary to find better ways to prevent, diagnose, and treat diseases.
Since 2004, scientists have been suggesting that the omega-3 index be used as a way to measure a person’s risk of cardiovascular disease, in a similar way to how cholesterol levels are used today (1). A recent study funded by the National Institutes for Health even indicated that the omega-3 index could be a better predictor of death risk than serum cholesterol levels (2).
Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)

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]
“Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine.” We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.
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
The Department of Ecology of the State of Washington has ranked various seafood based on its EPA and DHA concentrations. The highest-ranking seafood is mackerel, excluding King mackerel, that has a concentration of 1,790 milligrams of combined EPA and DHA per 100 grams, followed by salmon at 1,590; bluefin tuna has between 1173 and 1504 milligrams; sardines contain 980 milligrams; albacore tuna has 862 milligrams; bass has 640 milligrams; tuna has 630 milligrams; trout and swordfish have 580 milligrams; and walleye has 530 milligrams. Other seafood, which includes sea bass, clams, lobster, scallops, catfish, cod, pollock, crayfish and scallops contains between 200 and 500 milligrams of EPA and DHA per 100 grams. Breaded fish products rank lowest on the list with only 0.26 milligram per 100 grams.
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.
Jump up ^ Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S (May 2011). "Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association". Circulation. 123 (20): 2292–333. doi:10.1161/CIR.0b013e3182160726. PMID 21502576.
In total, 19 articles with 19 data sets revealed the main results of the meta-analysis, namely that there was a significantly better association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 19; Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01; Figure 2), with significant heterogeneity (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) but no significant publication bias via Egger regression (t, 1.736; df, 17; P = .10) or inspection of the funnel plot (eFigure 2 in the Supplement). According to the trim-and-fill test, there was no need for adjustment for publication bias. The meta-analysis results remained significant after removal of any one of the included studies, which indicated that the significant results are not owing to any single study.
In a 2009 letter on a pending revision to the Dietary Guidelines for Americans, the American Heart Association recommended 250–500 mg/day of EPA and DHA.[26] The Guidelines were revised again for 2015-2020; included is a recommendation that adults consume at least eight ounces of a variety of types of fish per week, equating to at least 250 mg/day of EPA + DHA.[citation needed] The Food and Drug Administration recommends not exceeding 3 grams per day of EPA + DHA from all sources, with no more than 2 grams per day from dietary supplements.[27]

Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]

In some cases, fish oil pills may cause loose stools, nausea, diarrhea, and decreased appetite, fat in the stools, vomiting or constipation. These side effects can be minimized by taking a fish oil capsule that is coated, which is designed to help eliminate the "fish burps" many users complain about. Starting with low doses of the supplement and working up to a full dose can also help minimize side effects. You can also pair fish oil supplements with meals so that they enter your body more slowly, minimizing the risk of side effects occurring.
Your retina contains quite a bit of DHA, making it necessary for that fatty acid to function. (90) The National Eye Institute, part of the National Institutes of Health, concludes that there is “consistent evidence” suggesting long-chain polyunsaturated fatty acids DHA and EPA are necessary for retinal health and may help protect the eyes from disease. (91)
A tremendous body of research has been conducted on these important nutrients since it was first discovered in the 1950s that fish oil offered many health benefits and that these benefits were attributable to a type of polyunsaturated fat called omega-3. Despite the volumes of research on omega-3s, it is only in recent years (within the last 15 years or so) that the actions of EPA and DHA have come to be understood individually. Researchers now often investigate the actions of EPA and DHA individually rather than together, no longer simply under the generic label omega-3 as they are widely referred to.
However, since the dosage of fish oil required for an ideal effect in the improvement of a patient is unknown, the Arthritis Center in the Department of Rheumatology at John Hopkins University considers including omega-3 fatty acids and fish oil in the treatment of arthritis as controversial. The University also cautions that arthritis patients must be wary of all the other side effects that can come from using fish oil. You can read more about arthritis on the web page of the Arthritis Foundation and the Arthritis Center.
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.
People should get most of their nutrients from food, advises the federal government's Dietary Guidelines for Americans. Foods contain vitamins, minerals, dietary fiber, and other substances that benefit health. In some cases, fortified foods and dietary supplements may provide nutrients that otherwise may be consumed in less-than-recommended amounts. For more information about building your own healthy eating pattern, visit ChooseMyPlate.gov. MyPlate offers messages, resources, and tools to help you make the choices that are right for you, based on the Dietary Guidelines for Americans.
To our knowledge, this is the first systematic review and meta-analysis to examine the anxiolytic effects of omega-3 PUFAs in individuals with anxiety symptoms. The overall findings revealed modest anxiolytic effects of omega-3 PUFAs in individuals with various neuropsychiatric or major physical illnesses. Although participants and diagnoses were heterogeneous, the main finding of this meta-analysis was that omega-3 PUFAs were associated with significant reduction in anxiety symptoms compared with controls; this effect persisted vs placebo controls. Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFA were significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions.

AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).


We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
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)
Various scales were used in these studies to evaluate the target outcome of anxiety symptoms: the Yale-Brown Obsessive-Compulsive Scale, Profile of Mood States, State-Trait Anxiety Inventory, Hamilton Anxiety Rating Scale, Generalized Anxiety Disorder questionnaire, Depression, Anxiety, and Stress Scales, Clinician-Administered Posttraumatic Stress Disorder Scale, Beck Anxiety Inventory, visual analog scale of anxiety, Impact of Event Scale–Revised, Conners score anxiety subscale, Neuropsychiatric Inventory, test anxiety severity, Hospital Anxiety and Depression Scale anxiety subscale, and Child Behavior Checklist anxiety subscale. The psychiatric and physical health conditions of the recruited participants also varied widely: general population without specific clinical conditions,36,47,51,55,60 participants with acute myocardial infarction,35 borderline personality disorder,2 mild to severe depression,59 obsessive-compulsive disorder,33 severe accidental injury,49 participants who were traumatized by disaster,54 participants with substance abuse disorder,34 women with premenstrual syndrome,56 children with attention-deficit/hyperactivity disorder,48,53 Alzheimer disease,58 generally healthy undergraduate college students but with test anxiety,61 Parkinson disease,52 and participants with Tourette syndrome.57 Sixteen studies compared the effect of omega-3 PUFA treatment with that of the placebo33,34,36,47-49,51-53,55-61; the other 3 studies were non–placebo controlled trials.35,50,54 The mean (SD) Jadad score of the recruited studies was 3.8 (1.0) (eTable in the Supplement).
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]
Your concerns are very valid. The quality of commercially available omega-3 preparations can vary greatly. In our clinical trials we use preparations made by reputable manufacturers with high standards. We also have the preparations analyzed by 2 independent labs to confirm omega-3 content, impurities, and degree of oxidation, prior to initiating the study. While omega-3 fatty acids–like most nutrients–are ideally obtained through dietary practice, because many people may not enjoy omega-3 containing foods, supplements may be a good option for these individuals. Anyone who is interested in using an omega-3 preparation for treating a psychiatric condition should do so preferably under the supervision of a psychiatrist.
Recently another Omega-3 fatty acid, DPA (Docosapentaenoic Acid) has been discussed more frequently in the scientific community, as a new and very potent Omega-3 fatty acid. Previously thought to work in through EPA and DHA we are now learning it has very distinct functions in the body. All three of these polyunsaturated fats play an important role in the functioning of our bodies.
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]
High triglycerides. Most research shows that fish oil from supplements and food sources can reduce triglyceride levels. The effects of fish oil appear to be the greatest in people who have very high triglyceride levels. Also the amount of fish oil consumed seems to directly affect how much triglyceride levels are reduced. Some fish oil supplements including Lovaza, Omtryg, and Epanova have been approved by the FDA to lower triglycerides.
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