A, Subgroup meta-analysis of the anxiolytic effect of omega-3 polyunsaturated fatty acids (PUFAs) based on an underlying specific clinical diagnosis or not. The anxiolytic effect of omega-3 PUFAs was not significant in the subgroup of participants without specific clinical conditions (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) but was significant in the subgroup of participants with specific clinical diagnoses (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01). Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFAs were significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03). B, Subgroup meta-analysis of the anxiolytic effect of omega-3 PUFAs based on different mean omega-3 PUFA dosages. The anxiolytic effect of omega-3 PUFAs was not significant in subgroups of mean omega-3 PUFA dosages less than 2000 mg/d (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) but was significant in the subgroup of mean omega-3 PUFA dosage of at least 2000 mg/d (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02).
DHA is especially vital for infant and child brain and nervous system development, as well as visual function. In older children, high DHA levels have been shown to improve learning ability, while deficiencies have been linked to learning problems and ADHD. And in adults, some studies have shown that DHA helps protect against cognitive decline and Alzheimer’s disease.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.


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)
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
Causing unsafe conditions. Fish oil may increase the risk of bleeding, which can lead to an unsafe condition. Excessive bleeding inside the body may also lead to conditions such as ulcers or liver disease which could be quite dangerous. Be aware of the signs and symptoms of this condition such as bruising easily or nosebleeds which could be a sign that you are developing this condition. If you begin to bleed more easily than usual then you should reduce the amount of fish oil you take regularly to reduce this condition.
“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.

ODS seeks to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, supporting research, sharing research results, and educating the public. Its resources include publications (such as Dietary Supplements: What You Need to Know), fact sheets on a variety of specific supplement ingredients and products (such as vitamin D and multivitamin/mineral supplements), and the PubMed Dietary Supplement Subset
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.
The various enzymes (COX and LOX) that make inflammatory eicosanoids can accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty in converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation whereas EPA can have a powerful impact.

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.
Fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[3][4][5][6] Earlier, in 2007, the American Heart Association had recommended the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautioned pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish.[32] (Optimal dosage was related to body weight.)
The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.

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


Currently, there isn’t a set standard recommendation for how many omega-3s we need each day, but suggestions range from a fish oil dosage of 500 to 1,000 milligrams daily depending on whom you ask. How easy is it to get these recommended amounts? To give you an idea, there are more than 500 milligrams of total omega-3s in one can of tuna fish and one small serving of wild-caught salmon.
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.
Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise, but this has not been supported by evidence in humans. (4) In the Health Professionals Follow-up Study, for example, the ratio of omega-6 to omega-3 fats wasn’t linked with risk of heart disease because both of these were beneficial. (5) Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats. Although there is no question that many Americans could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
Bergmann, R. L., Haschke-Becher, E., Klassen-Wigger, P., Bergmann, K. E., Richter, R., Dudenhausen, J. W., Grathwohl, D., and Haschke, F. Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Ann Nutr Metab 2008;52(2):157-166. View abstract.
Another recent study shows that fatty fish consumption can cut the risk of eye-diabetes complications. The researches tracked the seafood consumption of about 3,600 diabetic men and women between the ages of 55 and 80 for nearly five years. The researchers found that people who regularly consumed 500 milligrams each day of omega-3 fatty acid in their diets (equal to two servings of fatty fish per week) were 48 percent less likely to develop diabetic retinopathy than those who consumed less. (23)
To reap all the omega-3 benefits, it may be difficult for some people to eat the required amounts of oily fish, particularly with the well-known dangers of farmed fish, which are more readily available to most Americans. That’s why some people consider a high-quality omega-3 supplement in addition to a well-rounded diet. I’ll discuss supplements in a moment, though.

Omega-3s are generally safe and well tolerated. Stomach upset and “fishy taste” have been the most common complaints, but they are less frequent now thanks to manufacturing methods that reduce impurities. Past concerns about omega-3s increasing the risk of bleeding have been largely disproven, but caution is still advised in people taking blood thinners or who are about to undergo surgery. As mentioned, caution is needed in people with bipolar disorder to prevent cycling to mania. Because omega-3s are important to brain development, and pregnancy depletes omega-3 in expectant mothers, supplementation should theoretically benefit pregnant women and their children. Fish consumption in pregnancy is supported by the FDA, but because we do not have long-term data on safety or optimal dosing of omega-3s in pregnancy, expectant mothers should consider omega-3 supplements judiciously.
Added inactive ingredients also contribute to product safety. Eight supplements in this study contained ‘natural’ flavors such as citrus-derived additives. One product, Coromega Omega-3, also contained benzoic acid, a popular antibacterial agent linked to carcinogenic risks when combined with vitamin C. Other controversial excipients included the artificial coloring agents FD&C Blue 1 and FD&C Red 40 as well as the whitening agent titanium dioxide.
Evidence suggests that omega−3 fatty acids modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure.[25] Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation.[26][27] Omega−3 fatty acids reduce blood triglyceride levels but do not significantly change the level of LDL cholesterol or HDL cholesterol in the blood.[28][29] The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5-1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1-2 g/day; and >500 mg/dL be treated under a physician's supervision with 2-4 g/day using a prescription product.[30]
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.

Although there are no randomized data on fish oil consumption and protection from sudden death, observational studies have linked omega-3 FA with the prevention of sudden death. In a population-based, case-control study of sudden cardiac death victims, the mean red blood cell membrane omega-3 FA level of the lowest quartile, when compared with the mean level of the third quartile, was associated with a relative risk reduction of 70%.33 A similar finding was appreciated in a nested, prospective, case-control study of the Physician Health Study cohort of 22,000 healthy males. In the 119 patients that succumbed to sudden death, baseline omega-3 FA blood levels were significantly lower than in matched controls.34 Finally, in an analysis of data from the Nurses Health Study, a cohort study of 84,688 women, an inverse association was shown between fish consumption and CAD-related death. The investigators concluded that the reduction in CAD deaths was likely due to a reduction in sudden deaths, as there was no difference in the rate of MI when comparing high and low fish consumption.35
However, the researchers do have some good news. They concluded that omega 3 fatty acids do appear to reduce the type of blood cholesterol known as triglycerides, but that supplements probably are not useful for preventing or improving heart and circulatory problems. And, upping your intake of plant-based omega 3s high in ALA (ie, walnuts, flaxseed and flax oil, chia seeds) may help your heart somewhat.2
Capanni, M., Calella, F., Biagini, M. R., Genise, S., Raimondi, L., Bedogni, G., Svegliati-Baroni, G., Sofi, F., Milani, S., Abbate, R., Surrenti, C., and Casini, A. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment.Pharmacol.Ther. 4-15-2006;23(8):1143-1151. View abstract.
In recent years, many people – particularly those who strictly follow a vegetarian or vegan diet – have believed that they do not have to consume animal products to get omega-3s, as long as they are consuming high amounts of plant-based omega-3s. But, as I mentioned before, most of the health benefits that you can get from omega-3 fats are linked to animal-based EPA and DHA fats – not plant-based ALA. They are simply NOT interchangeable.
Kabir, M., Skurnik, G., Naour, N., Pechtner, V., Meugnier, E., Rome, S., Quignard-Boulange, A., Vidal, H., Slama, G., Clement, K., Guerre-Millo, M., and Rizkalla, S. W. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am.J.Clin.Nutr. 2007;86(6):1670-1679. View abstract.
Respected health care organizations proposed intake recommendations for oily fish of two servings per week for healthy adults, which equates to approximately a daily total of 500 milligrams (mg) EPA and DHA.‡ The recommendation encourages adults already with or at-risk of developing cardiovascular disease to talk to their primary healthcare professional about supplementing with amounts greater than 500 mg of EPA and DHA per day. Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.
The University of East Anglia (UEA) is a UK Top 15 university. Known for its world-leading research and outstanding student experience, it was awarded Gold in the Teaching Excellence Framework and  is a leading member of Norwich Research Park, one of Europe’s biggest concentrations of researchers in the fields of environment, health and plant science. www.uea.ac.uk.

Additional side effects of fish oil supplements which have been reported include headache, short-term memory loss, depression, somatic disorders, and increased risk of colon cancer, nasopharyngitis, worsening of asthma symptoms, hemolytic anemia, decreased physical activity, increased appetite, a general uncomfortable feeling or increased blood pressure. The percentage of users that develop these side effects is not known. If these side effects become severe it is recommended that you stop using fish oil supplements.
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.
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
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
To date, no studies have assessed mortality or nonfatal MI in diabetic patients treated with fish oil.52–54 A recent comprehensive meta-analysis analyzed the effect of fish oil supplements on metabolic parameters when added to usual care in patients with type 2 diabetes mellitus or impaired glucose tolerance.54 The meta-analysis included a total of 23 small, randomized trials with over 1000 patients that were assessed for lipid and insulin resistance parameters. At a mean follow-up of approximately 9 weeks, triglyceride reduction was accomplished but no significant changes were seen in total cholesterol, high-density lipoprotein-cholesterol, HgA1c levels, fasting glucose levels, fasting insulin, or in body weight. The largest randomized trial to date assessed approximately 400 patients with impaired glucose tolerance or insulin-dependent diabetes mel-litus, and as reflected in the larger meta-analysis, found no effect of moderate to high doses of fish oil on diabetic parameters.55 There are insufficient randomized data to comment on the combination of fish oil and specific diabetes medications and related mortality and/or morbidity.
Here is a brief on omega-3 fatty acids: There are three types of omega-3 fatty acids, namely alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). All three are important for the body. Vegetable sources, including flaxseed oil, soybean oil, hemp oil, canola oil, walnut oil, rapeseed, perilla, chia, and tofu are rich in ALA. The human body has the ability to convert ALA to DHA and EPA, though there are certain limitations to this conversion.

Weak bones (osteoporosis). Research suggests that taking fish oil alone or together with calcium and evening primrose oil slows the rate of bone loss and increases bone density at the thigh bone (femur) and spine in elderly people with osteoporosis. But taking fish oil does not slow bone loss in older people with osteoarthritis in the knee but without weak bones.

×