The Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.
Dangour, A. D., Allen, E., Elbourne, D., Fasey, N., Fletcher, A. E., Hardy, P., Holder, G. E., Knight, R., Letley, L., Richards, M., and Uauy, R. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am.J.Clin.Nutr. 2010;91(6):1725-1732. View abstract.
Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[15] The various species range from lean to fatty and their oil content in the tissues has been shown to vary from 0.7% to 15.5%.[16] They also differ in their effects on organ lipids.[15] Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish, and serum omega−3 fatty acid concentrations.[17] Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA.[17]

Thusgaard, M., Christensen, J. H., Morn, B., Andersen, T. S., Vige, R., Arildsen, H., Schmidt, E. B., and Nielsen, H. Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study. Scand.J.Infect.Dis. 2009;41(10):760-766. View abstract.

Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
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.
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]
Hanwell, H. E., Kay, C. D., Lampe, J. W., Holub, B. J., and Duncan, A. M. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. J Nutr 2009;139(6):1128-1134. View abstract.

While fish for dinner is one way to get EPA and DHA, most people don’t eat the suggested two to three servings of oily fish per week to reap the benefits of omega-3s. What’s more, there are extremely few food sources, aside from fish, that naturally provide EPA and DHA. With all the benefits that can come from fish oil, it’s no surprise that these supplements are increasing in popularity.

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
The health benefits of fish oil include its ability to aid in weight loss and healthy pregnancy. It also promotes fertility and skin care (particularly for psoriasis and acne). It is beneficial in the treatment of various heart diseases, high cholesterol, depression, anxiety, ADHD, weak immune system, cancer, diabetes, inflammation, arthritis, IBD, AIDS, Alzheimer’s disease, eye disorders, macular degeneration, and ulcers.
All people need to consume omega-3 fats regularly. The recommended daily intake for adults is 1.6 grams for males  and 1.1 grams for females, according to the National Institutes of Health. The omega-3 family encompasses numerous fatty acids, but three primary forms are eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. The first two forms primarily occur in fish, such as salmon, mackerel, and tuna. The third can be found in plant oils, including flaxseed, soybean, walnut, and canola oils.
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]
Back in 2013, a study came out that made a lot of people concerned about fish oil supplements and cancer. The study, published in the Journal of the National Cancer Institute, showed that men who consume the largest amount of fish oil had a 71 percent higher risk of high-grade prostate cancer and a 43 percent increase in all types of prostate cancer. The study was conducted on 2,227 men, of which 38 percent of the men already had prostate cancer. (39)
Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
Several studies suggest that people suffering symptoms of depression and/or anxiety see improvement after adding an omega-3 supplement to their routine, even in double-blinded, randomized, controlled trials. (29, 30, 31, 32, 33) At least one study comparing a common depression medication found omega-3 supplements to be just as effective in combating depression symptoms. (34)

A Pregnancy Prerequisite: Omega-3 fatty acids directly affect brain development, making it crucial for expectant mothers. Additionally, research indicates they decrease a mother's risk of depression. When the mother doesn't have enough of these essential fatty acids, the baby borrows from her. Some prenatal vitamins now include omega-3s, so be sure to check the label or grab a handful of walnuts each day.

Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.

Omega-3 [(n-3)] fatty acids have been linked to healthy aging throughout life. Recently, fish-derived omega-3 fatty acids EPA and DHA have been associated with fetal development, cardiovascular function, and Alzheimer's disease. However, because our bodies do not efficiently produce some omega-3 fatty acids from marine sources, it is necessary to obtain adequate amounts through fish and fish-oil products. Studies have shown that EPA and DHA are important for proper fetal development, including neuronal, retinal, and immune function. EPA and DHA may affect many aspects of cardiovascular function including inflammation, peripheral artery disease, major coronary events, and anticoagulation. EPA and DHA have been linked to promising results in prevention, weight management, and cognitive function in those with very mild Alzheimer's disease.
Healthy cells require a delicate balance of EPA and DHA and the body employs clever mechanisms to support this natural equilibrium. DHA levels are self-regulated through inhibiting the activity of the enzyme delta-6 desaturase – the very enzyme that supports the conversion of EPA into DHA – to ensure levels of DHA do not become too high. It is therefore possible to have too much preformed DHA, if our supplement intake exceeds the body’s needs.

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]
Although results from studies regarding the disease processes of AD seem to be promising, there are conflicting data regarding the use of omega-3 fatty acids in terms of cognitive function. Neuropsychiatric symptoms accompany AD from early stages and tend to increase with the progression of the disease (55). An analysis of 174 patients randomized to a placebo group or to a group with mild to moderate AD (MMSE score ≥15) treated with daily DHA (1.7 g) and EPA (0.6 g) found that at 6 mo, the decline in cognitive function did not differ between the groups. Yet, in a subgroup with very mild cognitive dysfunction (n = 32, MMSE score >27), they observed a significant reduction in the MMSE decline rate in the DHA+EPA-supplemented group compared with the placebo group (47). Another study that looked at DHA supplementation in individuals with mild to moderate AD used the Alzheimer's Disease Assessment Scale–Cognitive subscale, which evaluates cognitive function on a 70-point scale in terms of memory, attention, language, orientation, and praxis. This study found that DHA supplementation had no beneficial effect on cognition during the 18-mo trial period for the DHA group vs. placebo (56).
The reason why fish oil could increase a man’s risk of prostate cancer is IMBALANCE. Like I said earlier, omega-6 fatty acids aren’t bad for you. In fact, if your diet contains too many omega-3 fatty acids, your immune system wouldn’t work very well because omega-3 and omega-6 fatty acids are meant to work in a system of checks and balances. Omega-3 fatty acids suppress inflammation, and omega-6 fatty acids promote inflammation, which actually supports your body’s natural system of defense like activating your white blood cells.
My initial interest in omga-3 was an article by Dr Andrew Stoll in Harvard about May 99, One of my bipolar patients had extreme OCD related to HIV which was not relevant to her. I put her on 9.6g of fish oil and continued her on her regular medication. She was well for the next 3 years with no obvious mental health problem when she was attending here.

The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).

Yamagishi, K., Iso, H., Date, C., Fukui, M., Wakai, K., Kikuchi, S., Inaba, Y., Tanabe, N., and Tamakoshi, A. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J.Am.Coll.Cardiol. 9-16-2008;52(12):988-996. 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.

The FDA product label on Lovaza warns of potential bleeding complications with the coadministration of anticoagulants. This warning is based on observational studies that suggested a prolonged bleeding time in populations ingesting high levels of fish oil77 and on in vitro studies that demonstrated an effect on pro-thrombotic mediators such as a reduction in thromboxane A2 production78 and platelet activation factor.79 The same trend, however, has not been clearly demonstrated in measurements of clotting times or in factors of fibrinolysis.80 In addition, in randomized clinical trials of patients undergoing coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, endarterectomy and diagnostic angiography, no adverse bleeding related events have been demonstrated.81 For example, in a trial of 500 patients randomized to pretreatment with 6.9 g of DHA and EPA preparation 2 weeks before balloon percutaneous transluminal coronary angioplasty (where all the patients received 325 mg/d of aspirin and heparin bolus periprocedure), no difference was seen in bleeding complications.82 Similar results were seen in a trial of 610 patients undergoing coronary artery bypass graft surgery, randomized to either placebo or 4 g/d of fish oil and then further randomized to aspirin or warfarin (dosed to an international normalized ratio [INR] goal of 2.5–4.2). At 1 year, the number of bleeding complications was not increased.15 The effect of fish oil on INR values has not been studied extensively, but a small, randomized trial showed that fish oil did not alter the Coumadin dosing regimen.83 There is very little evidence that a lower target INR is necessary in patients receiving chronic warfarin therapy and fish oil.

Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis. 


Arsenault, L. N., Matthan, N., Scott, T. M., Dallal, G., Lichtenstein, A. H., Folstein, M. F., Rosenberg, I., and Tucker, K. L. Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia. Am J Epidemiol 7-1-2009;170(1):95-103. View abstract.

The systematic review suggests that eating more ALA through food or supplements probably has little or no effect on cardiovascular deaths or deaths from any cause. However, eating more ALA probably reduces the risk of heart irregularities from 3.3 to 2.6%. The review team found that reductions in cardiovascular events with ALA were so small that about 1000 people would need to increase consumption of ALA for one of them to benefit. Similar results were found for cardiovascular death. They did not find enough data from the studies to be able to measure the risk of bleeding or blood clots from using ALA.
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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.
Mercury and polychlorinated biphenyls (PCBs) are common toxins in seafood. Although the U.S. banned the use of PCBs and DDT in 1976, these and other chemicals are still used in half the world's commercial chemical processes. Substances like these can hang around in the air, soil, and water for many years. They end up in the bodies of fish and animals.
Thank you for your kind comment. As pointed out above, the main limitation of our meta-analysis is the heterogeneity, which we address several times in our main manuscript. We included studies with several different situations and participants with different underlying diseases, which would also result in wide heterogeneity in our meta-analysis. Based upon our post-hoc analysis, there was some common characteristics among the six trials with nominally significant results, including specific clinical diagnoses (5/6) and, placebo-control (4/6), which had also previously been addressed in our subgroup meta-analysis. Therefore, we suggested future placebo-controlled trials investigating the treatment effect of omega-3 in participants with specific clinical diagnoses should be warranted. In addition, improving underlying specific clinical diagnoses (5/6), good quality (placebo-control (4/6), low drop-out rate (zero in Exp/control groups: 4/6)), and long treatment duration (>= 12 weeks: 4/6) are all good indicators of high quality.
In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bond (six in DHA vs. five in EPA) and increased carbon length (22 carbons in DHA vs. 20 in EPA) means that DHA takes up takes up a lot more space than does EPA in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than does EPA. This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye as it allows receptors to rotate more effectively thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these highly fluid portions of the nerves (7). On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.
Hernandez, D., Guerra, R., Milena, A., Torres, A., Garcia, S., Garcia, C., Abreu, P., Gonzalez, A., Gomez, M. A., Rufino, M., Gonzalez-Posada, J., Lorenzo, V., and Salido, E. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study. Nephrol.Dial.Transplant. 2002;17(5):897-904. View abstract.
Science is dynamic, not static, and as scientific understanding advances scientists sometimes have to modify their positions. Dr. Kidd’s position on EPA and DHA has now changed due to advances in the clinical and basic scientific research. Though the brain carries predominantly DHA and very little EPA, clinical trial results clearly indicate EPA has benefit for mood and probably other higher brain functions. At the basic science level, it has become clear that both EPA and DHA, not DHA alone, are required for the brain to make new nerve cells. Dr. Kidd very closely monitors the research on EPA and… Read more »
Preventing re-blockage of blood vessels after angioplasty, a procedure to open a closed blood vessel. Research suggests that fish oil decreases the rate of blood vessel re-blockage by up to 45% when given for at least 3 weeks before an angioplasty and continued for one month thereafter. But, when given for 2 weeks or less before angioplasty, it doesn't seem to have any effect.
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