Norris, J. M., Yin, X., Lamb, M. M., Barriga, K., Seifert, J., Hoffman, M., Orton, H. D., Baron, A. E., Clare-Salzler, M., Chase, H. P., Szabo, N. J., Erlich, H., Eisenbarth, G. S., and Rewers, M. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA 9-26-2007;298(12):1420-1428. View abstract.
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)

It seems that infancy and childhood are some of the most important periods of time in a person’s life to get plenty omega-3s in their diet, probably because of the amount of long-chain fatty acids found in the brain and retina. It’s crucial for developing babies and children to get a good amount of DHA and EPA so their brains and eyes develop fully and properly. (78)
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Dr. Holub has provided the questions and answers for several emails he has received over the years regarding omega-3 fatty acids for health.  If you have a question regarding omega-3, it is likely that Dr. Holub has answered it either here in this section, or elsewhere on the site (e.g. check the scientific overview section for general questions regarding omega-3).  To quickly find your answer, please use our search bar located in the top right section of this page.  After searching our site, and  you still cannot find the answer to your question, we invite you to ask Dr. Holub a question here.

Some research indicates that people who eat more seafood may have a reduced risk of cognitive decline. However, omega-3 supplements haven’t been shown to help prevent cognitive impairment or Alzheimer’s disease or to improve symptoms of these conditions. For example, a large NIH-sponsored study completed in 2015 indicated that taking EPA and DHA supplements did not slow cognitive decline in older adults. The people studied were participants in a larger eye disease study, and all of them had age-related macular degeneration (AMD). 
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.
Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
As always with such trials, you can never prove zero benefit (or zero risk), but an essentially negative trial or meta-analysis sets statistical limits on the size of any remaining plausible effect. What we can now say with a fairly high degree of confidence is that any health benefit from consuming omega-3 fatty acids is tiny, probably too small to warrant supplementing (or adding it to pasta).
Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaenoic acid (22:6, n-3; DHA).[67] These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges (-CH
While fish oil has plenty of beneficial qualities, there is a lot of hype around its possible applications, and not all of them are accurate, so be wary when reading literature on this useful oil. Fish oil manufacturers have attempted to market it as a remedy for almost anything. We suggest that readers educate themselves fully before making an informed decision, rather than getting affected by both negative and positive propaganda about the beneficial applications of fish oil.
Special attention should also be given to the fact that most women have major deficiencies of omega-3. A 1991 study at the Mayo Clinic focused on 19 "normal" pregnant women consuming "normal diets," and it showed that all were deficient in omega-3 fats. Another study compared Inuit (Eskimo) women to Canadian women, and it revealed omega-3 deficiency in the milk of the Canadian nursing moms.
The National High Blood Pressure Education Program in the United States has cautioned against inaccurate publicity of fish oil as an effective means of lowering high blood pressure in patients suffering from hypertension. According to its report, fish oil supplements lower blood pressure in a very small way in hypertensive patients. Research conducted at the Channing Laboratory in Boston has revealed that moderate doses of fish oil supplements have little effect on the condition of high blood pressure in normotensive people.
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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


A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]
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.
Some studies reported better psychomotor development at 30 months of age in infants whose mothers received fish oil supplements for the first four months of lactation.[45] In addition, five-year-old children whose mothers received modest algae based docosahexaenoic acid supplementation for the first 4 months of breastfeeding performed better on a test of sustained attention. This suggests that docosahexaenoic acid intake during early infancy confers long-term benefits on specific aspects of neurodevelopment.[45]
Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)

Finally, in order for AA to be converted into inflammatory products it must be released from phospholipids (part of the cell membrane) using the enzyme phospholipase A2 and then converted by the enzyme cyclooxygenase. EPA utilises both of these enzymes, so if EPA levels are increased in the diet, it attracts enzyme away from AA to EPA – again giving rise to anti-inflammatory products instead of inflammatory ones.
McNamara, R. K., Able, J., Jandacek, R., Rider, T., Tso, P., Eliassen, J. C., Alfieri, D., Weber, W., Jarvis, K., DelBello, M. P., Strakowski, S. M., and Adler, C. M. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr 2010;91(4):1060-1067. View abstract.
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.
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.
One day I was cooking pasta when the kitchen started to fill with the odor of fish. I happen to hate fish, so this was not a pleasant experience. It was also a mystery, since I never cook fish. A little detective work discovered that the offensive odor was coming from the pasta. Apparently I didn’t notice the “Now with Omega 3” label on the box when I purchased it. My daughter and I still refer to this as the “fish pasta incident”.
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. 
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.
Fish oil is very beneficial for pregnant women because the DHA present in it helps in the development of the eyes and brain of the baby. It also helps to avoid premature births, low birth weight, and miscarriages. Research conducted in Denmark, which involved 8,729 pregnant women, concluded that a diet with low amounts of fish resulted in a higher risk of premature or preterm babies.

Krauss-Etschmann, S., Hartl, D., Rzehak, P., Heinrich, J., Shadid, R., Del, Carmen Ramirez-Tortosa, Campoy, C., Pardillo, S., Schendel, D. J., Decsi, T., Demmelmair, H., and Koletzko, B. V. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J.Allergy Clin.Immunol. 2008;121(2):464-470. View abstract.

Some studies suggest that people who get higher amounts of omega-3s from foods and dietary supplements may have a lower risk of breast cancer and perhaps colorectal cancer. More research is needed to confirm this possible link. Whether omega-3s affect the risk of other cancers is not clear. Clinical trials to examine this possibility are in progress.
Meanwhile, blood levels of DHA and EPA are very transitory, reflecting what an individual consumed only recently, while of course prostate cancer has a markedly longer progression. The study was not designed to isolate omega oil :: prostate cancer relationships, so conclusion would be weak. Seems likely to me that when faced with a serious disease, men suddenly begin to try living “right” in a hurry.
Birch, E. E., Carlson, S. E., Hoffman, D. R., Fitzgerald-Gustafson, K. M., Fu, V. L., Drover, J. R., Castaneda, Y. S., Minns, L., Wheaton, D. K., Mundy, D., Marunycz, J., and Diersen-Schade, D. A. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 2010;91(4):848-859. View abstract.
It exists in nature in three forms, one derived from land plants and two derived from marine sources. In the body, omega-3 is highly concentrated in the brain; it is critical to the formation and maintenance of nerve cell membranes. Research shows that in the nervous system, omega-3s foster the development of brain circuitry and the processing of information. They also play important roles in stabilizing mood and staving off cognitive decline. Low levels of omega-3s are linked to poor memory and depression. Omega-3 fats are also critical for the formation of anti-inflammatory molecules in the body.
Jump up ^ Burch, Ernest S. (2006). Social Life in Northwest Alaska: The Structure of Iñupiaq Eskimo Nations. University of Alaska Press. p. 278. ISBN 9781889963921. Retrieved 2014-10-23. Oil was also used externally as an ointment to heal cold sores, cuts, insect bites, frostbite, rashes - in short, skin problems of all kinds. Duck or goose body-cavity fat was apparently as useful as seal or fish oil in dealing with skin problems.
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.
First difference is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme delta-6-desaturase (D6D) that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
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.
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.
Schilling, J., Vranjes, N., Fierz, W., Joller, H., Gyurech, D., Ludwig, E., Marathias, K., and Geroulanos, S. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12(6):423-429. View abstract.
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
The 'essential' fatty acids were given their name when researchers found that they are essential to normal growth in young children and animals. The omega−3 fatty acid DHA, also known as docosahexaenoic acid, is found in high abundance in the human brain.[70] It is produced by a desaturation process, but humans lack the desaturase enzyme, which acts to insert double bonds at the ω6 and ω3 position.[70] Therefore, the ω6 and ω3 polyunsaturated fatty acids cannot be synthesized and are appropriately called essential fatty acids.[70]
A lot of the benefit of fish oil seems to come from the omega-3 fatty acids that it contains. Interestingly, the body does not produce its own omega-3 fatty acids. Nor can the body make omega-3 fatty acids from omega-6 fatty acids, which are common in the Western diet. A lot of research has been done on EPA and DHA, two types of omega-3 acids that are often included in fish oil supplements.
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