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.

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.


Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).

The studies examining the possible benefits of omega-3s continue. Researchers are looking at a range of health outcomes and the impact of a heart healthy diet rich in omega 3 fatty acids on a range of chronic disease. For instance, Dr. Hooper's team is beginning to evaluate the effects that omega-3 fats may have on diabetes, dementia, and some cancers.
There is also evidence that mothers who use EPA and DHA supplementation during pregnancy and breastfeeding may protect their children against allergies. This may be due to the fact that fish-oil supplementation has been associated with decreased levels of body cells associated with inflammation and immune response (26). In a study about food allergy and IgE-associated eczema, the period prevalence of food allergy was lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05), and the incidence of IgE-associated eczema was also lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05) (27).
Dry eye. Some clinical research shows that eating more fish oil is linked to a lower risk of getting dry eye syndrome in women. Other research shows that taking a specific fish oil product (PRN Dry Eye Omega Benefits softgels) daily modestly improves symptoms of dry eye such as pain, blurred vision, and sensitivity. Other research using other forms of fish oil products suggests that taking these supplements for 4-12 weeks modest improves some dry eye symptoms. However, the sensation of eye dryness is not always improved. Other research also shows that taking a specific combination products containing fish oil and other ingredients might improve some dry eye symptoms; however, this research is conflicted and poor quality.
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.

A new Cochrane systematic review, published today in the Cochrane Library, combines the results of seventy-nine randomised trials involving 112,059 people. These studies assessed effects of consuming additional omega 3 fat, compared to usual or lower omega 3, on diseases of the heart and circulation. Twenty-five studies were assessed as highly trustworthy because they were well designed and conducted.
The number of presenters and the amount of information stuffed into an action-packed few days at times felt overwhelming, even for two dedicated omega-3 enthusiasts like us. But one important message did hit home: The omega-3 index could be a helpful indicator of various health risks, and we should all be paying closer attention to this measurement.
There was no significant association between the Hedges g and mean age (k, 17; P = .51), female proportion (k, 18; P = .32), mean omega-3 PUFA dosage (k, 19; P = .307), EPA to DHA ratio (k, 17; P = .86), dropout rate in the omega-3 PUFA group (k, 18; P = .71), duration of omega-3 PUFA treatment (k, 19; P = .14), Jadad score of randomization (k, 19; P = .10), Jadad score of blindness (k, 19; P = .57), or total Jadad score (k, 19; P = .18).
The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.[2] Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease.[4][5] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[6][7]
Excessive amounts of chemicals. Using excessive amounts of fish products such as shark, farm raised salmon or mackerel can be dangerous. These products may be exposed to excessive amounts of chemicals such as mercury which can build up in the body and cause negative effects. While it is healthy to consume fish, it is important to seek out quality sources to avoid exposure to these chemicals. Using a supplement to get high levels of omega-3s into your system is also recommended because these products are produced in such a way that they will not expose you to unsafe chemicals.
Matsumura  K, Noguchi  H, Nishi  D, Hamazaki  K, Hamazaki  T, Matsuoka  YJ.  Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: a randomized, double-blind, placebo-controlled trial.  J Affect Disord. 2017;224:27-31. doi:10.1016/j.jad.2016.05.054PubMedGoogle ScholarCrossref

If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.
Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.

Fatty predatory fish like sharks, swordfish, tilefish, and albacore tuna may be high in omega-3 fatty acids, but due to their position at the top of the food chain, these species may also accumulate toxic substances through biomagnification. For this reason, the United States Environmental Protection Agency recommends limiting consumption (especially for women of childbearing age) of certain (predatory) fish species (e.g. albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of the toxic contaminant mercury. Dioxin, PCBs and chlordane are also present.[13] Fish oil is used as a component in aquaculture feed. More than 50 percent of the world's fish oil used in aquaculture feed is fed to farmed salmon.[14]

In later life, cognitive function and brain deterioration may become a concern. Once again, maintaining high levels of EPA has been shown to lower the risk of developing and worsening cognitive decline and dementia. If, however, you know someone who already has a diagnosis of dementia or Alzheimer’s, their brain has already been damaged and needs structural support. At this point, DHA becomes important again and taking a high-EPA product that contains 250mg of DHA also is important to prevent further loss of brain tissue.
EPA and DHA  stand for eicosapentaenoic acid and docosahexaenoic acid respectively. These fatty acids are omega-3 fats, which are found in cold water fish. EPA DHA are highly unsaturated fats because they contain six and five double bonds on their long structural chains. These polyunsaturated fats play a very important role with the function of our bodies.
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.

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.
According to the American Heart Association (AHA), clinical trials have shown that omega-3 is effective in reducing the incidence of cardiovascular diseases (CVD). Fish oil is a great source of omega-3 and therefore, reduces the risk of heart diseases and heart arrhythmias. It also lowers the level of bad cholesterol (LDL) and increases the level of good cholesterol (HDL). Fish oil prevents the accumulation of triglycerides and also reduces the level of excess triglycerides. Preliminary research has shown that fish oil can be used to prevent atherosclerosis in coronary patients. Thus, fish oil is effective in preventing strokes and regular usage of fish oil can help avoid sudden cardiac death. As per the American Heart Association, these preliminary findings still need to be confirmed by a further detailed research.
Higdon JV, Liu J, Du S, et al. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)- isoprostanes. Am J Clin Nutr 2000;72:714-22. View abstract.
In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.
As mentioned above, the omega-3 index has been suggested as a predictor of the risk of coronary heart disease and other cardiovascular events. One study on a population in Seattle found that people with low omega-3 index levels were 10 times as likely to die from sudden cardiac death compared to people with higher omega-3 index levels (13). The NIH-funded Framingham study referenced above showed that the people with the highest omega-3 index levels had a 33% reduction in risk of death from any cause compared to the people with the lowest levels (2). In addition, a new study focused on individuals age 25 to 41 found that higher omega-3 index levels were associated with lower blood pressure in healthy adults (14).
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)
Jump up ^ Crowe, Francesca L.; Appleby, Paul N.; Travis, Ruth C.; Barnett, Matt; Brasky, Theodore M.; Bueno-de-Mesquita, H. Bas; Chajes, Veronique; Chavarro, Jorge E.; Chirlaque, Maria-Dolores (2014-09-01). "Circulating fatty acids and prostate cancer risk: individual participant meta-analysis of prospective studies". Journal of the National Cancer Institute. 106 (9): dju240. doi:10.1093/jnci/dju240. ISSN 1460-2105. PMC 4188122. PMID 25210201.
Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[61][62] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[63] It is under study as a candidate essential nutrient with roles in neurodevelopment, cognition, and neurodegenerative disorders.[61]

Heart disease. 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.
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