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.

CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.
Maternal nutrition guidelines have always stressed a diet including sufficient caloric and protein requirements, but recently fatty acids have also been deemed important (17). This is partially due to the fact that EPA and DHA supplementation during pregnancy has been associated with multiple benefits for the infant (Table 1). During pregnancy, the placenta transfers nutrients, including DHA, from the mother to the fetus (18). The amount of omega-3 fatty acid in the fetus is correlated with the amount ingested by the mother, so it is essential that the mother has adequate nutrition (19). The 2010 U.S. Department of Health and Human Services dietary guidelines recommend that women who are pregnant or breastfeeding should “consume 8 to 12 ounces of seafood per week from a variety of seafood types” (12). Ingesting 8–12 oz of seafood per week, depending on the type of fish, is equivalent to ∼300–900 mg EPA+DHA per day. Unfortunately, this amount is not being met by most mothers in the United States and Canada, which means that infants many not be receiving adequate amounts of these vital nutrients in the womb (20).
FDA pregnancy category C. It is not known whether Fish Oil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Fish Oil. It is not known whether omega-3 polyunsaturated fatty acids pass into breast milk or if this could harm a nursing baby. Do not use Fish Oil without telling your doctor if you are breast-feeding a baby. Do not give this medication to anyone under 18 years old.

Several small studies have shown that combination therapy with fish oil and HMG CoA reductase inhibitors is safe.56–61 The largest trial to date, the JELIS trial,32 was an open label trial of 18,645 Japanese adults with hypercholesterolemia who were randomized to a standard statin regimen or a fish oil formulation containing 1.8 g of EPA added to a statin medication. The cohort was made up mostly of postmenopausal, nonobese women with a 15% to 20% incidence of diabetes, tobacco use, or CAD. The primary outcome of any major cardiovascular event, at a mean of 4.6 years, was moderately reduced by a relative risk reduction of 26%. Both unstable angina and nonfatal MI were reduced, but no change was seen in sudden death. Overall, the findings were remarkable because at baseline approximately 90% of Japanese consumed at least 900 mg of EPA and DHA per day.62 The rates of cancer, joint pain, lumbar pain, or muscle pain were similar in the 2 groups. There was a similar rate of increase in measures of creatine phosphokinase, but more patients had an increase in aspartate aminotransferase levels (0.6% vs. 0.4%) in the fish oil group. The rate of bleeding was 1.1% in the fish oil combination group versus 0.6% in the HMG–CoA reductase inhibitor group.
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.
There are three types of omega-3 fatty acids, which include EPA, DHA and ALA, which is alpha-linoleic acid. Although EPA and DHA are found to have high amounts from animal sources, ALA is found in rich concentrations in plant sources, including certain vegetable oils and flaxseeds, although fatty fish and shellfish are the best sources of EPA and DHA, according to the National Center for Complementary and Alternative Medicine. Examples of these fatty fish and shellfish include salmon, tuna, trout, crab, oysters and mussels.
As with other supplements, when it comes to quality, you get what you pay for. Life Time sources its omega-3 fish oil (both capsules and liquid) from sustainable fisheries off the coast of Chile. We only use oils from small, cold-water anchovy, sardine, and mackerel. It’s molecularly distilled to be sure it’s free of mercury, PCBs, and heavy metals. If your fish oil brand doesn’t name the species of fish it’s sourced from, or it lists larger, predatory species, the quality and purity of the oil could be less than optimal.
Maclean, C. H., Mojica, W. A., Morton, S. C., Pencharz, J., Hasenfeld, Garland R., Tu, W., Newberry, S. J., Jungvig, L. K., Grossman, J., Khanna, P., Rhodes, S., and Shekelle, P. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid.Rep.Technol.Assess.(Summ.) 2004;(89):1-4. View abstract.
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

Due to the presence of Omega-3 fatty acids, fish oil has been promoted for relieving depression, sadness, anxiety, restlessness, mental fatigue, stress, decreased sexual desire, suicidal tendencies, and other nervous disorders. Researchers at the Case Western Reserve University School of Medicine in Cleveland, Ohio, in their research publication titled “Fish Oils and Bipolar Disorder: A Promising but Untested Treatment”, state that fish oil can be useful in mood stabilization and the treatment of bipolar disorders. It is unsurprising, therefore, that countries where fish is frequently eaten, have a low incidence of depression. Similarly, research conducted on prisoners has shown that when prisoners were given seafood containing a higher amount of omega-3 fatty acids, there was a significant drop in the homicide rate and the frequency of violence. Intake of fish is also a good remedy for depression. Findings of a research study suggest that fish consumption may be beneficial for women’s mental health and reduces the risk of developing depression in women.
Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).
Khandelwal, S., Demonty, I., Jeemon, P., Lakshmy, R., Mukherjee, R., Gupta, R., Snehi, U., Niveditha, D., Singh, Y., van der Knaap, H. C., Passi, S. J., Prabhakaran, D., and Reddy, K. S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br.J.Nutr. 2009;102(5):722-732. View abstract.
The chemical structures of EPA and DHA are very similar and they compete for uptake and processing resources. During digestion, the triglyceride molecules in standard fish oil are broken down into a mono glycerol and two free fatty acids, small enough to be absorbed into cells of the gut lining. More often than not, DHA is the fatty acid that remains attached to the glycerol backbone, meaning in essence that DHA gets a ‘free pass’ into the gut, while the remaining free fatty acids (more often EPA) must reattach onto a glycerol molecule or risk being oxidised and used as fuel. The implication of this is that DHA levels in our cells are often concentrated at the expense of EPA after absorption when taking EPA and DHA in the standard ratio of 1.5 to 1.

The nutritional value of seafood is important during early development. The Dietary Guidelines for Americans 2015–2020 and guidance from the U.S. Food and Drug Administration and Environmental Protection Agency recommend that women who are pregnant or breastfeeding eat at least 8 ounces but no more than 12 ounces of a variety of seafood each week, from choices that are lower in methyl mercury. Methyl mercury can be harmful to the brain and nervous system if a person is exposed to too much of it. 
^ Jump up to: a b Jensen, Craig L.; Voigt, Robert G.; Llorente, Antolin M.; Peters, Sarika U.; Prager, Thomas C.; Zou, Yali L.; Rozelle, Judith C.; Turcich, Marie R.; Fraley, J. Kennard; Anderson, Robert E.; Heird, William C. (2010). "Effects of Early Maternal Docosahexaenoic Acid Intake on Neuropsychological Status and Visual Acuity at Five Years of Age of Breast-Fed Term Infants". The Journal of Pediatrics. 157 (6): 900–05. doi:10.1016/j.jpeds.2010.06.006. PMID 20655543.
Grigg, L. E., Kay, T. W., Valentine, P. A., Larkins, R., Flower, D. J., Manolas, E. G., O'Dea, K., Sinclair, A. J., Hopper, J. L., and Hunt, D. Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty. J Am Coll Cardiol. 3-1-1989;13(3):665-672. View abstract.

Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3).[92] The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1,[93] soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3,[94] cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.[95]


If we want to deliver the benefits associated with EPA therapeutically, it is essential to optimise digestion and uptake. If we take EPA and DHA in their natural 1.5:1 ratio, it’s an uphill struggle for EPA because we know that DHA is more effectively absorbed and assimilated into cells. Delivering the benefits of EPA (for example, for cognitive function, mood and depression, inflammation regulation, heart health, skin health and so on), requires doses of EPA in excess of DHA, which determines the type of benefits obtained and the degree of the beneficial outcomes. The higher the ratio of EPA to DHA (meaning higher doses of EPA in relation to DHA), the more likely that EPA will be digested and absorbed, ready to meet the body’s high demands for this important nutrient.

Sorgi, P. J., Hallowell, E. M., Hutchins, H. L. & Sears, B. (2007, January 17). Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder. Nutrition Journal 6(16). Retrieved from http://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-16
Samsonov, M. A., Vasil'ev, A. V., Pogozheva, A. V., Pokrovskaia, G. R., Mal'tsev, G. I., Biiasheva, I. R., and Orlova, L. A. [The effect of a soy protein isolate and sources of polyunsaturated omega-3 fatty acids in an anti-atherosclerotic diet on the lipid spectrum of blood serum and immunological indicators in patients with ischemic heart disease and hypertension]. Vopr.Med Khim. 1992;38(5):47-50. View abstract.

Khandelwal, S., Demonty, I., Jeemon, P., Lakshmy, R., Mukherjee, R., Gupta, R., Snehi, U., Niveditha, D., Singh, Y., van der Knaap, H. C., Passi, S. J., Prabhakaran, D., and Reddy, K. S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br.J.Nutr. 2009;102(5):722-732. View abstract.


If you get your omega-3 index measured, you’ll know if your current efforts are sufficient. And this knowledge is especially important given that even health-conscious people are not always self-aware. One survey found that in a group of people with omega-3 index levels in the intermediate risk range, some 30% believed they were consuming enough omega-3s (11). One registered dietitian wrote a compelling story about exactly this experience. She discovered she was in the intermediate range, in spite of her intentions to eat enough fish.
What about blood clotting? Circulating cells called platelets are critical in causing your blood to clot. When platelets are activated, they aggregate and cause clots. If these clots occur in particularly sensitive regions of your body, they can lead to a heart attack or stroke. EPA reduces platelet activation, an early step in platelet aggregation to help to reduce clotting. One study found that EPA was superior to DHA in decreasing platelet activation, a precursor to blood clotting.1
After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.

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.
Finally, it is often assumed since there are not high levels of EPA in the brain, that it is not important for neurological function. Actually it is key for reducing neuro-inflammation by competing against AA for access to the same enzymes needed to produce inflammatory eicosanoids. However, once EPA enters into the brain it is rapidly oxidized (2,3). This is not the case with DHA (4). The only way to control cellular inflammation in the brain is to maintain high levels of EPA in the blood. This is why all the work on depression, ADHD, brain trauma, etc. have demonstrated EPA to be superior to DHA (5).
Abnormal rapid heart rhythms (ventricular arrhythmias). Population research suggests that eating a lot of fish has no effect on the risk for abnormal rapid heart rhythms. Clinical research is inconsistent. Some research shows that taking fish oil daily does not affect the risk for abnormal heart rhythms. But other research shows that taking fish oil for 11 months delays the development of the condition. However, overall, taking fish oil does not seem to reduce the risk of death in people with abnormal rapid heart rhythms.
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