In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29
In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.
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).
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).
Like its other leafy green counterparts, broccoli is a powerful source of ALA, one of the omega-3 fatty acids your body needs (but can’t make on its own). Broccoli is also high in fiber, zinc, and — surprisingly — protein, a must for any ADHD brain. If you or your child doesn’t like broccoli, try pairing it with a cheesy sauce or baking it into tots — try this simple recipe to get started.
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.
Jump up ^ Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S (May 2011). "Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association". Circulation. 123 (20): 2292–333. doi:10.1161/CIR.0b013e3182160726. PMID 21502576.

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.

Hamazaki, K., Syafruddin, D., Tunru, I. S., Azwir, M. F., Asih, P. B., Sawazaki, S., and Hamazaki, T. The effects of docosahexaenoic acid-rich fish oil on behavior, school attendance rate and malaria infection in school children--a double-blind, randomized, placebo-controlled trial in Lampung, Indonesia. Asia Pac.J Clin Nutr 2008;17(2):258-263. View abstract.


Ozaydin, M., Erdogan, D., Tayyar, S., Uysal, B. A., Dogan, A., Icli, A., Ozkan, E., Varol, E., Turker, Y., and Arslan, A. N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study. Anadolu.Kardiyol.Derg. 2011;11(4):305-309. View abstract.
This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.

The results of several small studies had suggested that taking omega-3 supplements might help relieve symptoms of dry eye disease. However, a 2018 NIH-sponsored study that tested omega-3 supplements for a full year in a larger group (535 study participants) with moderate-to-severe dry eye disease found that the supplements were no more helpful than a placebo (an inactive substance).
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.
Bianconi, L., Calo, L., Mennuni, M., Santini, L., Morosetti, P., Azzolini, P., Barbato, G., Biscione, F., Romano, P., and Santini, M. n-3 polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study. Europace. 2011;13(2):174-181. View abstract.
Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula.

Protects Vision: Our eyes' retinas are a membranous structures and the whole eye is covered in a soft double layer of membranes, making your eyes' health dependent on the liver (who knew?). The liver helps metabolize fat-soluble vitamins that feed and maintain those membranes. If you're deficient in DHA, it affects how we see by delaying the system that converts light into neural energy in the retina.
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)

Katzman  MA, Bleau  P, Blier  P,  et al; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University.  Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders.  BMC Psychiatry. 2014;14(suppl 1):S1. doi:10.1186/1471-244X-14-S1-S1PubMedGoogle ScholarCrossref

To reach the required dose of EPA for treating certain conditions such as depression, CVD or CFS/ME you would need to take approximately 1-2 grams of ‘free EPA’ daily. Even with a concentrated omega-3 fish oil supplement, offering 180 mg excess EPA over DHA, this would require 10-20 capsules daily – significant in terms of volume and cost, and not efficient in terms of uptake in the body as our capacity for fat absorption is limited. The most effective and efficient way to ensure high EPA uptake in the body rapidly is to supplement with pure EPA for a minimum of 3-6 months.
What's more, ALA is just a precursor to EPA and DHA. You need certain enzymes to elongate and desaturate ALA so it can become long-chained omega-3s. Unfortunately, this does not work in some people, particularly those who are deficient in certain vitamins and minerals, leading to very low conversion rates – only 1 percent of ALA is converted to EPA/DHA. In some, the conversion can even dip as low as 0.1 to 0.5 percent!
Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.
This under-the-radar grain is a nutritional powerhouse — and one of the most potent sources of the omega-3 alpha-Linolenic acid (ALA). Sprinkle flaxseeds over your morning oatmeal for a pleasant nutty flavor, or blend them into fruit smoothies to satisfy a picky palate. Need more ideas? Check out The Flaxseed Recipe Book, an easy-to-follow guide for adding flaxseeds to your favorite soups, salads, and main courses.
The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.
Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
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.
Your concerns are very valid. The quality of commercially available omega-3 preparations can vary greatly. In our clinical trials we use preparations made by reputable manufacturers with high standards. We also have the preparations analyzed by 2 independent labs to confirm omega-3 content, impurities, and degree of oxidation, prior to initiating the study. While omega-3 fatty acids–like most nutrients–are ideally obtained through dietary practice, because many people may not enjoy omega-3 containing foods, supplements may be a good option for these individuals. Anyone who is interested in using an omega-3 preparation for treating a psychiatric condition should do so preferably under the supervision of a psychiatrist.
Ozaydin, M., Erdogan, D., Tayyar, S., Uysal, B. A., Dogan, A., Icli, A., Ozkan, E., Varol, E., Turker, Y., and Arslan, A. N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study. Anadolu.Kardiyol.Derg. 2011;11(4):305-309. View abstract.
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.
Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
One reason omega-3 fatty acids may be so beneficial to this many aspects of health could be that they help decrease system-wide inflammation. (49, 50, 51, 52, 53) Inflammation is at the root of most diseases and is related to the development of nearly every major illness, so by eating a nutrient-dense, anti-inflammatory diet, you give your body its best chance to fight disease like it was designed to do.
Both omega−6 and omega−3 fatty acids are essential: humans must consume them in their diet. Omega−6 and omega−3 eighteen-carbon polyunsaturated fatty acids compete for the same metabolic enzymes, thus the omega−6:omega−3 ratio of ingested fatty acids has significant influence on the ratio and rate of production of eicosanoids, a group of hormones intimately involved in the body's inflammatory and homeostatic processes, which include the prostaglandins, leukotrienes, and thromboxanes, among others. Altering this ratio can change the body's metabolic and inflammatory state.[16] In general, grass-fed animals accumulate more omega−3 than do grain-fed animals, which accumulate relatively more omega−6.[86] Metabolites of omega−6 are more inflammatory (esp. arachidonic acid) than those of omega−3. This necessitates that omega−6 and omega−3 be consumed in a balanced proportion; healthy ratios of omega−6:omega−3, according to some authors, range from 1:1 to 1:4.[87] Other authors believe that a ratio of 4:1 (4 times as much omega−6 as omega−3) is already healthy.[88][89] Studies suggest the evolutionary human diet, rich in game animals, seafood, and other sources of omega−3, may have provided such a ratio.[90][91]
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
This under-the-radar grain is a nutritional powerhouse — and one of the most potent sources of the omega-3 alpha-Linolenic acid (ALA). Sprinkle flaxseeds over your morning oatmeal for a pleasant nutty flavor, or blend them into fruit smoothies to satisfy a picky palate. Need more ideas? Check out The Flaxseed Recipe Book, an easy-to-follow guide for adding flaxseeds to your favorite soups, salads, and main courses.
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
For several years now, the fish oil and Alzheimer’s disease connection has been studied with consistent results. The essential fatty acids vital for brain function that are found in fish oil can not only slow cognitive decline, but can help prevent brain atrophy in older adults. A study published in the FASEB Journal looked at the health effects of four- to 17-month dietary supplementation with omega-3 fatty acids and antioxidants. The findings once again confirm the potential for fish oil to be used as a weapon to fend off the onset of cognitive decline and Alzheimer’s disease. (8)
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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