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.
ACS Breast Cancer Screening Guideline CDC Guideline for Prescribing Opioids CDC Guideline for Prevention of Surgical Site Infections Consensus Definitions for Sepsis and Septic Shock Global Burden of Cancer, 1990-2016 Global Burden of Disease in Children, 1990-2013 Global Burden of Hypertension, 1990-2015 Global Firearm Mortality, 1990-2016 Health Care Spending in the US and Other High-Income Countries Income and Life Expectancy in the US JNC 8 Guideline for Management of High Blood Pressure President Obama on US Health Care Reform Screening for Colorectal Cancer Screening for Depression in Adults Screening for Prostate Cancer Statins for Primary Prevention of Cardiovascular Disease The State of US Health, 1990-2016 US Burden of Cardiovascular Disease, 1990-2016 WMA Declaration of Helsinki, 7th Revision
RA causes chronic pain, swelling, stiffness, and loss of function in the joints. Some clinical trials have shown that taking omega-3 supplements may help manage RA when taken together with standard RA medications and other treatments. For example, people with RA who take omega-3 supplements may need less pain-relief medication, but it is not clear if the supplements reduce joint pain, swelling, or morning stiffness.

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]

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.


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.

Omega-3 fatty acids are frequently in the news regarding their health benefits (or doubts in some cases). Two types of omega-3s in particular - eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) – are known to be essential fatty acids. “Essential” refers to the fact that our cells need these fatty acids in order to function normally. But the body cannot make them from other fats, which means it’s “essential” we supply them in our diet or through supplementation.


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.

Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).
The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.

“Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine.” We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.
Most people get far too little omega-3s in their diet. In fact, research consistently indicates that the majority of Americans have just slightly more than half the amount of EPA and DHA in their tissues than they need for optimum brain and body health. This is partly due to a high dietary intake of unhealthy fats combined with an inadequate intake of EPA and DHA.
Copyright © 2018 Leaf Group Ltd. Use of this web site constitutes acceptance of the LIVESTRONG.COM Terms of Use, Privacy Policy and Copyright Policy. The material appearing on LIVESTRONG.COM is for educational use only. It should not be used as a substitute for professional medical advice, diagnosis or treatment. LIVESTRONG is a registered trademark of the LIVESTRONG Foundation. The LIVESTRONG Foundation and LIVESTRONG.COM do not endorse any of the products or services that are advertised on the web site. Moreover, we do not select every advertiser or advertisement that appears on the web site-many of the advertisements are served by third party advertising companies.
DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14
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.

Fish oil has the ability to treat Attention Deficit Hyperactivity Disorder (ADHD) due to its high concentration of fatty acids. For children suffering from hyperactivity, dyslexia, dyspraxia, inability to complete tasks, emotional instability, wavering attitude, poor coordination, short attention span, short-term memory weakness, low concentration, tendency to interrupt others, recklessness, hastiness, impetuosity, impulsiveness, low IQ, or learning disorders, fish oil is a proven remedy. Research conducted at the University of South Australia and CSIRO has shown that when children suffering from ADHD were given doses of fish oil and evening primrose capsules for 15 weeks, they showed significant improvements in their behavior. Since, human brain consists of about 60% fats, especially essential fatty acids such as omega-3 and omega-6, it helps to improve the functions of the brain.
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).
Keck, P. E., Jr., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., Frye, M. A., Altshuler, L. L., Kupka, R., Nolen, W. A., Leverich, G. S., Denicoff, K. D., Grunze, H., Duan, N., and Post, R. M. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol.Psychiatry 11-1-2006;60(9):1020-1022. View abstract.
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.
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.
There was a significantly greater association of treatment with reduced anxiety symptoms in participants receiving omega-3 PUFAs than in those not receiving omega-3 PUFAs in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g, 0.485; 95% CI, 0.017-0.954; P = .04; Figure 4)35,49,52,54-61 but no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the subgroup with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35) (Figure 4).33,34,36,47,48,50,51,53,60 There were no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .13).
Henneicke-von Zepelin, H. H., Mrowietz, U., Farber, L., Bruck-Borchers, K., Schober, C., Huber, J., Lutz, G., Kohnen, R., Christophers, E., and Welzel, D. Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. Br J Dermatol 1993;129(6):713-717. View abstract.
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).
Good points, Miroslav. Focusing on your 4th point, with so many different formulations on the market that contain various preservatives, only looking at the blood levels of omega-3’s as the flag for increased risk for prostate cancer tends to ignore the fact that certain populations in coastal regions maintain a diet high in omega fish oils and don’t have a marked increase level of prostate cancer, pointing to the fact that another agent may be to blame here.
Pay attention to the quality of fish oil when purchasing it. It is obtained from almost all fishes – fresh water, farm, ocean, deep sea and shallow sea fish. All these fishes can be contaminated with toxic compounds such as mercury, arsenic, lead, forms of calcium, furans, dioxins, PCBs, and methylmercury, and can negatively affect the human body. Therefore, the fish oil used must be pure. Many companies sell ultra refined or distilled fish oil, but you should always check if the standards have been followed and research on the company or the product before adding it to your diet.

Causing unsafe conditions. Fish oil may increase the risk of bleeding, which can lead to an unsafe condition. Excessive bleeding inside the body may also lead to conditions such as ulcers or liver disease which could be quite dangerous. Be aware of the signs and symptoms of this condition such as bruising easily or nosebleeds which could be a sign that you are developing this condition. If you begin to bleed more easily than usual then you should reduce the amount of fish oil you take regularly to reduce this condition.
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).
There have been conflicting results reported about EPA and DHA and their use with regard to major coronary events and their use after myocardial infarction. EPA+DHA has been associated with a reduced risk of recurrent coronary artery events and sudden cardiac death after an acute myocardial infarction (RR, 0.47; 95% CI: 0.219–0.995) and a reduction in heart failure events (adjusted HR: 0.92; 99% CI: 0.849–0.999) (34–36). A study using EPA supplementation in combination with a statin, compared with statin therapy alone, found that, after 5 y, the patients in the EPA group (n = 262) who had a history of coronary artery disease had a 19% relative reduction in major coronary events (P = 0.011). However, in patients with no history of coronary artery disease (n = 104), major coronary events were reduced by 18%, but this finding was not significant (37). This Japanese population already has a high relative intake of fish compared with other nations, and, thus, these data suggest that supplementation has cardiovascular benefits in those who already have sufficient baseline EPA+DHA levels. Another study compared patients with impaired glucose metabolism (n = 4565) with normoglycemic patients (n = 14,080). Impaired glucose metabolism patients had a significantly higher coronary artery disease HR (1.71 in the non-EPA group and 1.63 in the EPA group). The primary endpoint was any major coronary event including sudden cardiac death, myocardial infarction, and other nonfatal events. Treatment of impaired glucose metabolism patients with EPA showed a significantly lower major coronary event HR of 0.78 compared with the non–EPA-treated impaired glucose metabolism patients (95% CI: 0.60–0.998; P = 0.048), which demonstrates that EPA significantly suppresses major coronary events (38). When looking at the use of EPA+DHA and cardiovascular events after myocardial infarction, of 4837 patients, a major cardiovascular event occurred in 671 patients (13.9%) (39). A post hoc analysis of the data from these diabetic patients showed that rates of fatal coronary heart disease and arrhythmia-related events were lower among patients in the EPA+DHA group than among the placebo group (HR for fatal coronary heart disease: 0.51; 95% CI: 0.27–0.97; HR for arrhythmia-related events: 0.51; 95% CI: 0.24–1.11, not statistically significant) (39). Another study found that there was no significant difference in sudden cardiac death or total mortality between an EPA+DHA supplementation group and a control group in those patients treated after myocardial infarction (40). Although these last 2 studies appear to be negative in their results, it is possible that the more aggressive treatment with medications in these more recent studies could attribute to this.
For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research; Caruso’s Natural Health UltraMAX fish oil, Sydney, New South Wales, Australia) has been used once daily for 90 days.
×