Davidson, M. H., Stein, E. A., Bays, H. E., Maki, K. C., Doyle, R. T., Shalwitz, R. A., Ballantyne, C. M., and Ginsberg, H. N. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther 2007;29(7):1354-1367. View abstract.
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.
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
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
The Cochrane researchers found that increasing long-chain omega 3 provides little if any benefit on most outcomes that they looked at. They found high certainty evidence that long-chain omega 3 fats had little or no meaningful effect on the risk of death from any cause. The risk of death from any cause was 8.8% in people who had increased their intake of omega 3 fats, compared with 9% in people in the control groups.

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)


A 2008 meta-study by the Canadian Medical Association Journal found fish oil supplementation did not demonstrate any preventative benefit to cardiac patients with ventricular arrhythmias.[36] A 2012 meta-analysis published in the Journal of the American Medical Association, covering 20 studies and 68,680 patients, found that Omega-3 Fatty Acid supplementation did not reduce the chance of death, cardiac death, heart attack or stroke.[37]
One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[39] A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",[40] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[41] Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.[42]
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. [PubMed]

A number of trials have found that omega-3 PUFAs might reduce anxiety under serious stressful situations. Case-controlled studies have shown low peripheral omega-3 PUFA levels in patients with anxiety disorders.27-31 A cohort study found that high serum EPA levels were associated with protection against posttraumatic stress disorder.32 In studies of therapeutic interventions, while a randomized clinical trial of adjunctive EPA treatment in patients with obsessive-compulsive disorder revealed that EPA augmentation had no beneficial effect on symptoms of anxiety, depression, or obsessive-compulsiveness,33 a randomized clinical trial involving participants with substance abuse showed that EPA and DHA administration was accompanied by significant decreases in anger and anxiety scores compared with placebo.34 In addition, a randomized clinical trial found that omega-3 PUFAs had additional effects on decreasing depressive and anxiety symptoms in patients with acute myocardial infarction,35 and a randomized clinical trial demonstrated that omega-3 PUFAs could reduce inflammation and anxiety among healthy young adults facing a stressful major examination.36 Despite the largely positive findings of these trials, the clinical application of the findings is unfortunately limited by their small sample sizes.


A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."[42]
Your retina contains quite a bit of DHA, making it necessary for that fatty acid to function. (90) The National Eye Institute, part of the National Institutes of Health, concludes that there is “consistent evidence” suggesting long-chain polyunsaturated fatty acids DHA and EPA are necessary for retinal health and may help protect the eyes from disease. (91)
Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly inroe oil and green-lipped mussel and is only recently being recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead!
Jump up ^ Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales Jr, Marcelino L. Jr. (May–June 2013). "The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: a meta-analysis". Canadian Urological Association Journal. 7 (5–6): E333–43. doi:10.5489/cuaj.1056. PMC 3668400. PMID 23766835.

Fish oil can be consumed in various ways such as capsules or can be included in daily meals. The dosage should not exceed 3 fish oil capsules per day. 1000mg of fish oil contains approximately 300mg omega-3 fatty acids so you can accordingly use the amount of fish oil in your meals. A daily intake of 3000mg or less is safe for all. Pregnant and lactating women can consume approximately 3200 mg per day.
So why is an excess of DHA detrimental and an excess of EPA useful? DHA has a larger structure with two extra carbons and two extra double bonds, so it literally takes up more space in cell membranes than EPA. On the one hand, this is important because DHA plays a structural role in maintaining the fluidity of cell membranes ( essential for the normal function of proteins, channels and receptors that are also embedded in the membrane), but if a cell membrane becomes too saturated with DHA it can become too fluid, which can have a negative effect on cell function. EPA, on the other hand, is constantly utilised and always in demand.
Luo, J Rizkalla SW Vidal H Oppert JM Colas C Boussairi A Guerre-Millo M Chapuis AS Chevalier A Durand G Slama G. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. 1998;21(5):717-724. View abstract.

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.


Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 

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Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.

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.

In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
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.
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
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.
Warfarin (Coumadin) is used to slow blood clotting. Fish oil also might slow blood clotting. Taking fish oil with warfarin might slow blood clotting too much and increase the risk of bleeding. However, conflicting results suggests that fish oil does not increase the effects of warfarin. Until more is known, use cautiously in combination with warfarin. Have your blood checked regularly, as your dose of warfarin (Coumadin) might need to be changed.
In our analysis, most of the included studies showed a positive Hedges g toward a beneficial effect of omega-3 PUFAs in anxiety reduction, although not all findings were statistically significant. However, after merging of these effect sizes from all of the included studies, the main result showed significant findings in our meta-analysis. Despite the significant heterogeneity, no significant publication bias was found among these 19 studies.
Fish oil is also used for diabetes, prediabetes, asthma, a movement and coordination disorder called dyspraxia, dyslexia, eczema, autism, obesity, weak bones (osteoporosis), rheumatoid arthritis (RA), osteoarthritis, psoriasis, an autoimmune disease called systemic lupus erythematosus (SLE), multiple sclerosis, HIV/AIDS, cystic fibrosis, gum disease, Lyme disease, sickle cell disease, and preventing weight loss caused by some cancer drugs.
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