There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
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.
Ramakrishnan, U., Stein, A. D., Parra-Cabrera, S., Wang, M., Imhoff-Kunsch, B., Juarez-Marquez, S., Rivera, J., and Martorell, R. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull 2010;31(2 Suppl):S108-S116. View abstract.
Age-related macular degeneration (AMD) is an eye disease that can cause vision loss in older people. Two major National Institutes of Health (NIH)-sponsored studies, called Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2), showed that dietary supplements containing specific combinations of vitamins, antioxidants, and zinc helped slow the progression of AMD in people who were at high risk of developing the advanced stage of this disease. AREDS2, which had more than 4,000 participants and was completed in 2013, also tested EPA and DHA. The results showed that adding these omega-3s to the supplement formulation didn’t provide any additional benefits. Other, smaller studies of omega-3 supplements also haven’t shown them to have a beneficial effect on the progression of AMD. 

In addition, there was 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 adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.

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.
Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms. In addition, participants receiving supplements containing less than 60% EPA showed a significant association, but not those receiving supplements containing 60% or more EPA. The depression literature supports the clinical benefits of EPA-enriched formulations (≥60% or ≥50%) compared with placebo for the treatment of clinical depression.9,13,73-75 This opposite effect of EPA-enriched formations on anxiety and depression is intriguing and possibly linked to a distinct underlying mechanism of omega-3 PUFAs. Exploration of the effects of omega-3 PUFAs on anxiety symptoms is just beginning and studies assessing the dose response anxiolytic effects of omega-3 PUFAs have not yet been performed. Further phase 2 trials of anxiety symptoms among participants with neuropsychiatric illness or physical illness should aim to determine the optimal dose.
Fish oil contamination even among “molecularly distilled” brands and those aimed at children is a widespread problem. One study in California tested 10 common brands and found PCBs — toxic industrial pollutants that have contaminated our oceans — in all of them. Some had 70 times the PCBs of other ones and 240x the toxicity. In another study, researchers tested 13 over-the-counter children’s dietary supplements containing fish oil for PCBs. PCBs were detected in all products. Our family takes algae-derived omega-3 (DHA/EPA) capsules, which are bioequivalent to fish oil capsules. Algae are actually the source where fish get their omega-3 content, so we skip the contaminated middle man (or, fish, in this case) and the neurotoxins that come with them given how polluted our oceans are now. I highly recommend parents do their research on what studies show about fish oil contamination and not just trust the labels, as well as consider algae-derived omega-3 capsules as more healthful bioequivalent to fish oil.
The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)
^ Jump up to: a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.

They also found that taking more long-chain omega 3 fats (including EPA and DHA), primarily through supplements probably makes little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities. Long-chain omega 3 fats probably did reduce some blood fats, triglycerides and HDL cholesterol. Reducing triglycerides is likely to be protective of heart diseases, but reducing HDL has the opposite effect. The researchers collected information on harms from the studies, but information on bleeding and blood clots was very limited. 

• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.

Gajos G1, Rostoff P, Undas A, et al. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010 Apr 20;55(16):1671-8. View abstract.

A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)
The benefits of omega-3 fatty acids (EPA and DHA), which are found in fish oil, have been supported by repeated double-blind clinical trials. In 2004, the FDA announced qualified health claims for omega-3 fatty acids, noting supportive but not conclusive research that shows that consuming EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. Our Fish Oil includes 200mg of omega-3 fatty acids from EPA and DHA.
Gorjao, R., Verlengia, R., Lima, T. M., Soriano, F. G., Boaventura, M. F., Kanunfre, C. C., Peres, C. M., Sampaio, S. C., Otton, R., Folador, A., Martins, E. F., Curi, T. C., Portiolli, E. P., Newsholme, P., and Curi, R. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006;25(6):923-938. View abstract.
Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[60][61] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[62]
Most vegan omega-3 supplements are made from seaweed, one of very few plant sources of both EPA and DHA. If you’d rather skip the pills, the real thing provides omega-3s as well as vitamin K, vitamin C, niacin, folate, and choline. Seaweed can be eaten raw (look for it at your local organic or Asian market) or dried — try Annie Chun’s Organic Seaweed Snack, which comes in individual packs and is available in several delicious flavors.

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.
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73

A healthy balance of dietary omega 6 and omega 3 fatty acids is a prerequisite for normal immune function, cognitive health, and cardiovascular health. Among other factors, sufficient dietary levels of EPA, DHA or other omega 3 fatty acids are also important in the regulation of normal blood lipoprotein and healthy cholesterol metabolism. Fish oil supplements can also lower elevated triglyceride levels, improving cardiovascular health and reducing the risk of heart disease.†

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
Jump up ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (July 2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition. 84 (1): 5–17. doi:10.1093/ajcn/84.1.5. PMID 16825676.
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.
Sala-Vila A, Díaz-López A, Valls-Pedret C, et al.; Prevención con Dieta Mediterránea (PREDIMED) Investigators. Dietary marine ?-3 fatty acids and incident sight-threatening retinopathy in middle-aged and older individuals with type 2 diabetes: Prospective investigation from the PREDIMED trial. JAMA Ophthalmol. 2016;134(10):1142-1149. View abstract.
Secondly, when we consume EPA, it inhibits the production of AA from DGLA and also competes with AA for uptake into cell membranes and can therefore lower the amount of AA in membranes by literally saturating the cell – in essence, it takes up more of the available ‘space’ and displaces AA. When there is less AA present, there is a reduced capacity for it to produce inflammatory products.
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]
In total, 19 articles with 19 data sets revealed the main results of the meta-analysis, namely that there was a significantly better association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 19; Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01; Figure 2), with significant heterogeneity (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) but no significant publication bias via Egger regression (t, 1.736; df, 17; P = .10) or inspection of the funnel plot (eFigure 2 in the Supplement). According to the trim-and-fill test, there was no need for adjustment for publication bias. The meta-analysis results remained significant after removal of any one of the included studies, which indicated that the significant results are not owing to any single study.
A certain kidney disease called IgA nephropathy. Some research shows that long-term but not short-term use of fish oil can slow the loss of kidney function in high-risk patients with IgA nephropathy. Fish oil might have greater effects when taken at higher doses. Also, it might be most effective in people with IgA nephropathy who have higher levels of protein in the urine.