Irish AB, Viecelli AK, Hawley CM, et al; Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial. JAMA Intern Med. 2017;177(2):184-193. View abstract.
Fish oil is a concentrated source of omega-3 fats, which are also called ω-3 fatty acids or n-3 fatty acids. To get more scientific, omega-3s are long-chain polyunsaturated fatty acids, or PUFAs. Our bodies are able to make most of the fats we need need, but that’s not true for omega-3 fatty acids. When it comes to these essential fats, we need to get them from omega-3 foods or supplements.
Added inactive ingredients also contribute to product safety. Eight supplements in this study contained ‘natural’ flavors such as citrus-derived additives. One product, Coromega Omega-3, also contained benzoic acid, a popular antibacterial agent linked to carcinogenic risks when combined with vitamin C. Other controversial excipients included the artificial coloring agents FD&C Blue 1 and FD&C Red 40 as well as the whitening agent titanium dioxide.

Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]

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.
On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega−3 fatty acids, stating, "supportive but not conclusive research shows that consumption of EPA and DHA [omega−3] fatty acids may reduce the risk of coronary heart disease".[98] This updated and modified their health risk advice letter of 2001 (see below).
This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.
The two key omega-3 fatty acids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Fatty fish like salmon, mackerel, and sardines are rich in these omega-3s. Some plants are rich in another type of omega-3 fatty acid, alpha-linolenic acid, which the body can convert to DHA and EPA. Good sources of these are flaxseeds, chia seeds, walnuts, pumpkin seeds, and canola oil.
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.
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
The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
ALA is an essential fatty acid, which means that you need it but you must get this fat from your diet because your body is unable to produce it. In general, omega 3 fats are a crucial component of all cell membranes, including the eye (retina) and brain as well as aiding in the process of energy production to support functions involving the heart, lungs, immune system, and hormones (endocrine system), work properly.1

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 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.
The way that fish oil does that is to interfere with carbohydrate metabolism, and in insulin-resistant people or in people with specific genetic differences that might predispose them to having very high triglycerides, you do benefit from interfering that pathway with the fish oil, but I would actually try a low-carbohydrate diet in a lot of those situations to see if that helps with lowering triglycerides, or in the case of insulin resistance, I would try to address the insulin resistance at its root cause.
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).
Pumps the Heart: Where to begin? Omega-3s reduce triglycerides, stabilize your heartbeat, make platelets "less sticky" and can even lower blood pressure. The EPA you get with your daily DHA dose helps prevent artery-blocking clots. In the Iowa Nurses Study (and 3 others), 1 ounce of nuts a day decreased the incidence of heart disease between 20 and 60 percent.
Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the source of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass fed animals.[134] When cattle are taken off omega−3 fatty acid rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[135]

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 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.

Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.

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. 
The Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.

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.

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.

Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.

It’s no surprise that fish — particularly cold-water fatty fish like salmon, mackerel, and anchovies — are rich in omega-3s. It’s called fish oil for a reason, right? Mackerel, for instance, may have more than 3300 mg of omega-3 per serving — that’s more than 6 times the recommended per day dose for healthy adults. Not a huge fish connoisseur? Try some of the quick, simple recipes in Cooking with Fish Like a Pro, an accessible collection of fish recipes to suit every palate.
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]

In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
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).
Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
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.
While I think the article is good, it does not tell the reader that most of fish oil capsules sold over the counter are unregulated, and contain widely different ingredients and potency levels. They are mostly a waste of money. If you have health concerns, you need to consult an MD or a Registered Dietitian. Not a naturopath, homeopath, or other pseudoscience practitioner. Eat a diet rich in whole grains, nuts, and some oily fish. I take a multivitamin supplement made by CVS, formulated for my gender and age. Not from the food supplement shelves, which are unregulated, and might contain anything at all, or nothing but vegetable oil or cornstarch.
“This systematic review did find moderate evidence that ALA, found in plant oils (such as rapeseed or canola oil) and nuts (particularly walnuts) may be slightly protective of some diseases of the heart and circulation. However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia. One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.  ALA is an essential fatty acid, an important part of a balanced diet, and increasing intakes may be slightly beneficial for prevention or treatment of cardiovascular disease."
There is also evidence that mothers who use EPA and DHA supplementation during pregnancy and breastfeeding may protect their children against allergies. This may be due to the fact that fish-oil supplementation has been associated with decreased levels of body cells associated with inflammation and immune response (26). In a study about food allergy and IgE-associated eczema, the period prevalence of food allergy was lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05), and the incidence of IgE-associated eczema was also lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05) (27).
Children require DHA for growth and development, and the brain, CNS and retina rely heavily on the adequate supply of DHA during growth in the womb. Thus women should emphasise DHA in their diets when they become pregnant and continue to take this until they cease breastfeeding. Children continue to need DHA up until the age they start school, so if children under the age of five are taking an omega-3 supplement, it should contain DHA. The exception is for children with developmental problems – where pure EPA or high EPA omega-3 has been shown to be most effective for supporting cognitive function. We would still recommend, where possible, naturally derived sources of omega-3 such as oily fish to support a balanced EPA and DHA intake.

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.