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Oil derived from the tissues of oily fish
Omegaven

Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega 3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body and improve hypertriglyceridemia. There has been a great deal of controversy in the 21st century about the role of fish oil in cardiovascular disease, with recent meta analyses reaching different conclusions about its potential impact. The fish used as sources do not actually produce omega 3 fatty acids. Instead, the fish accumulate the acids by consuming either microalgae or prey fish that have accumulated omega 3 fatty acids. Fatty predatory fish like sharks, swordfish, tilefish, and albacore tuna may be high in omega 3 fatty acids, but due to their position at the top of the food chain, these species may also accumulate toxic substances through biomagnification. For this reason, the United States Environmental Protection Agency recommends limiting consumption (especially for women of childbearing age) of certain (predatory) fish species (e. g., albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of the toxic contaminant mercury. Dioxins, like PCBs and chlordane, as well as other chlorinated cyclodiene insecticides are also present. Fish oil is used in aquaculture feed, in particular for feeding farmed salmon. Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA. The various species range from lean to fatty, and their oil content in the tissues has been shown to vary from 0.7% to 15.5%. They also differ in their effects on organ lipids. Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA. None of these drugs are actually fish oil; they are all derivatives of acids found in fish oil.

The effect of fish oil consumption on prostate cancer is controversial. For instance, one study showed decreased risk with higher blood levels of DPA. However, another reported increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA. Some evidence indicated an association between high blood levels of omega 3 fatty acids and an increased prostate cancer risk. However, this evidence from the Select Trial has been challenged on the grounds of methodology and that the quantitative difference between those who developed prostate cancer and those who did not "is so small as to be biologically irrelevant".

There is uncertainty about the role of fish oil in cardiovascular disease, with reviews reaching different conclusions about its potential impact. Multiple evaluations suggest fish oil has little or no reduction on cardiovascular mortality, although there may be a small reduction in the incidence of actual cardiac events and strokes with its use. In 2007, the American Heart Association recommended the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautioned pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish. (Optimal dosage was related to body weight.) The US National Institutes of Health lists three conditions for which fish oil and other omega 3 sources are most highly recommended: hypertriglyceridemia (high triglyceride level), preventing secondary cardiovascular disease, and hypertension (high blood pressure). It then lists 27 other conditions for which there is less evidence. It also lists possible safety concerns: "Intake of 3 grams per day or greater of omega 3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil or omega 3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke." There were studies to determine if fish oil had an effect on certain abnormal heart rhythms, although a 2012 meta analysis found no significant effect. A 2008 meta study found fish oil supplementation did not demonstrate any preventative benefit to cardiac patients with ventricular arrhythmias. A 2012 meta analysis 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. A 2018 meta analysis of 77,000 participants found a 3% reduction in the relative risk for those who supplemented fish oil; however, this effect was deemed insignificant.

There have been some human trials that have concluded that consuming omega 3 fatty acids slightly reduces blood pressure (DHA could be more effective than EPA). Because omega 3 fatty acids can increase the risk of bleeding, a qualified healthcare provider should be consulted before supplementing with fish oil.

A 2008 Cochrane systematic review found that limited data is available. In the one eligible study, omega 3s were an effective adjunctive therapy for depressive but not manic symptoms in bipolar disorder. The authors found an "acute need" for more randomised controlled trials. 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. In a 2011 meta analysis of PubMed articles about fish oil and depression from 1965 to 2010, researchers found that "nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias." 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."

A 2019 meta analysis concluded that EPA ≥ 60% at a dosage of ≤1 g/d may have antidepressant effect.

A Cochrane meta analysis published in June 2012 found no significant protective effect for cognitive decline for those aged 60 and over and who started taking fatty acids after this age. A co author of the study said to Time, "Our analysis suggests that there is currently no evidence that omega 3 fatty acid supplements provide a benefit for memory or concentration in later life".

Some studies reported better psychomotor development at 30 months of age in infants whose mothers received fish oil supplements for the first four months of lactation. In addition, five year old children whose mothers received modest algae based docosahexaenoic acid supplementation for the first 4 months of breastfeeding performed better on a test of sustained attention. This suggests that docosahexaenoic acid intake during early infancy confers long term benefits on specific aspects of neurodevelopment.

A 2014 Cochrane review found that, based on two large studies, fish oil supplements did not appear to be effective for maintenance of remission in Crohn's disease.

Fish oil is a commonly used dietary supplement, with sales in the US alone reaching $976 million in 2009. By 2020 the global omega 3 supplement market size had reached $5.58 billion, and fish oil based supplements accounted for 63.1% of that market.

Fish oil supplements are available mainly as liquids or capsules. Most of these capsules are single piece gel capsules or softgels. Also available are enteric coated capsules that pass through the stomach before dissolving in the small intestine, thus helping prevent indigestion and "fish burps". Poorly manufactured enteric coated products have the potential to release ingredients too early. ConsumerLab. com, a for profit supplement testing company, reported that 1 of the 24 enteric coated fish oil supplements it evaluated released ingredients prematurely. and are usually present in fish oil gummies.

Generally, oily fish have more EPA than DHA versus salmon which has more DHA than EPA. To illustrate the amounts of EPA and DHA in supplements, a softgel capsule containing fish oil derived from pollock might contain a total of 642 mg of total fish oil, of which 584 mg are omega 3 fatty acids, with 377 mg EPA and 158 mg DHA.3 That same company's salmon oil softgel contains 1008 mg of total fish oil, of which 295 mg are omega 3 fatty acids, with 95 mg EPA and 118 mg DHA.4

According to ConsumerLab. com tests, the concentrations of EPA and DHA in supplements can vary from between 8 and 80% fish oil content. The concentration depends on the source of the omega 3s, how the oil is processed, and the amounts of other ingredients included in the supplement. A ConsumerLab. com publication in 2010 stated that 3 of 24 fish oil supplements tested contained less EPA and/or DHA than was claimed on the label.

A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury free". There appears to be little risk of contamination by microorganisms, proteins, lysophospholipids, cholesterol, and trans fats.

A 2013 review concluded that the potential for adverse events among older adults taking fish oil "appear mild–moderate at worst and are unlikely to be of clinical significance".

The FDA recommends that consumers do not exceed more than 3 grams per day of EPA and DHA combined, with no more than 2 grams from a dietary supplement. This is not the same as 3000 mg of fish oil. A 1000 mg pill typically has only 300 mg of omega 3; 10 such pills would equal 3000 mg of omega 3. According to the European Food Safety Authority's (EFSA) Panel on Dietetic Products, Nutrition and Allergies, supplementation of 5 grams of EPA and DHA combined does not pose a safety concern for adults. A 1987 study found that healthy Greenlandic Inuit had an average intake of 5.7 grams of omega 3 EPA per day which had many effects including prolonged bleeding times, such as slower blood clotting.

Two 2021 systematic reviews and meta analyses concluded that more than 1 g/d marine omega 3 fatty acids is associated with an increased risk of atrial fibrillation.

The liver and liver products (such as cod liver oil) of fish and many animals (such as seals and whales) contain omega 3, but also the active form of vitamin A. At high levels, this form of the vitamin can be dangerous (Hypervitaminosis A).