Fish oil



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 have other health benefits.

Fish do not actually produce omega-3 fatty acids, but instead accumulate them by consuming either microalgae or prey fish that have accumulated omega-3 fatty acids, together with a high quantity of antioxidants such as iodide and selenium, from microalgae, where these antioxidants are able to protect the fragile polyunsaturated lipids from peroxidation.

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 U.S. Food and Drug Administration recommends limiting consumption of certain (predatory) fish species (e.g. albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of toxic contaminants such as mercury, dioxin, PCBs and chlordane. Fish oil is used as a component in aquaculture feed. More than 50 percent of the world's fish oil used in aquaculture feed is fed to 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 0.7–15.5%. They also differ in their effects on organ lipids. Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish and serum omega−3 fatty acid concentrations. 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.

The omega-3 fatty acids in fish oil are thought to be beneficial in treating hypertriglyceridemia, and possibly beneficial in preventing heart disease. Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression, anxiety, cancer, and macular degeneration, although benefit in these conditions remains to be proven.

Background
The most widely available dietary source of EPA and DHA is cold water oily fish, such as salmon, herring, mackerel, anchovies, and sardines. Oils from these fish have a profile of around seven times as much omega-3 oils as omega-6 oils. Other oily fish, such as tuna, also contain omega-3 in somewhat lesser amounts. Although fish is a dietary source of omega-3, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.

For comparison, here are the omega-3 levels in some common non-fish foods.

Production
In 2005, fish oil production declined in all main producing countries with the exception of Iceland. The 2005 production estimate is about 570,000 tonnes in the five main exporting countries (Peru, Denmark, Chile, Iceland and Norway), a 12% decline from the 650,000 tonnes produced in 2004. Peru continues to be the main fish oil producer worldwide, with about one fourth of total fish oil production.

Cancer
Several studies report possible anti-cancer effects of n−3 fatty acids found in fish oil (particularly breast, colon and prostate cancer). Among n-3 fatty acids (omega-3), neither long-chain nor short-chain forms were consistently associated with reduced breast cancer risk. High levels of docosahexaenoic acid, however, the most abundant n-3 polyunsaturated fatty acid (omega-3) in erythrocyte membranes, were associated with a reduced risk of breast cancer. A recent study of 35,000 middle-aged women found that the women who took fish oil supplements had a 32% lower risk of breast cancer, although the authors stress the result is preliminary and falls short of establishing a causal relationship. Omega-3 fatty acids reduced prostate cancer growth, slowed histopathological progression, and increased survival in genetically engineered mice. However the effects of fish oil consumption by humans on prostate cancer is not conclusive. There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA.

Cardiovascular
The American Heart Association recommends the consumption of 1g of fish oil daily, preferably by eating fish, for patients with coronary heart disease although pregnant and nursing women are advised to avoid eating fish with high potential for mercury contaminants including mackerel, shark, or swordfish. Note that optimal dosage relates 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, secondary cardiovascular disease prevention and 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/omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke."

There is also some evidence that fish oil may have a beneficial effect on some forms of cardiac dysrhythmia.

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. A 2012 meta-analysis published in the Journal of the American Medical Association, covering 20 studies and 68680 patients, found that Omega-3 Fatty Acid supplementation did not reduce the chance of death, cardiac death, heart attack or stroke.

Hypertension
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). It is important to note that because omega-3 fatty acids can increase the risk of bleeding, a qualified healthcare provider should be consulted before supplementing with fish oil.

Mental health
Studies published in 2004 and 2009 have suggested that the n-3 EPA may reduce the risk of depression and suicide. One study compared blood samples of 100 suicide-attempt patients to those of controls and found that levels of Eicosapentaenoic acid were significantly lower in the washed red blood cells of the suicide-attempt patients. A small American trial in 2009 suggested that E-EPA, as monotherapy, might treat major depressive disorder but failed to achieve statistical significance.

Studies were conducted on prisoners in England where the inmates were fed seafood which contains omega-3 fatty acids. The higher consumption of these fatty acids corresponded with a drop in the assault rates. Another Finnish study found that prisoners who were convicted of violence had lower levels of omega–3 fatty acids than prisoners convicted of nonviolent offenses. It was suggested that these kinds of fatty acids are responsible for the neuronal growth of the frontal cortex of the brain which, it is further alleged, is the seat of personal behavior.

A study from the Orygen Research Centre in Melbourne suggests that omega-3 fatty acids could also help delay or prevent the onset of schizophrenia. The researchers enlisted 81 'high risk' young people aged 13 to 24 who had previously suffered brief hallucinations or delusions and gave half of them capsules of fish oil while the other half received placebo. One year on, only three percent of those on fish oil had developed schizophrenia compared to 28 percent from those on placebo. A study conducted at Sheffield University in England reported positive results with fish oil on patients suffering from schizophrenia. Participants of the study had previously taken anti-psychotic prescription drugs that were no longer effective. After taking fish oil supplements, participants in the study experienced progress compared to others who were given a placebo.

The largest controlled study to date found no cognitive benefit after two years in the elderly.

Evidence regarding the efficacy of fish oil supplements as a treatment for depression is inconclusive. Whereas several methodologically rigorous studies have reported statistically significant positive effects in the treatment of depressed patients, other studies have found effects to be insignificant.

In 1999 a team of researchers lead by the Harvard psychiatrist Andrew Stoll published a preliminary placebo-controlled double blind trial which found Omega 3 fatty acids "improved the short-term course of illness" of bipolar disorder. He credits Donald O. Rudin for pioneering this view in 1981.

A 2003 double-blind placebo-controlled study published in the journal European Neuropsychopharmacology found that among 28 patients with major depressive disorder, "patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group." Another study in the American Journal of Psychiatry reported that the addition of fish oil supplements to regular maintenance anti-depression therapy conferred "highly significant" benefits by the third week of the trial.

A 2005 randomized double-blind placebo-controlled study conducted under the auspices of the New Zealand Institute for Crop and Food Research found "no evidence that fish oil improved mood when compared to placebo, despite an increase in circulating ω-3 polyunsaturated fatty acids." Another study published in October 2007 found that fish oil supplements conferred no additional benefits beyond those conferred by standard treatment. However, both of these studies used omega-3 primary consisting of DHA, not EPA.

A 2008 Cochrane systematic review found that limited data is available. In the one eligible study, omega-3s were an effective adjunctive therapy for depressed 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 less 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 1965-2010, researchers found that "nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias."

Alzheimer's disease
According to a study from Louisiana State University in September 2005, Docosahexaenoic acid, an omega-3 fatty acid often found in fish oil, may help protect the brain from cognitive problems associated with Alzheimer's disease.

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".

Lupus
In a study conducted in Northern Ireland, lupus disease activity, especially in the skin and joints, was significantly reduced in patients who received fish oil supplements at both 12-week and 24-week follow-up periods versus patients who received placebo. There were also changes in the blood platelets of the patients who took the fish oil supplements, with an increase in proteins that are considered anti-inflammatory and a decrease in proteins that promote inflammation; these changes were not evident in the group that took placebo. The fish oil group showed an increase in flow-mediated dilation, which the researchers took as a sign that the omega-3 oils were helping the cells in the blood vessel walls to remain healthy.

Parkinson's disease
A study examining whether omega-3 exerts neuroprotective action in Parkinson's disease found that it did exhibit a protective effect in mice. The scientists exposed mice to either a control or a high omega-3 diet from two to twelve months of age and then treated them with a neurotoxin commonly used as an experimental model for Parkinson's. The scientists found that high doses of omega-3 given to the experimental group prevented the neurotoxin-induced decrease of dopamine that ordinarily occurs. Since Parkinson's is a disease caused by disruption of the dopamine system, this protective effect exhibited could show promise for future research in the prevention of Parkinson's disease.

Psoriasis
Diets supplemented with cod liver oil have shown beneficial effects on psoriasis.

Pregnancy
Omega-3 polyunsaturated fatty acids (commonly found in fish oil) protect against fetal brain injury and promotes fetal and infant brain health. Some studies reported better psycho motor 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.

Docosahexaenoic acid supplementation has also been found to be essential for early visual development of the baby. However, the standard western diet is severely deficient in these critical nutrients. This omega-3 dietary deficiency, a nutrient found in fish oil, is compounded by the fact that pregnant women become depleted in omega-3s, since the fetus uses omega-3s for its nervous system development. Omega-3s are also used after birth if they are provided in breast milk.

In addition, provision of fish oil during pregnancy may reduce an infant’s sensitization to common food allergens and reduce the prevalence and severity of certain skin diseases in the first year of life. This effect may persist until adolescence with a reduction in prevalence and/or severity of eczema, hay fever and asthma.

Omega-3 fatty acid supplementation is also beneficial to the mother. It has been shown to prevent pre-term labor and delivery. It is recommended that women who are breastfeeding consume fish oil at least twice a week, although the American Heart Association recommends pregnant and nursing women are to avoiding eating fish with high potential for mercury contaminants including mackerel, shark, or swordfish.

Supplement quality and concerns
Fish oil is now one of the most popular dietary supplements on the market, with sales reaching $976 million in 2009. However, neither the FDA nor any other federal or state agency routinely tests fish or marine oil supplements for quality prior to sale. Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems include contamination, inaccurate listing of EPA and DHA levels, spoilage and formulation issues.

Contamination
Fish can accumulate toxins such as mercury, dioxins, and polychlorinated biphenyls (PCBs), and spoiled fish oil may produce peroxides. There appears to be little risk of contamination by microorganisms, proteins, lysophospholipids, cholesterol, and trans-fats.

Mercury
While a serving of fish may contain anywhere from 10 to 1,000 ppb of mercury, fish oil supplements have not been found to contain similar mercury levels. Reasons for this are 1) smaller fish are typically used in making fish oil supplements and they tend to be lower on the food chain and contain less mercury; 2) mercury binds to protein (such as in fish meat) and not to oil; and 3) mercury may be reduced or removed during the processing of fish oil. (most fish oils are distilled)

Dioxins and PCBs
Dioxins and PCBs may be carcinogenic at low levels of exposure over time. These substances are identified and measured in one of two categories, dioxin-like PCBs and total PCBs. While the U.S. FDA has not set a limit for PCBs in supplements, the Global Organization for EPA and DHA (GOED) has established a guideline allowing for no more than 3 picograms of dioxin-like PCBs per gram of fish oil. In 2012, samples from 35 fish oil supplements were tested for PCBs. Trace amounts of PCBs were found in all samples, and two samples exceeded the GOED‘s limit. Although trace amounts of PCBs contribute to overall PCB exposure, Consumerlab.com claims the amounts reported by tests it ordered on fish oil supplements are far below those found in a single typical serving of fish.

Spoilage
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. ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.

EPA and DHA content
Some countries recommend a combined daily intake of 300 – 500 mg while some countries like the US do not have a recommendation for EPA and DHA. The American Heart Association recommends 250–500 mg/day of EPA and DHA. In the United States the FDA recommends not exceeding 3 grams per day of EPA and DHA omega-3 fatty acids, with no more than 2 grams per day from a dietary supplement.

According to independent laboratory tests, the concentrations of EPA and DHA in supplements can vary from between 8 to 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 2012 report claims 4 of 35 fish oil supplements it covered contained less EPA or DHA than was claimed on the label, and 3 of 35 contained more A ConsumberLab.com publication in 2010 claims 3 of 24 fish oil supplements it covered contained less EPA and/or DHA than was claimed on the label.

Formulation
Fish oil supplements are available as liquids, capsules, and tablets. Some pills are enteric-coated to help prevent indigestion or "fish burps", however; enteric-coated products have the potential to release ingredients too early or late in the digestive process. In 2010 ConsumerLab.com reports that one of 24 fish oil supplements with enteric-coated pill released ingredients prematurely ; Consumerlab.com claims in its publication that there were problems in results of tests it ordered in 2012. Fish oils are best tolerated when taken with meals, and, if possible, should be taken in equally divided doses throughout the day.

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

Maximum intake
The FDA says it is safe to take up to 3000 mg of omega-3 per day. (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.) Dyerberg studied healthy Greenland Eskimos and found an average intake of 5700 mg of omega-3 EPA per day.

Vitamins
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).

Toxic pollutants
Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.

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, 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.

A March 2010 lawsuit filed by a California environmental group claimed that eight brands of fish oil supplements contained excessive levels of PCB's, including CVS/pharmacy, Nature Made, Rite Aid, GNC, Solgar, Twinlab, Now Health, Omega Protein and Pharmavite. The majority of these products were either cod liver or shark liver oils. Those participating in the lawsuit claim that because the liver is the major filtering and detoxifying organ, PCB content may be higher in liver-based oils than in fish oil produced from the processing of whole fish.

An analysis based on data from the Norwegian Women and Cancer Study (NOWAC) with regards to the dangers of persistent organic pollutants (POPs) in cod liver came to the conclusion that "in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found."

However, 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." Microalgae oil is a vegetarian alternative to fish oil. Supplements produced from microalgae oil provide a balance of omega-3 fatty acids similar to fish oil, with a lower risk of pollutant exposure.