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[[Image:Fish oil softgel.jpg|thumb|100px|right|A typical fish oil [[softgel]]]]
[[Image:Fish oil softgel.jpg|thumb|100px|right|A typical fish oil [[softgel]]]]


'''Fish oil''' is [[oil]] derived from the [[biological tissue|tissues]] of [[oily fish]]. Fish oils contain the [[omega-3 fatty acid]]s [[eicosapentaenoic acid]] (EPA) and [[docosahexaenoic acid]] (DHA), precursors of certain [[eicosanoid]]s that are known to reduce [[inflammation]] in the body,<ref>{{cite journal |pages=402–10 |doi=10.1080/10408390701424303 |title=Advances in Dietary Enrichment with N-3 Fatty Acids |year=2008 |last1=Moghadasian |first1=Mohammed H. |journal=Critical Reviews in Food Science and Nutrition |volume=48 |issue=5 |pmid=18464030}}</ref><ref>{{cite journal |pages=679–81 |doi=10.1186/ar1876 |year=2006 |last1=Cleland |first1=Leslieg |last2=James |first2=Michaelj |last3=Proudman |first3=Susannam |journal=Arthritis Research & Therapy |volume=8 |pmid=16542466 |pmc=1526555 |title=Fish oil: What the prescriber needs to know |issue=1}}</ref> and have other health benefits.
'''Fish oil''' is [[oil]] derived from the [[biological tissue|tissues]] of [[oily fish]]. Fish oils contain the [[omega-3 fatty acid]]s [[eicosapentaenoic acid]] (EPA) and [[docosahexaenoic acid]] (DHA), precursors of certain [[eicosanoid]]s that are known to reduce [[inflammation]] in the body,<ref>{{cite journal |pages=402–10 |doi=10.1080/10408390701424303 |title=Advances in Dietary Enrichment with N-3 Fatty Acids |year=2008 |last1=Moghadasian |first1=Mohammed H. |journal=Critical Reviews in Food Science and Nutrition |volume=48 |issue=5 |pmid=18464030}}</ref><ref>{{cite journal |pages=679–81 |doi=10.1186/ar1876 |year=2006 |last1=Cleland |first1=Leslieg |last2=James |first2=Michaelj |last3=Proudman |first3=Susannam |journal=Arthritis Research & Therapy |volume=8 |pmid=16542466 |pmc=1526555 |title=Fish oil: What the prescriber needs to know |issue=1}}</ref> and have other health benefits. Fish oils also contain docosapentaenoic acid (DPA), an intermediary of EPA and DHA that studies suggest contributes to cardiovascular, cognitive, and neurological health. <ref> [http://www.naturalproductsinsider.com/articles/2011/08/dpa-on-the-rise.aspx Byelashov, Alex. “DPA on the Rise.” Natural Products Insider. 2011.] </ref>


The fish used as sources 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 acid]]s, together with a high quantity of [[antioxidant]]s such as [[iodide]] and [[selenium]], from microalgae, where these antioxidants are able to protect the fragile polyunsaturated lipids from [[Lipid peroxidation|peroxidation]].<ref name="venturi">{{cite journal |author=Venturi S, Donati FM, Venturi A, Venturi M |title=Environmental iodine deficiency: A challenge to the evolution of terrestrial life? |journal=Thyroid |volume=10 |issue=8 |pages=727–9 |year=2000|pmid=11014322 |doi=10.1089/10507250050137851}}</ref><ref name="venturi2">{{cite journal |author=Venturi S, Venturi M |title=Evolution of Dietary Antioxidant Defences |year=2007 |journal=European Epi-Marker |volume=11 |issue=3 |pages=1–12}}</ref><ref>{{cite journal |doi=10.1073/pnas.0709959105 |title=Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry |year=2008 |last1=Küpper |first1=Frithjof C. |last2=Carpenter |first2=Lucy J. |last3=McFiggans |first3=Gordon B. |last4=Palmer |first4=Carl J. |last5=Waite |first5=Tim J. |last6=Boneberg |first6=Eva-Maria |last7=Woitsch |first7=Sonja |last8=Weiller |first8=Markus |last9=Abela |first9=Rafael |last10=Grolimund |first10=Daniel |last11=Potin |first11=Philippe |last12=Butler |first12=Alison |last13=Luther |first13=George W. |last14=Kroneck |first14=Peter M. H. |last15=Meyer-Klaucke |first15=Wolfram |last16=Feiters |first16=Martin C. |journal=Proceedings of the National Academy of Sciences |volume=105 |issue=19 |pages=6954–8 |jstor=25461906 |bibcode=2008PNAS..105.6954K |pmid=18458346 |pmc=2383960}}</ref>
The fish used as sources 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 acid]]s, together with a high quantity of [[antioxidant]]s such as [[iodide]] and [[selenium]], from microalgae, where these antioxidants are able to protect the fragile polyunsaturated lipids from [[Lipid peroxidation|peroxidation]].<ref name="venturi">{{cite journal |author=Venturi S, Donati FM, Venturi A, Venturi M |title=Environmental iodine deficiency: A challenge to the evolution of terrestrial life? |journal=Thyroid |volume=10 |issue=8 |pages=727–9 |year=2000|pmid=11014322 |doi=10.1089/10507250050137851}}</ref><ref name="venturi2">{{cite journal |author=Venturi S, Venturi M |title=Evolution of Dietary Antioxidant Defences |year=2007 |journal=European Epi-Marker |volume=11 |issue=3 |pages=1–12}}</ref><ref>{{cite journal |doi=10.1073/pnas.0709959105 |title=Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry |year=2008 |last1=Küpper |first1=Frithjof C. |last2=Carpenter |first2=Lucy J. |last3=McFiggans |first3=Gordon B. |last4=Palmer |first4=Carl J. |last5=Waite |first5=Tim J. |last6=Boneberg |first6=Eva-Maria |last7=Woitsch |first7=Sonja |last8=Weiller |first8=Markus |last9=Abela |first9=Rafael |last10=Grolimund |first10=Daniel |last11=Potin |first11=Philippe |last12=Butler |first12=Alison |last13=Luther |first13=George W. |last14=Kroneck |first14=Peter M. H. |last15=Meyer-Klaucke |first15=Wolfram |last16=Feiters |first16=Martin C. |journal=Proceedings of the National Academy of Sciences |volume=105 |issue=19 |pages=6954–8 |jstor=25461906 |bibcode=2008PNAS..105.6954K |pmid=18458346 |pmc=2383960}}</ref>

Revision as of 20:22, 28 April 2015

A typical fish oil softgel

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,[1][2] and have other health benefits. Fish oils also contain docosapentaenoic acid (DPA), an intermediary of EPA and DHA that studies suggest contributes to cardiovascular, cognitive, and neurological health. [3]

The fish used as sources 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.[4][5][6]

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 toxic contaminants such as mercury, dioxin, PCBs and chlordane.[7] 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.[8]

Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[9] 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%.[10] They also differ in their effects on organ lipids.[9] 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.[11] 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.[11]

The omega-3 fatty acids in fish oil are thought to be beneficial in treating hypertriglyceridemia, and possibly beneficial in preventing heart disease.[12] Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression,[13][14] anxiety,[15][16][17] cancer, and macular degeneration, yet benefits in these conditions have not been verified.[12]

Uses

Often marketed and sold for consumption as part of the diet or in dietary supplements in contemporary societies, fish oils also have found roles in external use, as emollients[18] or as general ointments[19] as well as in body art,[20] or for alleged insulation against cold.[21]

Nutritional details

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 oils, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[22]

Grams of omega-3 fatty acids per 3oz (85g) serving of popular fish.[23][24]
Common name grams
Herring, sardines 1.3–2
Spanish mackerel, Atlantic, Pacific 1.1–1.7
Salmon 1.1–1.9
Halibut 0.60–1.12
Tuna 0.21–1.1
Swordfish 0.97
Greenshell/lipped mussels 0.95[25]
Tilefish 0.9
Tuna (canned, light) 0.17–0.24
Pollock 0.45
Cod 0.15–0.24
Catfish 0.22–0.3
Flounder 0.48
Grouper 0.23
Mahi mahi 0.13
Orange roughy 0.028
Red snapper 0.29
Shark 0.83
King mackerel 0.36
Hoki (blue grenadier) 0.41
Gemfish 0.40
Blue eye cod 0.31
Sydney rock oysters 0.30
Tuna, canned 0.23
Snapper 0.22
Barramundi, saltwater 0.100
Giant tiger prawn 0.100

For comparison, note the omega-3 levels in some common non-fish foods:

Grams of omega-3 fatty acids per 3oz (85g) serving of common non-fish foods.[23]
Name grams
flaxseeds 19.55
chia seeds 14.8
hemp seeds 7.4
walnut 1.7
Soybean 1.1
butter 0.27
Eggs, large regular 0.109[25]
Lean red meat 0.031
Turkey 0.030
Cereals, rice, pasta, etc. 0.00
Fruit 0.00
Milk regular 0.00
Regular bread 0.00
Vegetables 0.00

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.[citation needed] Peru continues to be the main fish oil producer worldwide, with about one fourth of total fish oil production.[citation needed]

Health effects

Prostate cancer

The effects of fish oil consumption by humans on prostate cancer is not conclusive.[26] 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,[27] and some evidence of an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk.[28]

Cardiovascular

The American Heart Association recommends the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautions pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish.[29] 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 (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/omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke."[12]

There is also some evidence that fish oil may have a beneficial effect on certain abnormal heart rhythms.[30][31]

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.[32] 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.[33]

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.[34]

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[35] 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.[36]

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.[37][38] Reduced levels of aggression have also been found in schoolchildren and young adults when their diets were supplemented with fish oil.[39][40]

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.[41] 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.[42]

The largest controlled study to date found no cognitive benefit after two years in the elderly.[43][44]

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.[45][46] He credits Donald O. Rudin for pioneering this view in 1981.[47][48]

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."[13] 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.[17]

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."[49] Another study published in October 2007 found that fish oil supplements conferred no additional benefits beyond those conferred by standard treatment.[50] 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.[51]

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.[52]

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."[53]

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".[54]

Psoriasis

Diets supplemented with cod liver oil have shown beneficial effects on psoriasis.[55]

Pregnancy

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.[56] 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.[56]

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.[57]

Crohn's disease

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.[58]

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.[59] 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.[60]

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.[61]

Mercury

While a serving of fish may contain anywhere from 10 to 1,000 ppb of mercury,[62] fish oil supplements have not been found to contain similar mercury levels[citation needed].

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.[63] 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.[64]

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.[61] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[63]

EPA and DHA content

Some countries[which?] recommend a combined daily intake of 300–500 mg while some countries like the US do not have a recommendation for EPA and DHA.[citation needed] The American Heart Association recommends 250–500 mg/day of EPA and DHA.[29] 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[which?] 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.[63] A 2012 report claims 4 of 35 fish oil supplements it covered contained less[quantify] EPA or DHA than was claimed on the label, and 3 of 35 contained more[quantify][63] A ConsumerLab.com publication in 2010 claims 3 of 24 fish oil supplements it covered contained less[quantify] EPA and/or DHA than was claimed on the label.[59] However, the bioavailability of EPA and DHA from both capsular and emulsified fish oils has been shown to be high. [65]

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[which?] with enteric-coated pill released ingredients prematurely[clarification needed] ; Consumerlab.com claims in its publication that there were problems in results of tests it ordered in 2012.[59] Fish oils are best tolerated when taken with meals, and, if possible, should be taken in equally divided doses throughout the day.[citation needed]

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".[66]

Maximum intake

The FDA says it is safe to take up to 3000 mg of omega-3 per day.[67] (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 Inuit and found an average intake of 5700 mg of omega-3 EPA per day.[68] 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.[69]

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).[70]

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,[71][72] 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.[73]

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.[74][75]

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."[76]

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."[77] 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.[78]

See also

Notes

  1. ^ Moghadasian, Mohammed H. (2008). "Advances in Dietary Enrichment with N-3 Fatty Acids". Critical Reviews in Food Science and Nutrition. 48 (5): 402–10. doi:10.1080/10408390701424303. PMID 18464030.
  2. ^ Cleland, Leslieg; James, Michaelj; Proudman, Susannam (2006). "Fish oil: What the prescriber needs to know". Arthritis Research & Therapy. 8 (1): 679–81. doi:10.1186/ar1876. PMC 1526555. PMID 16542466.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Byelashov, Alex. “DPA on the Rise.” Natural Products Insider. 2011.
  4. ^ Venturi S, Donati FM, Venturi A, Venturi M (2000). "Environmental iodine deficiency: A challenge to the evolution of terrestrial life?". Thyroid. 10 (8): 727–9. doi:10.1089/10507250050137851. PMID 11014322.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Venturi S, Venturi M (2007). "Evolution of Dietary Antioxidant Defences". European Epi-Marker. 11 (3): 1–12.
  6. ^ Küpper, Frithjof C.; Carpenter, Lucy J.; McFiggans, Gordon B.; Palmer, Carl J.; Waite, Tim J.; Boneberg, Eva-Maria; Woitsch, Sonja; Weiller, Markus; Abela, Rafael; Grolimund, Daniel; Potin, Philippe; Butler, Alison; Luther, George W.; Kroneck, Peter M. H.; Meyer-Klaucke, Wolfram; Feiters, Martin C. (2008). "Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry". Proceedings of the National Academy of Sciences. 105 (19): 6954–8. Bibcode:2008PNAS..105.6954K. doi:10.1073/pnas.0709959105. JSTOR 25461906. PMC 2383960. PMID 18458346.
  7. ^ EPA (31 January 2007). "Fish Consumption Advisories". Retrieved 8 February 2007.
  8. ^ FAO: World Review of Fisheries and Aquaculture 2008: Highlights of Special Studies Rome.
  9. ^ a b Innis, Sheila M.; Rioux, France M.; Auestad, Nancy; Ackman, Robert G. (1995). "Marine and freshwater fish oil varying in arachidonic, eicosapentaenoic and docosahexaenoic acids differ in their effects on organ lipids and fatty acids in growing rats". The Journal of Nutrition. 125 (9): 2286–93. PMID 7666244.
  10. ^ Gruger, E. H.; Nelson, R. W.; Stansby, M. E. (1 October 1964). "Fatty acid composition of oils from 21 species of marine fish, freshwater fish and shellfish". Journal of the American Oil Chemists Society. 41 (10): 662–7. doi:10.1007/BF02661403.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ a b Philibert, A; Vanier, C; Abdelouahab, N; Chan, HM; Mergler, D (December 2006). "Fish intake and serum fatty acid profiles from freshwater fish". The American journal of clinical nutrition. 84 (6): 1299–307. PMID 17158409.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ a b c NIH Medline Plus. "MedlinePlus Herbs and Supplements: Omega-3 fatty acids, fish oil, alpha-linolenic acid". Retrieved 14 February 2006.
  13. ^ a b Su, Kuan-Pin; Huang, Shih-Yi; Chiu, Chih-Chiang; Shen, Winston W. (2003). "Omega-3 fatty acids in major depressive disorder". European Neuropsychopharmacology. 13 (4): 267–71. doi:10.1016/S0924-977X(03)00032-4. PMID 12888186.
  14. ^ Naliwaiko, K.; Araújo, R.L.F.; Da Fonseca, R.V.; Castilho, J.C.; Andreatini, R.; Bellissimo, M.I.; Oliveira, B.H.; Martins, E.F.; Curi, R.; Fernandes, L.C.; Ferraz, A.C. (2004). "Effects of Fish Oil on the Central Nervous System: A New Potential Antidepressant?". Nutritional Neuroscience. 7 (2): 91–9. doi:10.1080/10284150410001704525. PMID 15279495.
  15. ^ Green, Pnina; Hermesh, Haggai; Monselise, Assaf; Marom, Sofi; Presburger, Gadi; Weizman, Abraham (2006). "Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder". European Neuropsychopharmacology. 16 (2): 107–13. doi:10.1016/j.euroneuro.2005.07.005. PMID 16243493.
  16. ^ Yehuda, Shlomo; Rabinovitz, Sharon; Mostofsky, David I. (2005). "Mixture of essential fatty acids lowers test anxiety". Nutritional Neuroscience. 8 (4): 265–7. doi:10.1080/10284150500445795. PMID 16491653.
  17. ^ a b Nemets, B.; Stahl, Z; Belmaker, RH (2002). "Addition of Omega-3 Fatty Acid to Maintenance Medication Treatment for Recurrent Unipolar Depressive Disorder". American Journal of Psychiatry. 159 (3): 477–9. doi:10.1176/appi.ajp.159.3.477. PMID 11870016.
  18. ^ Talakoub, Lily; Neuhaus, Isaac M.; Yu, Siegrid S. (2008). "Chapter 2: Cosmoceuticals". In Alam, Murad; Gladstone, Hayes B.; Tung, Rebecca (eds.). Cosmetic Dermatology. Requisites in dermatology. Elsevier Health Sciences. p. 9. ISBN 9780702031434. Retrieved 23 October 2014. Other oils used as emollients include fish oil, petrolatum, shea butter, and sunflower seed oil.
  19. ^ Burch, Ernest S. (2006). Social Life in Northwest Alaska: The Structure of Iñupiaq Eskimo Nations. University of Alaska Press. p. 278. ISBN 9781889963921. Retrieved 23 October 2014. Oil was also used externally as an ointment to heal cold sores, cuts, insect bites, frostbite, rashes - in short, skin problems of all kinds. Duck or goose body-cavity fat was apparently as useful as seal or fish oil in dealing with skin problems.
  20. ^ Heartney, Eleanor (2007). "Zhang Huan: Becoming the Body". Zhang Huan: Altered States. Charta and Asia Society. ISBN 978-8881586417. Retrieved 23 October 2014. This becomes abundantly clear in the work of Chinese body artist Zhang Huan. In the course of his career, Zhang Huan has subjected himself to painful trials: sitting motionless for hours in an outhouse covered in honey and fish oil while flies crawled over his body [...].
  21. ^ Ilse Schreiber: Die Schwestern aus Memel (1936), quoted, and extract translated in: Strzelczyk, Florentine (2014). "16: 'Fighting against Manitou': German Identity and Ilse Schreiber's Canada Novels Die Schwestern aus Memel (1936) and Die Flucht in Paradies (1939)". In McFarland, Rob; James, Michelle Stott (eds.). Sophie Discovers Amerika: German-Speaking Women Write the New World. Studies in German Literature Linguistics and Culture. Vol. 148. Boydell & Brewer. p. 207. ISBN 9781571135865. Hoffentlich zogen die Eltern in eine Gegend, wo es recht viele Eingeborene gab. Indianer, die nur von Jagd und Fischfang leben. Ach, und womöglich Eskimos, die sich mit Tran einschmieren, um sich gegen die Kälte zu schützen und rohes Fleisch essen [...]. [She hoped her parents would move to an area where there were many aboriginals. Indians who live solely by hunting and fishing. Oh, and if possible Eskimos who smear themselves with fish oil to protect themselves from the cold, and who eat raw meat.]
  22. ^ Falk-Petersen, S.; Sargent, J. R.; Henderson, J.; Hegseth, E. N.; Hop, H.; Okolodkov, Y. B. (1998). "Lipids and fatty acids in ice algae and phytoplankton from the Marginal Ice Zone in the Barents Sea". Polar Biology. 20 (1): 41–7. doi:10.1007/s003000050274. INIST 2356641.
  23. ^ a b "Fish, Levels of Mercury and Omega-3 Fatty Acids". American Heart Association. Retrieved 6 October 2010.
  24. ^ Kris-Etherton, Penny M.; William S. Harris, Lawrence J. Appel (2002). "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease". Circulation. 106 (21): 2747–57. doi:10.1161/01.CIR.0000038493.65177.94. PMID 12438303.
  25. ^ a b "Omega-3 Centre". Omega-3 sources. Omega-3 Centre. Archived from the original on 18 July 2008. Retrieved 27 July 2008.
  26. ^ Heinze, VM; Actis, AB (February 2012). "Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review". International journal of food sciences and nutrition. 63 (1): 66–78. doi:10.3109/09637486.2011.598849. PMID 21762028.
  27. ^ 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.
  28. ^ Brasky TM, Darke AK, Song X; et al. (August 2013). "Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial". J. Natl. Cancer Inst. 105 (15): 1132–41. doi:10.1093/jnci/djt174. PMC 3735464. PMID 23843441. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  29. ^ a b "Fish and Omega-3 Fatty Acids". American Heart Association. Retrieved 9 February 2007. Cite error: The named reference "AHA" was defined multiple times with different content (see the help page).
  30. ^ Charnock John S (1999). "The role of omega-3 polyunsaturated fatty acid-enriched diets in the prevention of ventricular fibrillation" (PDF). Asia Pacific Journal of Clinical Nutrition. 8 (3): 226–30. doi:10.1046/j.1440-6047.1999.00115.x. PMID 24394167.
  31. ^ Li G-R Sun H-Y, Zhang X-H Cheng L-C, Chiu S-W Tse H-F, Lau C-P (2009). "Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+currents and Na+current in human atrial myocytes". Cardiovasc Res. 81 (2): 286–93. doi:10.1093/cvr/cvn322. PMID 19029136.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Nair, G. M.; Connolly, S. J. (2008). "Should patients with cardiovascular disease take fish oil?". Canadian Medical Association Journal. 178 (2): 181–2. doi:10.1503/cmaj.071654. PMC 2174997. PMID 18195293.
  33. ^ Rizos, E. C.; Ntzani, E. E.; Bika, E; Kostapanos, MS; Elisaf, MS (2012). "Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events: A Systematic Review and Meta-analysis". Journal of the American Medical Association. 308 (10): 1024–33. doi:10.1001/2012.jama.11374. PMID 22968891.
  34. ^ "Omega-3 fatty acids, fish oil, alpha-linolenic acid". Retrieved 4 February 2014. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  35. ^ Huan, M; Hamazaki, K; Sun, Y; Itomura, M; Liu, H; Kang, W; Watanabe, S; Terasawa, K; Hamazaki, T (2004). "Suicide attempt and n-3 fatty acid levels in red blood cells: A case control study in china". Biological Psychiatry. 56 (7): 490–6. doi:10.1016/j.biopsych.2004.06.028. PMID 15450784.
  36. ^ Mischoulon, David; Papakostas, George I.; Dording, Christina M.; Farabaugh, Amy H.; Sonawalla, Shamsah B.; Agoston, A. Monica; Smith, Juliana; Beaumont, Erin C.; Dahan, Liat E.; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio (2009). "A Double-Blind, Randomized Controlled Trial of Ethyl-Eicosapentaenoate for Major Depressive Disorder". The Journal of Clinical Psychiatry. 70 (12): 1636–44. doi:10.4088/JCP.08m04603. PMC 2918427. PMID 19709502.
  37. ^ Mihm, Stephen (16 April 2006). "Does Eating Salmon Lower the Murder Rate?". New York Times Magazine. Retrieved 8 February 2007.
  38. ^ Gesch, CB; Hammond, SM; Hampson, SE; Eves, A; Crowder, MJ (2002). "Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners" (PDF). British Journal of Psychiatry. 181 (1): 22–8. doi:10.1192/bjp.181.1.22. PMID 12091259.
  39. ^ Itomura, M.; Hamazaki, K.; et al. (2005). "The effect of fish oil on physical aggression in schoolchildren". Journal of Nutritional Biochemistry. 16 (3): 163–71. doi:10.1016/j.jnutbio.2004.10.009. {{cite journal}}: Explicit use of et al. in: |first2= (help)
  40. ^ Benton, D. (2007). "The impact of diet on anti-social, violent and criminal behaviour" (PDF). Neuroscience & Biobehavioral Reviews. 31 (5): 752–74. doi:10.1016/j.neubiorev.2007.02.002.
  41. ^ Amminger, G. P.; Schäfer, M. R.; Papageorgiou, K.; Klier, C. M.; Cotton, S. M.; Harrigan, S. M.; MacKinnon, A.; McGorry, P. D.; Berger, G. E. (2010). "Long-Chain ω-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial". Archives of General Psychiatry. 67 (2): 146–54. doi:10.1001/archgenpsychiatry.2009.192. PMID 20124114.
  42. ^ Knapp, M. (1997). "Costs of schizophrenia". The British Journal of Psychiatry. 171 (6): 509–18. doi:10.1192/bjp.171.6.509. PMID 9519088. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)
  43. ^ Dangour, AD; Allen, E; Elbourne, D; Fasey, N; Fletcher, AE; Hardy, P; Holder, GE; Knight, R; Letley, L; Richards, M.; Uauy, R.; et al. (2010). "Effect of 2-y n−3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people". American Journal of Clinical Nutrition. 91 (6): 1725–32. doi:10.3945/ajcn.2009.29121. PMID 20410089. {{cite journal}}: Explicit use of et al. in: |first9= (help); Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
  44. ^ Fish oil 'no benefit' to elderly NHS, 29 April 2010.
  45. ^ Stoll, Andrew L.; Severus, W. Emanuel; Freeman, Marlene P.; Rueter, Stephanie; Zboyan, Holly A.; Diamond, Eli; Cress, Kimberly K.; Marangell, Lauren B. (1999). "Omega 3 Fatty Acids in Bipolar Disorder". Archives of General Psychiatry. 56 (5): 407–12. doi:10.1001/archpsyc.56.5.407. PMID 10232294.
  46. ^ Stoll, Andrew L. (2002). The Omega-3 Connection: The Groundbreaking Omega-3 Antidepression Diet and Brain Program. Free Press. ISBN 0-684-87139-4.[page needed]
  47. ^ Baumel, Syd (Fall 2001). "Your Brain on Fats". The Aquarian. The Aquarian Newspaper.
  48. ^ Rudin, DO (1981). "The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: Substrate pellagra". Biological Psychiatry. 16 (9): 837–50. PMID 7028146.
  49. ^ Silvers, K; Woolley, C; Hamilton, F; Watts, P; Watson, R (2005). "Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression". Prostaglandins, Leukotrienes and Essential Fatty Acids. 72 (3): 211–8. doi:10.1016/j.plefa.2004.11.004.
  50. ^ Grenyer, B; Crowe, T; Meyer, B; Owen, A; Grigonis-Deane, E; Caputi, P; Howe, P (2007). "Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 31 (7): 1393–6. doi:10.1016/j.pnpbp.2007.06.004. PMID 17659823.
  51. ^ Montgomery P, Richardson AJ (2008). Montgomery, Paul (ed.). "Omega-3 fatty acids for bipolar disorder". Cochrane Database of Systematic Reviews (2): CD005169. doi:10.1002/14651858.CD005169.pub2. PMID 18425912.
  52. ^ Martins, Julian G (2009). "EPA but Not DHA Appears to Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials". Journal of the American College of Nutrition. 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID 20439549.
  53. ^ Bloch, M H; Hannestad, J (2011). "Omega-3 fatty acids for the treatment of depression: Systematic review and meta-analysis". Molecular Psychiatry. 17 (12): 1272–82. doi:10.1038/mp.2011.100. PMC 3625950. PMID 21931319.
  54. ^ Sifferlin, Alexandra (13 June 2012). "Fish Oil Fail: Omega-3s May Not Protect Brain Health After All". Time. Retrieved 19 June 2012.
  55. ^ Wolters, M. (2005). "Diet and psoriasis: experimental data and clinical evidence". British Journal of Dermatology. 153 (4): 706–14. doi:10.1111/j.1365-2133.2005.06781.x. PMID 16181450.
  56. ^ a b Jensen, Craig L.; Voigt, Robert G.; Llorente, Antolin M.; Peters, Sarika U.; Prager, Thomas C.; Zou, Yali L.; Rozelle, Judith C.; Turcich, Marie R.; Fraley, J. Kennard; Anderson, Robert E.; Heird, William C. (2010). "Effects of Early Maternal Docosahexaenoic Acid Intake on Neuropsychological Status and Visual Acuity at Five Years of Age of Breast-Fed Term Infants". The Journal of Pediatrics. 157 (6): 900–5. doi:10.1016/j.jpeds.2010.06.006. PMID 20655543.
  57. ^ Calder, Philip C.; Kremmyda, Lefkothea-Stella; Vlachava, Maria; Noakes, Paul S.; Miles, Elizabeth A. (2010). "Is there a role for fatty acids in early life programming of the immune system?". Proceedings of the Nutrition Society. 69 (3): 373–80. doi:10.1017/S0029665110001552. PMID 20462467.
  58. ^ Lev-Tzion, R; Griffiths, AM; Leder, O; Turner, D (28 February 2014). "Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease". The Cochrane database of systematic reviews. 2: CD006320. doi:10.1002/14651858.CD006320.pub4. PMID 24585498.
  59. ^ a b c "ConsumerLab.com Finds Quality Problems with Nearly Thirty Percent of Fish Oil Supplements Reviewed; "Fishy" Claims Identified: Softgels and Liquids for Adults, Children and Pets Tested, Including Krill Oil and Algal Oil Supplements". ConsumerLab.com. 28 September 2010. Retrieved 20 October 2012.[dubiousdiscuss]
  60. ^ Reviews of Supplements and Health Products ConsumerLab.
  61. ^ a b Aursand, Marit; Mozuraityte, Revilija; Hamre, Kristin; Knutsen, Helle; Maage, Amund; Arukwe, Augustine (2011). Description of the processes in the value chain and risk assessment of decomposition substances and oxidation products in fish oils (PDF). Norwegian Scientific Committee for Food Safety. ISBN 978-82-8259-035-8. Retrieved 19 October 2012.[page needed]
  62. ^ Mercury Levels in Commercial Fish and Shellfish (1990–2010) U.S. Food and Drug Administration. Accessed 25 March 2013.
  63. ^ a b c d "ConsumerLab.com Review: Fish Oil and Omega-3 Fatty Acid Supplements Review (Including Krill, Algae, and Calamari Oil)". ConsumerLab.com. 13 August 2012. Retrieved 19 October 2012.(registration required)
  64. ^ "ConsumerLab.com Review: Fish Oil and Omega-3 Fatty Acid Supplements Review (Including Krill, Algae, and Calamari Oil): Contaminants in Fish Vs. Supplements: Contaminants in Fish vs. Supplements". ConsumerLab.com. 13 August 2012. Retrieved 19 October 2012.(registration required)
  65. ^ Raatz, SK; Redmon, JB; Wimmergren, N; Donadio, JV; Bibus, DM (2009). "Enhanced absorption of omega-3 fatty acids after emulsified compared with encapsulated fish oil". Journal of the American Dietetic Association. 109: 1076–1081. doi:10.1016/j.jada.2009.03.006.
  66. ^ Villani, Anthony M; Crotty, Maria; Cleland, Leslie G; James, Michael J; Fraser, Robert J; Cobiac, Lynne; Miller, Michelle D (2013). "Fish oil administration in older adults: Is there potential for adverse events? A systematic review of the literature". BMC Geriatrics. 13 (1): 41. doi:10.1186/1471-2318-13-41. PMC 3664575. PMID 23634646.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  67. ^ Can you overdose on DHA and EPA? DHA/EPA Omega-3 Institute. Retrieved 4 November 2011.
  68. ^ Kantha, SS (1987). "Dietary effects of fish oils on human health: A review of recent studies". The Yale Journal of Biology and Medicine. 60 (1): 37–44. PMC 2590235. PMID 3551346.
  69. ^ "Scientific Opinion on the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)". EFSA Journal. EFSA. Retrieved 14 September 2014.
  70. ^ Lips, Paul (2003). "Hypervitaminosis a and Fractures". New England Journal of Medicine. 348 (4): 347–9. doi:10.1056/NEJMe020167. PMID 12540650.
  71. ^ Jess Halliday (13 April 2006). "Dioxins prompt second UK fish oil withdrawal". Retrieved 8 February 2007.
  72. ^ "Pollutants found in fish oil capsules". BBC News. 6 April 2002. Retrieved 8 February 2007.
  73. ^ International Fish Oil Standards.
  74. ^ Elisabeth Leamy (3 March 2010). "Lawsuit Raises Fish Oil Supplement Concerns". Retrieved 5 March 2010.
  75. ^ "Lawsuit says fish oil supplements contain PCB", San Francisco Chronicle, March 3, 2010.
  76. ^ Brustad, Magritt; Sandanger, Torkjel Manning; Andersen, Vegard; Lund, Eiliv (2007). "POP exposure from fish liver consumption and risk of cancer?the Norwegian Women and Cancer Study". Journal of Environmental Monitoring. 9 (7): 682–6. doi:10.1039/B706302B. PMID 17607388.
  77. ^ Foran, Stacy E.; Flood, James G.; Lewandrowski, Kent B. (2003). "Measurement of Mercury Levels in Concentrated Over-the-Counter Fish Oil Preparations: Is Fish Oil Healthier Than Fish?". Archives of Pathology & Laboratory Medicine. 127 (12): 1603–5. doi:10.1043/1543-2165(2003)1271603:MOMLIC2.0.CO;2. PMID 14632570.
  78. ^ Doughman, Scott D.; Krupanidhi, Srirama; Sanjeevi, Carani B. (2007). "Omega-3 Fatty Acids for Nutrition and Medicine: Considering Microalgae Oil as a Vegetarian Source of EPA and DHA". Current Diabetes Reviews. 3 (3): 198–203. doi:10.2174/157339907781368968. PMID 18220672.

References