First satellites

First satellites

Replica of the Sputnik 1

The first artificial satellite was Sputnik 1, launched by the Soviet Union on 4 October 1957 under the Sputnik program, with Sergei Korolev as chief designer. Sputnik 1 helped to identify the density of high atmospheric layers through measurement of its orbital change and provided data on radio-signal distribution in the ionosphere. The unanticipated announcement of Sputnik 1's success precipitated the Sputnik crisis in the United States and ignited the so-called Space Race within the Cold War.

In the context of activities planned for the International Geophysical Year (1957–1958), the White House announced on 29 July 1955 that the U.S. intended to launch satellites by the spring of 1958. This became known as Project Vanguard. On 31 July, the Soviet Union announced its intention to launch a satellite by the fall of 1957.

Sputnik 2 was launched on 3 November 1957 and carried the first living passenger into orbit, a dog named Laika.^[11]

In early 1955, after pressured by the American Rocket Society, the National Science Foundation, and the International Geophysical Year, the Army and Navy worked on Project Orbiter with two competing programs. The army used the Jupiter C rocket, while the civilian–Navy program used the Vanguard rocket to launch a satellite. Explorer 1 became the United States' first artificial satellite, on 31 January 1958.^[12] The information sent back from its radiation detector led to the discovery of the Earth's Van Allen radiation belts.^[13] The TIROS-1 spacecraft, launched on April 1, 1960, as part of NASA's Television Infrared Observation Satellite (TIROS) program, sent back the first television footage of weather patterns to be taken from space.^[14]

In June 1961, three and a half years after the launch of Sputnik 1, the United States Space Surveillance Network cataloged 115 Earth-orbiting satellites.^[15] Astérix or A-1 (initially conceptualized as FR.2 or FR-2) is the first French satellite. It was launched on 26 November 1965 by a Diamant A rocket from the CIEES launch site at Hammaguir, Algeria. With Astérix, France became the sixth country to have an artificial satellite and the third country to launch a satellite on its own rocket

France is the third country to launch a satellite on its own rocket, the Astérix, on 26 November 1965 by a Diamant A rocket from the CIEES launch site at Hammaguir, Algeria.

Early satellites were built to unique designs. With advancements in technology, multiple satellites began to be built on single model platforms called satellite buses. The first standardized satellite bus design was the HS-333 geosynchronous (GEO) communication satellite launched in 1972. Beginning in 1997, FreeFlyer is a commercial off-the-shelf software application for satellite mission analysis, design, and operations. 

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Satellite

From Wikipedia, the free encyclopedia

This article is about human-made satellites. For moons, see Natural satellite. For other uses, see Satellite (disambiguation).

Two CubeSats orbiting around Earth after being deployed from the ISS Kibō module's Small Satellite Orbital Deployer

A satellite or artificial satellite^[a] is an object, typically a spacecraft, placed into orbit around a celestial body. Satellites have a variety of uses, including communication relay, weather forecasting, navigation (GPS), broadcasting, scientific research, and Earth observation. Additional military uses are reconnaissance, early warning, signals intelligence and, potentially, weapon delivery. Other satellites include the final rocket stages that place satellites in orbit and formerly useful satellites that later become defunct.

Except for passive satellites, most satellites have an electricity generation system for equipment on board, such as solar panels or radioisotope thermoelectric generators (RTGs). Most satellites also have a method of communication to ground stations, called transponders. Many satellites use a standardized bus to save cost and work, the most popular of which is a small CubeSats. Similar satellites can work together as groups, forming constellations. Because of the high launch cost to space, satellites are designed to be as lightweight and robust as possible. Most communication satellites are radio relay stations in orbit and carry dozens of transponders, each with a bandwidth of tens of megahertz.

Satellites are placed from the surface to the orbit by launch vehicles, high enough to avoid orbital decay by the atmosphere. Satellites can then change or maintain the orbit by propulsion, usually by chemical or ion thrusters. As of 2018, about 90% of the satellites orbiting the Earth are in low Earth orbit or geostationary orbit; geostationary means the satellites stay still in the sky. Some imaging satellites chose a Sun-synchronous orbit because they can scan the entire globe with similar lighting. As the number of satellites and space debris around Earth increases, the threat of collision has become more severe. A small number of satellites orbit other bodies (such as the Moon, Mars, and the Sun) or many bodies at once (two for a halo orbit, three for a Lissajous orbit).

Earth observation satellites gather information for reconnaissance, mapping, monitoring the weather, ocean, forest, etc. Space telescopes take advantage of outer space's near perfect vacuum to observe objects with the entire electromagnetic spectrum. Because satellites can see a large portion of the Earth at once, communications satellites can relay information to remote places. The signal delay from satellites and their orbit's predictability are used in satellite navigation systems, such as GPS. Space probes are satellites designed for robotic space exploration outside of Earth, and space stations are in essence crewed satellites.

The first artificial satellite launched into the Earth's orbit was the Soviet Union's Sputnik 1, on October 4, 1957. As of December 31st 2022, there are 6,718 operational satellites in the Earth's orbit, of which 4,529 belong to the United States (3,996 commercial), 590 belong to China, 174 belong to Russia, and 1,425 belong to other nations.^[1]

History

See also: Timeline of first artificial satellites by country

Early proposals

The first published mathematical study of the possibility of an artificial satellite was Newton's cannonball, a thought experiment by Isaac Newton to explain the motion of natural satellites, in his Philosophiæ Naturalis Principia Mathematica (1687). The first fictional depiction of a satellite being launched into orbit was a short story by Edward Everett Hale, "The Brick Moon" (1869).^[2][3] The idea surfaced again in Jules Verne's The Begum's Fortune (1879).

In 1903, Konstantin Tsiolkovsky (1857–1935) published Exploring Space Using Jet Propulsion Devices, which was the first academic treatise on the use of rocketry to launch spacecraft. He calculated the orbital speed required for a minimal orbit, and inferred that a multi-stage rocket fueled by liquid propellants could achieve this.

Herman Potočnik explored the idea of using orbiting spacecraft for detailed peaceful and military observation of the ground in his 1928 book, The Problem of Space Travel. He described how the special conditions of space could be useful for scientific experiments. The book described geostationary satellites (first put forward by Konstantin Tsiolkovsky) and discussed the communication between them and the ground using radio, but fell short with the idea of using satellites for mass broadcasting and as telecommunications relays.^[4]

In a 1945 Wireless World article, English science fiction writer Arthur C. Clarke described in detail the possible use of communications satellites for mass communications. He suggested that three geostationary satellites would provide coverage over the entire planet.^[5]: 1–2

In May 1946, the United States Air Force's Project RAND released the Preliminary Design of an Experimental World-Circling Spaceship, which stated "A satellite vehicle with appropriate instrumentation can be expected to be one of the most potent scientific tools of the Twentieth Century."^[6] The United States had been considering launching orbital satellites since 1945 under the Bureau of Aeronautics of the United States Navy. Project RAND eventually released the report, but considered the satellite to be a tool for science, politics, and propaganda, rather than a potential military weapon.^[7]

In 1946, American theoretical astrophysicist Lyman Spitzer proposed an orbiting space telescope.^[8]

In February 1954, Project RAND released "Scientific Uses for a Satellite Vehicle", by R. R. Carhart.^[9] This expanded on potential scientific uses for satellite vehicles and was followed in June 1955 with "The Scientific Use of an Artificial Satellite", by H. K. Kallmann and W. W. Kellogg.^[10]

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Omega-3 acid ethyl esters

From Wikipedia, the free encyclopedia

Omega-3-acid ethyl esters

Chemical structure of ethyl eicosapentaenoate, an important omega-3-acid ethyl ester
Combination of
Eicosapentaenoic acid	Antilipemic agent
Docosahexaenoic acid	Antilipemic agent
Clinical data
Trade names	Lovaza, Omtryg, others
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN US DailyMed: Omega-3-acid_ethyl_esters
Pregnancy category	AU: B1[1]
Routes of administration	By mouth
ATC code	none
Legal status
Legal status	UK: POM (Prescription only)[2] US: ℞-only In general: ℞ (Prescription only)
Identifiers
CAS Number	308081-97-2
DrugBank	DB09539
UNII	D87YGH4Z0Q
KEGG	D05255

Omega-3-acid ethyl esters are a mixture of ethyl eicosapentaenoic acid and ethyl docosahexaenoic acid, which are ethyl esters of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil.^[3] Together with dietary changes, they are used to treat high blood triglycerides which may reduce the risk of pancreatitis.^[3][4] They are generally less preferred than statins, and use is not recommended by NHS Scotland as the evidence does not support a decreased risk of heart disease.^[3][5][6] Omega-3-acid ethyl esters are taken by mouth.^[3]

Common side effects include burping, nausea, and an upset abdomen.^[3][5] Serious side effects may include liver problems and anaphylaxis.^[3] While use in pregnancy has not been well studied, some omega-3 fatty acids appear beneficial.^[1] How it works is not entirely clear.^[3]

Omega-3-acid ethyl ester medicines were approved for medical use in the European Union in 2000 and in the United States in 2004.^[3][6][7] Beyond the branded prescription formulation, it is also available as a generic medication and over the counter.^[3][5] In 2020, it was the 199th most commonly prescribed medication in the United States, with more than 2 million prescriptions.^[8][9]

Medical use

Omega-3 acid ethyl esters are used in addition to changes in diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dL) hypertriglyceridemia.^[10] In the European Union and other major markets outside the US, omega-3 acid ethyl esters are indicated for hypertriglyceridemia by itself, or in combination with a statin for people with mixed dyslipidemia.^[2][6]

Intake of large doses (2.0 to 4.0 g/day) of long-chain omega-3 fatty acids as prescription drugs or dietary supplements are generally required to achieve significant (> 15%) lowering of triglycerides, and at those doses, the effects can be significant (from 20% to 35% and even up to 45% in individuals with levels greater than 500 mg/dL). It appears that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglycerides, but DHA appears to raise LDL cholesterol more than EPA, while DHA raises HDL cholesterol while EPA does not.^[11]

Other fish-oil based drugs

Other omega-3 fish oil-based prescription drugs on the market have similar uses and mechanisms of action.^[12]

• Ethyl eicosapentaenoic acid (Vascepa). EPA-only ethyl esters.^[13]
• Omega-3 carboxylic acids (Epanova). This product contains free fatty acids, not ethyl esters.^[14] It is currently withdrawn from the market by the manufacturer (AstraZeneca) and is thus unavailable to patients.^[15] AstraZeneca voluntarily discontinued Phase III clinical trials for futility.^[16]

Dietary supplements

There are many fish oil dietary supplements on the market.^[17] There appears to be little difference in effect between dietary supplement and prescription forms of omega-3 fatty acids as to ability to lower triglycerides, but the ethyl ester products work less well when taken on an empty stomach or with a low-fat meal.^[11] The ingredients of dietary supplements are not as carefully controlled as prescription products and have not been tested in clinical trials as such drugs have.^[18] Prescription omega-3 products are more concentrated, requiring fewer softgels for the same daily dose.^[17]

In people with CKD who require hemodialysis, there is a risk that vascular blockage due to clotting, may prevent dialysis therapy from being possible. Omega-3 fatty acids contribute to the production of eicosanoid molecules that reduce clotting. However, a Cochrane review in 2018 did not find clear evidence that omega-3 supplementation has any impact on the prevention of vascular blockage in people with CKD.^[19] There was also moderate certainty that supplementation did not prevent hospitalisation or death within a 12-month period.^[19]

Side effects

Special caution should be taken with people who have fish and shellfish allergies.^[10] In addition, as with other omega-3 fatty acids, taking omega-3 acid ethyl esters puts people who are on anticoagulants at risk for prolonged bleeding time.^[10][11]

Side effects include stomach ache, burping, and a bad taste; some people on very high doses (8g/day) in clinical trials had atrial fibrillation.^[10]

Omega-3 acid ethyl esters have not been tested in pregnant women and are rated pregnancy category C; it is excreted in breast milk and the effects on infants are not known.^[10]

Pharmacology

After ingestion, omega-3-acid ethyl esters are metabolized mostly in the liver like other dietary fatty acids.^[2]

Mechanism of action

Omega-3-acid ethyl esters, like other omega-3 fatty acid-based drugs, appears to reduce production of triglycerides in the liver and to enhance clearance of triglycerides from circulating very low-density lipoprotein (VLDL) particles. The way it does that is not clear, but potential mechanisms include increased breakdown of fatty acids; inhibition of diglyceride acyltransferase, which is involved in biosynthesis of triglycerides in the liver; and increased activity of lipoprotein lipase in blood.^[2][12] The synthesis of triglycerides is reduced in the liver because EPA and DHA are poor substrates for the enzymes responsible for triglyceride synthesis.

Physical and chemical properties

The active ingredient is concentrated omega-3 acid ethyl esters that are made from fish body oils that are purified and esterified.^[20] For the Lovaza product, each 1000 mg softgel capsule contains 840 mg omega-3 fatty acids: eicosapentaenoic acid ethyl ester (460 mg) and docosahexaenoic acid ethyl ester (380 mg).^[2]

History

Pronova BioPharma ASA had its roots in Norway's codfish liver oil industry. The company was founded in 1991 as a spinout from the JC Martens company, which in turn was founded in 1838 in Bergen, Norway.^[21] Pronova developed the concentrated omega-3-acid ethyl esters formulation that is the active pharmaceutical ingredient of Lovaza.^[20]

Pronova won approvals to market the drug, called Omacor in Europe (and initially in the US), in several European countries in 2001 after conducting a three and a half year trial in 11,000 subjects;^[22] The company partnered with other companies like Pierre Fabre in France.^[23] In 2004, Pronova licensed the US and Puerto Rican rights to Reliant Therapeutics, whose business model was in-licensing of cardiovascular drugs.^[24] In that same year, Reliant and Pronova won FDA approval for the drug,^[25] and it was launched in the US and Europe in 2005. Global sales in 2005 were $144M, and by 2008, they were $778M.^[26] In 2007 GlaxoSmithKline acquired Reliant for $1.65 billion in cash.^[27]

In 2009, generic companies Teva Pharmaceuticals and Par Pharmaceutical made clear their intentions to file Abbreviated New Drug Applications ("ANDAs") to bring generics to market, and in April 2009, Pronova sued them from infringing the key US patents covering Lovaza, US 5,656,667 (due to expire in April 2017), US 5,502,077 (exp March 2013). Subsequently, in May 2012, a district court ruled in Pronova's favor, saying that the patents were valid.^[28][29][30] The generic companies appealed, and in September 2013, the Federal Circuit reversed, saying that because more than one year before Pronova's predecessor company applied for a patent, it had sent samples of the fish oil used in Lovaza to a researcher for testing. This event thus constituted "public use" that invalidated the patent in question.^[31][32] Generic versions of Lovaza were introduced in America in April 2014.^[33]

Pronovo has continued to manufacture the ingredien

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Prescription fish oil-based medications

Prescription fish oil-based medications

See also: Omega-3 acid ethyl esters and Fish oil (medical use)

Fish oil itself is available as a prescription, but the majority of fish oil products available via prescription are derivatives of fish oil. Such products are described elsewhere in this article. These preparations, with the purpose of treating or preventing medical disorder, are only available with a doctor's prescription. In the US, such prescriptions undergo the same Food and Drug Administration (FDA) regulatory requirements as other prescription medications, including with regard to both efficacy and safety.^[61] Purity is also regulated by the FDA. The prescription fish oil derivative medicines differ from over-the-counter fish oil supplements.^[62] Prescription fish oil is considered a safe and effective option to reduce triglycerides. There are various prescription fish oil products that have been approved and permitted by the FDA for decreasing triglyceride levels. Prescription fish oil products having DHA work by raising LDL-C levels to reduce triglycerides, like fibrates.^[63] Heart experts advise that prescription fish oil helps in decreasing additional levels of blood fats. Prescription fish oils might only help when triglycerides reach a specific upper level.^[64] Prescription fish oil pills, capsules and tablets have more omega-3 fatty acids than those which are non-prescription. The FDA regularly monitors prescription fish oil for standards like purity and for quality and safety.^[65]

As of 2019, four fish oil-based prescription drugs have been approved in the United States for the treatment of hypertriglyceridemia,^[8] namely:

1. Epanova (omega-3 carboxylic acids) was approved on 23 April 2014.^[66][67][68] Clinical trial on mixed dyslipidaemia (hypertriglyceridemia with hypocholesterolemia) started in 2014^[69] found that it has no medical benefits, and the clinical trial was called off on 13 January 2019.^[70] Although FDA-approved, Epanova is not available in any market.
2. Lovaza (omega-3 acid ethyl esters) was approved on 10 November 2004.^{[71][72][73][74]}
3. Omtryg (omega-3 acid ethyl esters) was approved on 23 April 2014.^[75][76][77]
4. Vascepa (ethyl eicosapentaenoic acid; icosapent ethyl) was approved on 26 July 2012.^[78][79][80] On 13 December 2019, the FDA also approved it as the first drug specifically "to reduce cardiovascular risk among patients with elevated triglyceride levels." Vascepa is not approved as a monotherapy for lowering TGs: it must be taken with a statin, per product labeling.^[81]

Some fish-oil products are approved for parenteral nutrition:

1. Omegaven, approved in July 2018, is indicated as a source of calories and fatty acids in children with parenteral nutrition-associated cholestasis (PNAC).^[82][83][84]
2. Smoflipid, approved in July 2016, is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.^[85][86][87]

Dangers

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".^[88]

Maximum intake

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.^[89] 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.^[90] 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.^[91]

Research

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.^[92][93]

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).^[94]

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 polychlorinated biphenyl (PCB) levels that exceeded the European Union maximum limits in several fish oil brands,^[95][96] 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.^[97]

A March 2010 lawsuit filed by a California environmental group claimed that eight brands of fish oil supplements contained excessive levels of PCBs, 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.^[98][99]

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."^[100]

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.^[101]

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Mental health

Mental health

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.^[43]

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.^[44]

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."^[45]

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."^[46]

Antidepressant

A 2019 meta-analysis concluded that EPA ≥ 60% at a dosage of ≤1 g/d may have antidepressant effect.^[47]

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".^[48]

Psoriasis

Diets supplemented with cod liver oil have shown beneficial effects on psoriasis.^[49]

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.^[50] 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.^[50]

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.^[51]

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.^[52]

Supplements

Fish oil capsules

Fish oil is a commonly used dietary supplement, with sales in the US alone reaching $976 million in 2009.^[53] 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.^[54]

Formulation

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.^[53] Fish oil products may use other techniques to hide the fishy taste. For example, added lemon or strawberry flavor tends to produce a more agreeable product^[55] and are usually present in fish oil gummies.

EPA and DHA content

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.^[56] However, the bioavailability of EPA and DHA from both capsular and emulsified fish oils has been shown to be high.^[57] 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.^[53] A 2012 report stated that 4 of 35 fish oil supplements that were tested contained less EPA or DHA than was claimed on the label, and 3 of 35 contained more.^[56]

Quality and concerns

Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems may include contamination, inaccurate listing of EPA and DHA levels, spoilage, and formulation issues.^[58]

Contamination

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".^[59] There appears to be little risk of contamination by microorganisms, proteins, lysophospholipids, cholesterol, and trans-fats.^[60]

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 US 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.^[56] 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.^[56]

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.^[60] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.^[56]

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Health effects of fish oil

Health effects

Kepler cod liver oil with malt extract

History

Fish oil became one of the earliest dietary supplements, and by the end of the 19th century, was used as a treatment for many diseases, including such ailments as tuberculosis and hysteria.^[17][18][19] The possible effects of fish oil and omega-3 fatty acids have since been studied in clinical depression,^[20][21] anxiety,^[22] cancer, and macular degeneration, yet they have not been proven effective.^[23]

Various recommendations

In a 2009 letter on a pending revision to the Dietary Guidelines for Americans, the American Heart Association recommended 250–500 mg/day of EPA and DHA.^[24] The Guidelines were revised again for 2015–2020; included is a recommendation that adults consume at least eight ounces of a variety of types of fish per week, equating to at least 250 mg/day of EPA + DHA.^{[citation needed]} The Food and Drug Administration recommends not exceeding 3 grams per day of EPA + DHA from all sources, with no more than 2 grams per day from dietary supplements.^[25]

Prostate cancer

The effect of fish oil consumption on prostate cancer is controversial.^[26][27] 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.^[28] Some evidence indicated an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk.^[29]

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".^[30]

Cardiovascular

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.^[31][32][33] In 2007, the American Heart Association recommended the consumption of 1 gram of fish oil daily,^[34] 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.^[35] (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."^[23]

There were studies to determine if fish oil had an effect on certain abnormal heart rhythms,^[36][37] although a 2012 meta-analysis found no significant effect.^[38]

A 2008 meta-study found fish oil supplementation did not demonstrate any preventative benefit to cardiac patients with ventricular arrhythmias.^[39] 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.^[40] 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.^[41]

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). Because omega-3 fatty acids can increase the risk of bleeding, a qualified healthcare provider should be consulted before supplementing with fish oil.^[42]

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Fish oil

From Wikipedia, the free encyclopedia

For Omegaven, see Fish oil (medical use).

Dietary fish oil is obtained by consuming fatty fish or supplements in pill form.

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.^[1][2] 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.^[3] Fish oil is used in aquaculture feed, in particular for feeding farmed salmon.^[4]

Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.^[5] 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%.^[6] They also differ in their effects on organ lipids.^[5] Studies have revealed that there is no relation between either 1) total fish intake or 2) estimated omega−3 fatty acid intake from all fish and serum omega−3 fatty acid concentrations.^[7] 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.^[7]

As of 2019, the US Food and Drug Administration (FDA) has approved four fish oil-based prescription drugs, namely Lovaza, Omtryg (both omega-3 acid ethyl esters), Vascepa (ethyl eicosapentaenoic acid), and Epanova (omega-3 carboxylic acids).^[8] None of these drugs is actually fish oil: they are all derivatives of acids found in fish oil.

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^[9] or as general ointments^[10] as well as in body art,^[11] or for alleged insulation against cold temperatures.^[12]

Fish oil rendering in Port Dover, Ontario, 1918

Food sources

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.^[13]

EPA and DHA are available as dietary supplements most commonly as fish oil capsules, softgels, and gummies,¹ krill oil, and less commonly as algae oil.² Generally, salmon oil has more DHA than EPA while other fish oils such as herring, mackerel, anchovies, sardines, and pollock have more EPA than DHA. (See Supplements section below.)

Grams of omega-3 fatty acids per 3 oz (85 g) serving of popular fish.^[14][15]

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[16]
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
Silver gemfish	0.40
Blue eye cod	0.31
Sydney rock oyster	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 3 oz (85 g) serving of common non-fish foods.^[14]

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[16]
Lean red meat	0.031
Turkey (bird)	0.030
Cereals, rice, pasta, etc.	0.00
Fruit	0.00
Milk, regular	0.00
Bread, regular	0.00
Vegetables	0.00

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