Jump to content

Omega-3 fatty acid

From Wikipedia, the free encyclopedia

Omega−3 fatty acids. , also called Omega−3 oils, ω−3 fatty acids, Ω-3 Fatty acids or n−3 fatty acids,[1] are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure.[2] They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology.[2][3] The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids.[4] DHA and EPA accumulate in fish that eat these algae.[5] Common sources of plant oils containing ALA include walnuts, edible seeds, and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils,[1] and algae oil.

Mammals are unable to synthesize the essential omega−3 fatty acid ALA and can only obtain it through diet. However, they can use ALA, when available, to form EPA and DHA, by creating additional double bonds along its carbon chain (desaturation) and extending it (elongation). Namely, ALA (18 carbons and 3 double bonds) is used to make EPA (20 carbons and 5 double bonds), which is then used to make DHA (22 carbons and 6 double bonds).[1][2] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[6] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[2][7]

There is no high-quality evidence that dietary supplementation with omega−3 fatty acids reduces the risk of cancer or cardiovascular disease.[8][9][10] Fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[11][12][13]

History

[edit]

In 1929, George and Mildred Burr discovered that fatty acids were critical to health. If fatty acids were absent from the diet, a life-threatening deficiency syndrome ensued. The Burrs coined the phrase "essential fatty acids".[14] Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes.[15] Subsequently, awareness of the health benefits of essential fatty acids has dramatically increased since the 1980s.[16]

On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega−3 fatty acids, stating, "supportive but not conclusive research shows that consumption of EPA and DHA [omega−3] fatty acids may reduce the risk of coronary heart disease".[17] This updated and modified their health risk advice letter of 2001 (see below).

The Canadian Food Inspection Agency has recognized the importance of DHA omega−3 and permits the following claim for DHA: "DHA, an omega−3 fatty acid, supports the normal physical development of the brain, eyes, and nerves primarily in children under two years of age."[18]

Historically, whole food diets contained sufficient amounts of omega−3, but because omega−3 is readily oxidized, the trend toward shelf-stable processed foods has led to a deficiency in omega−3 in manufactured foods.[19]

Nomenclature

[edit]
Chemical structure of α-linolenic acid (ALA), a fatty acid with a chain of 18 carbons with three double bonds on carbons numbered 9, 12, and 15. The omega (ω) end of the chain is at carbon 18, and the double bond closest to the omega carbon begins at carbon 15 = 18−3. Hence, ALA is a ω−3 fatty acid with ω = 18.

The terms ω−3 ("omega−3") fatty acid and n−3 fatty acid are derived from the nomenclature of organic chemistry.[2][20] One way in which an unsaturated fatty acid is named is determined by the location, in its carbon chain, of the double bond which is closest to the methyl end of the molecule.[20] In general terminology, n (or ω) represents the locant of the methyl end of the molecule, while the number n−x (or ω−x) refers to the locant of its nearest double bond. Thus, in omega3 fatty acids in particular, there is a double bond located at the carbon numbered 3, starting from the methyl end of the fatty acid chain. This classification scheme is useful since most chemical changes occur at the carboxyl end of the molecule, while the methyl group and its nearest double bond are unchanged in most chemical or enzymatic reactions.

In the expressions n−x or ω−x, the symbol is a minus sign rather than a hyphen (or dash), although it is never read as such. Also, the symbol n (or ω) represents the locant of the methyl end, counted from the carboxyl end of the fatty acid carbon chain. For instance, in an omega−3 fatty acid with 18 carbon atoms (see illustration), where the methyl end is at location 18 from the carboxyl end, n (or ω) represents the number 18, and the notation n−3 (or ω−3) represents the subtraction 18−3 = 15, where 15 is the locant of the double bond which is closest to the methyl end, counted from the carboxyl end of the chain.[20]

Although n and ω (omega) are synonymous, the IUPAC recommends that n be used to identify the highest carbon number of a fatty acid.[20] Nevertheless, the more common name – omega3 fatty acid – is used in both the lay media and scientific literature.

Example

[edit]

For example, α-linolenic acid (ALA; illustration) is an 18-carbon chain having three double bonds, the first being located at the third carbon from the methyl end of the fatty acid chain. Hence, it is an omega3 fatty acid. Counting from the other end of the chain, that is the carboxyl end, the three double bonds are located at carbons 9, 12, and 15. These three locants are typically indicated as Δ9c, Δ12c, Δ15c, or cisΔ9, cisΔ12, cisΔ15, or cis-cis-cis-Δ9,12,15, where c or cis means that the double bonds have a cis configuration.

α-Linolenic acid is polyunsaturated (containing more than one double bond) and is also described by a lipid number, 18:3, meaning that there are 18 carbon atoms and 3 double bonds.[20]

Chemistry

[edit]
Chemical structure of eicosapentaenoic acid (EPA)
Chemical structure of docosahexaenoic acid (DHA)

An omega−3 fatty acid is a fatty acid with multiple double bonds, where the first double bond is between the third and fourth carbon atoms from the end of the carbon atom chain. "Short-chain" omega−3 fatty acids have a chain of 18 carbon atoms or less, while "long-chain" omega−3 fatty acids have a chain of 20 or more.

Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaenoic acid (22:6, n-3; DHA).[21] These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges (-CH
2
-), so that there are two single bonds between each pair of adjacent double bonds.

The atoms at bis-allylic (between double bonds) sites are prone to oxidation by free radicals. Replacement of hydrogen atoms with deuterium atoms in this location protects the omega-3 fatty acid from lipid peroxidation and ferroptosis.[22]

List of omega−3 fatty acids

[edit]

This table lists several different names for the most common omega−3 fatty acids found in nature.

Common name Lipid number Chemical name
Hexadecatrienoic acid (HTA) 16:3 (n−3) all-cis-7,10,13-hexadecatrienoic acid
α-Linolenic acid (ALA) 18:3 (n−3) all-cis-9,12,15-octadecatrienoic acid
Stearidonic acid (SDA) 18:4 (n−3) all-cis-6,9,12,15-octadecatetraenoic acid
Eicosatrienoic acid (ETE) 20:3 (n−3) all-cis-11,14,17-eicosatrienoic acid
Eicosatetraenoic acid (ETA) 20:4 (n−3) all-cis-8,11,14,17-eicosatetraenoic acid
Eicosapentaenoic acid (EPA) 20:5 (n−3) all-cis-5,8,11,14,17-eicosapentaenoic acid
Heneicosapentaenoic acid (HPA) 21:5 (n−3) all-cis-6,9,12,15,18-heneicosapentaenoic acid
Docosapentaenoic acid (DPA),
Clupanodonic acid
22:5 (n−3) all-cis-7,10,13,16,19-docosapentaenoic acid
Docosahexaenoic acid (DHA) 22:6 (n−3) all-cis-4,7,10,13,16,19-docosahexaenoic acid
Tetracosapentaenoic acid 24:5 (n−3) all-cis-9,12,15,18,21-tetracosapentaenoic acid
Tetracosahexaenoic acid (Nisinic acid) 24:6 (n−3) all-cis-6,9,12,15,18,21-tetracosahexaenoic acid

Forms

[edit]

Omega−3 fatty acids occur naturally in two forms, triglycerides and phospholipids. In the triglycerides, they, together with other fatty acids, are bonded to glycerol; three fatty acids are attached to glycerol. Phospholipid omega−3 is composed of two fatty acids attached to a phosphate group via glycerol.

The triglycerides can be converted to the free fatty acid or to methyl or ethyl esters, and the individual esters of omega−3 fatty acids are available.[clarification needed]

Mechanism of action

[edit]

The 'essential' fatty acids were given their name when researchers found that they are essential to normal growth in young children and animals. The omega−3 fatty acid DHA, also known as docosahexaenoic acid, is found in high abundance in the human brain.[23] It is produced by a desaturation process, but humans lack the desaturase enzyme, which acts to insert double bonds at the ω6 and ω3 position.[23] Therefore, the ω6 and ω3 polyunsaturated fatty acids cannot be synthesized, are appropriately called essential fatty acids, and must be obtained from the diet.[23]

In 1964, it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent, prostaglandin E2,[24] which is involved in the immune response of traumatized and infected tissues.[25] By 1979, eicosanoids were further identified, including thromboxanes, prostacyclins, and leukotrienes.[25] The eicosanoids typically have a short period of activity in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects.[25] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids and docosanoids,[26] but at a slower rate. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[25] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[25]

Interconversion

[edit]

Conversion efficiency of ALA to EPA and DHA

[edit]

Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[27][28] The omega−3 conversion efficiency is greater in women than in men, but less studied.[29] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[30]

These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[31] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[32] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[33]

The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.[2][34] Women have higher ALA-to-DHA conversion efficiency than men, which is presumed[35] to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.[36]

Omega−6 to omega−3 ratio

[edit]

Human diet has changed rapidly in recent centuries resulting in a reported increased diet of omega−6 in comparison to omega−3.[37] The rapid evolution of human diet away from a 1:1 omega−3 and omega−6 ratio, such as during the Neolithic Agricultural Revolution, has presumably been too fast for humans to have adapted to biological profiles adept at balancing omega−3 and omega−6 ratios of 1:1.[38] This is commonly believed to be the reason why modern diets are correlated with many inflammatory disorders.[37] While omega−3 polyunsaturated fatty acids may be beneficial in preventing heart disease in humans, the level of omega−6 polyunsaturated fatty acids (and, therefore, the ratio) does not matter.[33][39]

Both omega−6 and omega−3 fatty acids are essential: humans must consume them in their diet. Omega−6 and omega−3 eighteen-carbon polyunsaturated fatty acids compete for the same metabolic enzymes, thus the omega−6:omega−3 ratio of ingested fatty acids has significant influence on the ratio and rate of production of eicosanoids, a group of hormones intimately involved in the body's inflammatory and homeostatic processes, which include the prostaglandins, leukotrienes, and thromboxanes, among others. Altering this ratio can change the body's metabolic and inflammatory state.[40]

Metabolites of omega−6 are more inflammatory (esp. arachidonic acid) than those of omega−3. However, in terms of heart health omega-6 fatty acids are less harmful than they are presumed to be. A meta-analysis of six randomized trials found that replacing saturated fat with omega-6 fats reduced the risk of coronary events by 24%.[41]

A healthy ratio of omega-6 to omega-3 is needed; healthy ratios, according to some authors, range from 1:1 to 1:4.[42] Other authors believe that a ratio of 4:1 (4 times as much omega−6 as omega−3) is already healthy.[43][44]

Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3).[45] The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1,[46] soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3,[47] cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.[48]

Biochemistry

[edit]

Transporters

[edit]

DHA in the form of lysophosphatidylcholine is transported into the brain by a membrane transport protein, MFSD2A, which is exclusively expressed in the endothelium of the blood–brain barrier.[49][50]

Dietary sources

[edit]
Grams of omega−3 per 3oz (85g) serving[51]
Common name grams omega−3
Herring, sardines 1.3–2
Mackerel: Spanish/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[52]
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
Red snapper 0.29
Shark 0.83
King mackerel 0.36
Hoki (blue grenadier) 0.41[52]
Gemfish 0.40[52]
Blue eye cod 0.31[52]
Sydney rock oysters 0.30[52]
Tuna, canned 0.23[52]
Snapper 0.22[52]
Eggs, large regular 0.109[52]
Strawberry or Kiwifruit 0.10–0.20
Broccoli 0.10–0.20
Barramundi, saltwater 0.100[52]
Giant tiger prawn 0.100[52]
Lean red meat 0.031[52]
Turkey 0.030[52]
Milk, regular 0.00[52]

Dietary recommendations

[edit]

In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.[53] The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."[citation needed] As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids,[53] although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.[1]

The European Commission sponsored a working group to develop recommendations on dietary fat intake in pregnancy and lactation. In 2008, the working group published consensus recommendations,[54] including the following:

  • "pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA/day"
  • "women of childbearing age should aim to consume one to two portions of sea fish per week, including oily fish"
  • "intake of the DHA precursor, α-linolenic acid, is far less effective with regard to DHA deposition in fetal brain than preformed DHA"

However, the seafood supply to meet these recommendations is currently too low in most European countries and if met would be unsustainable.[55]

In the EU, the EFSA publishes the Dietary Reference Values (DRVs), recommending Adequate Intake values for EPA+DHA and DHA:[56]

Dietary Reference Values (DRVs) for EPA+DHA and DHA
Age group (years) EPA+DHA (mg/day)1 DHA (mg/day)1
7–11 months2 100
1 100
2-3 250
4-6 250
7-10 250
11-14 250
15-17 250
≥18 250
Pregnancy 250 + 100—2003
Lactation 250 + 100—2003
^1 AI, Adequate Intake
^2 i.e. the second half of the first year of life (from the beginning of the 7th month to the 1st birthday)
^3 in addition to combined intakes of EPA and DHA of 250 mg/day

The American Heart Association (AHA) has made recommendations for EPA and DHA due to their cardiovascular benefits: individuals with no history of coronary heart disease or myocardial infarction should consume oily fish two times per week; and "Treatment is reasonable" for those having been diagnosed with coronary heart disease. For the latter the AHA does not recommend a specific amount of EPA + DHA, although it notes that most trials were at or close to 1000 mg/day. The benefit appears to be on the order of a 9% decrease in relative risk.[57] The European Food Safety Authority (EFSA) approved a claim "EPA and DHA contributes to the normal function of the heart" for products that contain at least 250 mg EPA + DHA. The report did not address the issue of people with pre-existing heart disease. The World Health Organization recommends regular fish consumption (1-2 servings per week, equivalent to 200 to 500 mg/day EPA + DHA) as protective against coronary heart disease and ischaemic stroke.

Contamination

[edit]

Heavy metal poisoning from consuming fish oil supplements is highly unlikely, because heavy metals (mercury, lead, nickel, arsenic, and cadmium) selectively bind with protein in the fish flesh rather than accumulate in the oil.[58][59]

However, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[60]

Throughout their history, the Council for Responsible Nutrition and the World Health Organization have published acceptability standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard.[61][non-primary source needed] Fish oils that are molecularly distilled under vacuum typically make this highest-grade; levels of contaminants are stated in parts per billion per trillion.[citation needed][62]

Rancidity

[edit]

A 2022 study found that a number of products on the market used oxidised oils, with the rancidity often masked by flavourings. Another study in 2015 found that an average of 20% of products had excess oxidation. Whether rancid fish oil is harmful remains unclear. Some studies show that highly oxidised fish oil can have a negative impact on cholesterol levels. Animal testing showed that high doses have toxic effects. Furthermore, rancid oil is likely to be less effective than fresh fish oil.[63][64]

Fish

[edit]

The most widely available dietary source of EPA and DHA is oily fish, such as salmon, herring, mackerel, anchovies, and sardines.[1] Oils from these fishes have around seven times as much omega−3 as omega−6. Other oily fish, such as tuna, also contain n-3 in somewhat lesser amounts.[1][65] Although fish are a dietary source of omega−3 fatty acids, fish do not synthesize omega−3 fatty acids, but rather obtain them via their food supply, including algae or plankton.[66]

In order for farmed marine fish to have amounts of EPA and DHA comparable to those of wild-caught fish, their feed must be supplemented with EPA and DHA, most commonly in the form of fish oil. For this reason, 81% of the global fish oil supply in 2009 was consumed by aquaculture.[5] By 2019, two alternative sources of EPA and DHA for fish have been partially commercialized: genetically modified canola oil and Schizochytrium algal oil.[67]

Fish oil

[edit]
Fish oil capsules

Marine and freshwater fish oil vary in content of arachidonic acid, EPA and DHA.[68] They also differ in their effects on organ lipids.[68]

Not all forms of fish oil may be equally digestible. Of four studies that compare bioavailability of the glyceryl ester form of fish oil vs. the ethyl ester form, two have concluded the natural glyceryl ester form is better, and the other two studies did not find a significant difference. No studies have shown the ethyl ester form to be superior, although it is cheaper to manufacture.[69][70]

Krill

[edit]
Krill oil capsules

Krill oil is a source of omega−3 fatty acids.[71] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[72] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[73][74][75] Preliminary studies indicate that the DHA and EPA omega−3 fatty acids found in krill oil are more bio-available than in fish oil.[76] Additionally, krill oil contains astaxanthin, a marine-source keto-carotenoid antioxidant that may act synergistically with EPA and DHA.[77][78][79][80][12]

Plant sources

[edit]
Chia is grown commercially for its seeds rich in ALA
Flax seeds contain linseed oil which has high ALA content
Capsules of omega-3 oil derived from marine algae (Schizochytrium sp.), 96.3% of total content
Table 1. ALA content as the percentage of the seed oil.[81]
Common name Alternative name Linnaean name % ALA
kiwifruit (fruit) Chinese gooseberry Actinidia deliciosa 63[82]
perilla shiso Perilla frutescens 61
chia chia sage Salvia hispanica 58
linseed flax Linum usitatissimum 53[37] – 59[83]
lingonberry cowberry Vaccinium vitis-idaea 49
fig common fig Ficus carica 47.7[84]
camelina gold-of-pleasure Camelina sativa 36
purslane portulaca Portulaca oleracea 35
black raspberry Rubus occidentalis 33
hempseed Cannabis sativa 19
canola rapeseed mostly Brassica napus 9[37] – 11
Table 2. ALA content as the percentage of the whole food.[37][85]
Common name Linnaean name % ALA
linseed Linum usitatissimum 18.1
hempseed Cannabis sativa 8.7
butternut Juglans cinerea 8.7
Persian walnut Juglans regia 6.3
pecan Carya illinoinensis 0.6
hazelnut Corylus avellana 0.1

Linseed (or flaxseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.[86] A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.[87]

The longer-chain EPA and DHA are only naturally made by marine algae and phytoplankton.[4][5] The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA, but not EPA, and can be produced commercially in bioreactors for use as food additives.[88] Oil from brown algae (kelp) is a source of EPA.[89] The alga Nannochloropsis also has high levels of EPA.[90]

Some transgenic initiatives have transferred the ability to make EPA and DHA into existing high-yielding crop species of land plants:[91]

  • Camelina sativa: In 2013, Rothamsted Research reported two genetically modified forms of this plant. Oil from the seeds of this plant contained on average 15% ALA, 11% EPA, and 8% DHA in one development and 11% ALA and 24% EPA in another.[92][93]
  • Canola: In 2011, CSIRO, GRDC, and Nufarm developed a version of canola that produces DHA in seeds; the oil contains 10% DHA and almost no EPA. In 2018, it was approved as an animal feed additive in Australia.[94] In 2021, the US FDA acknowledged it as a New Dietary Ingredient for humans.[95] Separately, Cargill has commercialized a different strain of canola that produces EPA and DHA for fish feed. The oil contains 8.1% EPA and 0.8% DHA.[91]

Eggs

[edit]

Eggs produced by hens fed a diet of greens and insects contain higher levels of omega−3 fatty acids than those produced by chickens fed corn or soybeans.[96] In addition to feeding chickens insects and greens, fish oils may be added to their diets to increase the omega−3 fatty acid concentrations in eggs.[97]

The addition of flax and canola seeds, both good sources of alpha-linolenic acid, to the diets of laying chickens, increases the omega−3 content of the eggs, predominantly DHA.[98] However, this enrichment could lead to an increment of lipid oxidation in the eggs if the seeds are used in higher doses, without using an appropriate antioxidant.[99]

The addition of green algae or seaweed to the diets boosts the content of DHA and EPA, which are the forms of omega−3 approved by the FDA for medical claims. A common consumer complaint is "Omega−3 eggs can sometimes have a fishy taste if the hens are fed marine oils".[100]

Meat

[edit]

Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the sources of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass-fed animals.[101] When cattle are taken off omega−3 fatty acid-rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[102]

The omega−6:omega−3 ratio of grass-fed beef is about 2:1, making it a more useful source of omega−3 than grain-fed beef, which usually has a ratio of 4:1.[103]

In a 2009 joint study by the USDA and researchers at Clemson University in South Carolina, grass-fed beef was compared with grain-finished beef. The researchers found that grass-finished beef is higher in moisture content, 42.5% lower total lipid content, 54% lower in total fatty acids, 54% higher in beta-carotene, 288% higher in vitamin E (alpha-tocopherol), higher in the B-vitamins thiamin and riboflavin, higher in the minerals calcium, magnesium, and potassium, 193% higher in total omega−3s, 117% higher in CLA (cis-9, trans-11 octadecenoic acid, a conjugated linoleic acid, which is a potential cancer fighter), 90% higher in vaccenic acid (which can be transformed into CLA), lower in the saturated fats, and has a healthier ratio of omega−6 to omega−3 fatty acids (1.65 vs 4.84). Protein and cholesterol content were equal.[103]

The omega−3 content of chicken meat may be enhanced by increasing the animals' dietary intake of grains high in omega−3, such as flax, chia, and canola.[104]

Kangaroo meat is also a source of omega−3, with fillet and steak containing 74 mg per 100 g of raw meat.[105]

Seal oil

[edit]

Seal oil is a source of EPA, DPA, and DHA, and is commonly used in Arctic regions. According to Health Canada, it helps to support the development of the brain, eyes, and nerves in children up to 12 years of age.[106] Like all seal products, it is not allowed to be imported into the European Union.[107]

A Canadian company, FeelGood Natural Health, pleaded guilty in 2023 to illegally selling seal oil capsules to American consumers. The company sold over 900 bottles of the capsules, worth over $10,000. Seal oil is made from the blubber of dead seals, and is illegal to sell in the United States under the Marine Mammal Protection Act. The global population of harp seals stands at around 7 million, and they have been hunted in Canada for thousands of years. FeelGood was sentenced to pay a fine of $20,000 and three years of probation.[108]

Other sources

[edit]

A trend in the early 21st century was to fortify food with omega−3 fatty acids.[88][109]

Health effects of omega-3 supplementation

[edit]

The association between supplementation and a lower risk of all-cause mortality is inconclusive.[11][110]

Cancer

[edit]

There is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.[1][9][40][111] Omega-3 supplements do not improve body weight, muscle maintenance or quality of life in cancer patients.[112]

Cardiovascular disease

[edit]

Moderate and high quality evidence from a 2020 review showed that EPA and DHA, such as that found in omega−3 polyunsaturated fatty acid supplements, does not appear to improve mortality or cardiovascular health.[8] There is weak evidence indicating that α-linolenic acid may be associated with a small reduction in the risk of a cardiovascular event or the risk of arrhythmia.[2][8]

A 2018 meta-analysis found no support that daily intake of one gram of omega−3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.[11] However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.[113] No protective effect against the development of stroke or all-cause mortality was seen in this population.[113] A 2021 meta-analysis found that supplementation was associated with a reduced risk of myocardial infarction and coronary heart disease.[114]

Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.[115] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[12] In the EU, a review by the European Medicines Agency of omega−3 fatty acid medicines containing a combination of an ethyl ester of eicosapentaenoic acid and docosahexaenoic acid at a dose of 1 g per day concluded that these medicines are not effective in secondary prevention of heart problems in people who have had a myocardial infarction.[116]

Evidence suggests that omega−3 fatty acids modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure.[117][118] Omega−3 fatty acids can also reduce heart rate,[119] an emerging risk factor. Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation. Omega−3 fatty acids reduce blood triglyceride levels, but do not significantly change the level of LDL cholesterol or HDL cholesterol.[120][121] The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5–1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1–2 g/day; and >500 mg/dL be treated under a physician's supervision with 2–4 g/day using a prescription product.[122] In this population, omega−3 fatty acid supplementation decreases the risk of heart disease by about 25%.[123]

A 2019 review found that omega-3 fatty acid supplements make little or no difference to cardiovascular mortality and that people with myocardial infarction have no benefit in taking the supplements.[124] A 2021 review found that omega-3 supplementation did not affect cardiovascular disease outcomes.[10]

A 2021 review concluded that use of omega-3 supplements was associated with an increased risk of atrial fibrillation in people having high blood triglycerides.[125] A meta-analysis showed that use of marine omega-3 supplementation was associated with an increased risk of atrial fibrillation, with the risk appearing to increase for doses greater than one gram per day.[126]

Chronic kidney disease

[edit]

In people with chronic kidney disease (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.[127] There was also moderate certainty that supplementation did not prevent hospitalisation or death within a 12-month period.[127]

Stroke

[edit]

A 2022 Cochrane review of controlled trials did not find clear evidence that marine-derived omega-3 supplementation improves cognitive and physical recovery or social, and emotional wellbeing following stroke diagnosis, nor prevents stroke recurrence and mortality.[13] In this review, mood appeared to worsen slightly among those receiving 3g fish oil supplementation for 12 weeks; psychometric scores changed by 1.41 (0.07 to 2.75) points less than those receiving palm and soy oil.[13] However, this represented only a single small study and was not observed in a study lasting more than 3 months. Overall, the review was limited by the low number of high-quality evidence available.

Inflammation

[edit]

A 2013 systematic review found tentative evidence of benefit for lowering inflammation levels in healthy adults and in people with one or more biomarkers of metabolic syndrome.[128] Consumption of omega−3 fatty acids from marine sources lowers blood markers of inflammation such as C-reactive protein, interleukin 6, and TNF alpha.[129][130][131]

For rheumatoid arthritis, one systematic review found consistent but modest evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs.[132] The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels.[133] The National Center for Complementary and Integrative Health has concluded that "supplements containing omega−3 fatty acids ... may help relieve rheumatoid arthritis symptoms" but warns that such supplements "may interact with drugs that affect blood clotting".[134]

Developmental disabilities

[edit]

One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[135] A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",[136] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[137] Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.[138]

A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[139] A 2018 Cochrane systematic review with moderate to high quality of evidence suggested that omega−3 fatty acids may reduce risk of perinatal death, risk of low body weight babies; and possibly mildly increased LGA babies.[140]

A 2021 umbrella review with moderate to high quality of evidence suggested that "omega-3 supplementation during pregnancy can exert favorable effects against pre-eclampsia, low-birth weight, pre-term delivery, and post-partum depression, and can improve anthropometric measures, immune system, and visual activity in infants and cardiometabolic risk factors in pregnant mothers."[141]

Mental health

[edit]

Omega-3 supplementation has not been shown to significantly affect symptoms of anxiety, major depressive disorder or schizophrenia.[142][143] A 2021 Cochrane review concluded that there is not "sufficient high‐certainty evidence to determine the effects of n‐3PUFAs as a treatment for MDD".[144] Omega−3 fatty acids have also been investigated as an add-on for the treatment of depression associated with bipolar disorder although there is limited data available.[145] Two reviews have suggested that omega-3 fatty acid supplementation significantly improves depressive symptoms in perinatal women.[141][146]

A 2015 study concluded that there are multiple factors responsible for depression and deficiency of omega 3 fatty acids can be one of them. It further stated that only those patients who have depression due to insufficient omega-3 fatty acids can respond well to the omega 3 supplements while others are unlikely to get any positive effects.[147] Meta-analysis suggest that supplements with higher concentration of EPA than DHA are more likely to act as anti-depressants.[148][149]

In contrast to dietary supplementation studies, there is significant difficulty in interpreting the literature regarding dietary intake of omega−3 fatty acids (e.g. from fish) due to participant recall and systematic differences in diets.[150] There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.[151][152] A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.[152]

Cognitive aging

[edit]

A 2016 Cochrane review found no convincing evidence for the use of omega‐3 PUFA supplements in treatment of Alzheimer's disease or dementia.[153] There is preliminary evidence of effect on mild cognitive problems, but none supporting an effect in healthy people or those with dementia.[154][155] A 2020 review suggested that omega 3 supplementation has no effect on global cognitive function but has a mild benefit in improving memory in non-demented adults.[156]

A 2022 review found promising evidence for prevention of cognitive decline in people who regularly eat long-chain omega 3 rich foods. Conversely, clinical trials with participants already diagnosed with Alzheimer's show no effect.[157] A 2020 review concluded that long-chain omega-3 supplements do not deter cognitive decline in older adults.[158]

Brain and visual functions

[edit]

Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[159][160] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[161][162] Omega 3 PUFA supplementation has no effect on macular degeneration or development of visual loss.[163]

Atopic diseases

[edit]

Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis, and allergic asthma) are controversial; therefore, as of 2013 it could not be stated either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in the context of atopic diseases.[164]

Phenylketonuria

[edit]

People with PKU often have low intake of omega−3 fatty acids, because nutrients rich in omega−3 fatty acids are excluded from their diet due to high protein content.[165]

Asthma

[edit]

As of 2015, there was no evidence that taking omega−3 supplements can prevent asthma attacks in children.[166]

Diabetes

[edit]

A 2019 review found that omega-3 supplements have no effect on prevention and treatment of type 2 diabetes.[167][168] A 2021 meta-analysis found that supplementation with omega-3 had positive effects on diabetes biomarkers, such as fasting blood glucose and insulin resistance.[169]

Sexual health

[edit]

A 2017 animal study examined the effects of Omega-3 supplement on BPF-induced erectile dysfunction. Rats in the treatment group were found to have significantly improved erection quality.[170]

See also

[edit]

Notes

[edit]

References

[edit]
  1. ^ a b c d e f g "Omega−3 Fatty Acids". Office of Dietary Supplements, US National Institutes of Health. 26 March 2021. Archived from the original on 8 December 2016. Retrieved 10 June 2021.
  2. ^ a b c d e f g "Essential Fatty Acids". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 1 May 2019. Archived from the original on 17 April 2015. Retrieved 10 June 2021.
  3. ^ Scorletti E, Byrne CD (2013). "Omega−3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease". Annual Review of Nutrition. 33 (1): 231–248. doi:10.1146/annurev-nutr-071812-161230. PMID 23862644.
  4. ^ a b Jacobsen C, Nielsen NS, Horn AF, Sørensen AD (31 July 2013). Food Enrichment with Omega-3 Fatty Acids. Elsevier. p. 391. ISBN 978-0-85709-886-3. Archived from the original on 18 September 2023. Retrieved 5 February 2022.
  5. ^ a b c "Farmed fish: a major provider or a major consumer of omega-3 oils?| GLOBEFISH |". Food and Agriculture Organization of the United Nations. Archived from the original on 3 February 2022. Retrieved 4 February 2022.
  6. ^ Freemantle E, Vandal M, Tremblay-Mercier J, Tremblay S, Blachère JC, Bégin ME, et al. (September 2006). "Omega-3 fatty acids, energy substrates, and brain function during aging". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 75 (3): 213–220. doi:10.1016/j.plefa.2006.05.011. PMID 16829066.
  7. ^ Chaiyasit W, Elias RJ, McClements DJ, Decker EA (2007). "Role of physical structures in bulk oils on lipid oxidation". Critical Reviews in Food Science and Nutrition. 47 (3): 299–317. doi:10.1080/10408390600754248. PMID 17453926. S2CID 10190504.
  8. ^ a b c Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. (February 2020). "Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease". The Cochrane Database of Systematic Reviews. 2020 (3): CD003177. doi:10.1002/14651858.CD003177.pub5. PMC 7049091. PMID 32114706.
  9. ^ a b Zhang YF, Gao HF, Hou AJ, Zhou YH (2014). "Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials". BMC Public Health. 14: 204. doi:10.1186/1471-2458-14-204. PMC 3938028. PMID 24568238.
  10. ^ a b Rizos, Evangelos C; Markozannes, Georgios; Tsapas, Apostolos; Mantzoros, Christos S; Ntzani, Evangelia E (January 2021). "Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis". Heart. 107 (2): 150–158. doi:10.1136/heartjnl-2020-316780. PMID 32820013.
  11. ^ a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–234. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.
  12. ^ a b c Grey A, Bolland M (March 2014). "Clinical trial evidence and use of fish oil supplements". JAMA Internal Medicine. 174 (3): 460–2. doi:10.1001/jamainternmed.2013.12765. PMID 24352849.
  13. ^ a b c Alvarez Campano CG, Macleod MJ, Aucott L, Thies F (June 2022). "Marine-derived n-3 fatty acids therapy for stroke". The Cochrane Database of Systematic Reviews. 2022 (6): CD012815. doi:10.1002/14651858.CD012815.pub3. PMC 9241930. PMID 35766825.
  14. ^ Mukhopadhyay R (October 2012). "Essential fatty acids: the work of George and Mildred Burr". The Journal of Biological Chemistry. 287 (42): 35439–35441. doi:10.1074/jbc.O112.000005. PMC 3471758. PMID 23066112.
  15. ^ Caramia G (April 2008). "[The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy]". Minerva Pediatrica. 60 (2): 219–233. PMID 18449139. Archived from the original on 2022-08-19. Retrieved 2022-04-08.
  16. ^ Holman RT (February 1998). "The slow discovery of the importance of omega 3 essential fatty acids in human health". The Journal of Nutrition. 128 (2 Suppl): 427S–433S. doi:10.1093/jn/128.2.427S. PMID 9478042.
  17. ^ "FDA announces qualified health claims for omega−3 fatty acids" (Press release). United States Food and Drug Administration. September 8, 2004. Retrieved 2006-07-10.
  18. ^ Canadian Food Inspection Agency. Acceptable nutrient function claims Archived 2018-12-04 at the Wayback Machine. Accessed 30 April 2015
  19. ^ Simopoulos AP (March 2016). "An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity". Nutrients. 8 (3): 128. doi:10.3390/nu8030128. PMC 4808858. PMID 26950145.
  20. ^ a b c d e Ratnayake WM, Galli C (2009). "Fat and fatty acid terminology, methods of analysis and fat digestion and metabolism: a background review paper". Annals of Nutrition & Metabolism. 55 (1–3): 8–43. doi:10.1159/000228994. PMID 19752534.
  21. ^ "Omega−3 Fatty Acids: An Essential Contribution". TH Chan School of Public Health, Harvard University, Boston. 2017. Archived from the original on 2018-12-31. Retrieved 2018-12-31.
  22. ^ Demidov, Vadim V. (1 April 2020). "Site-specifically deuterated essential lipids as new drugs against neuronal, retinal and vascular degeneration". Drug Discovery Today. 25 (8): 1469–1476. doi:10.1016/j.drudis.2020.03.014. PMID 32247036. S2CID 214794450.
  23. ^ a b c van West D, Maes M (February 2003). "Polyunsaturated fatty acids in depression". Acta Neuropsychiatrica. 15 (1): 15–21. doi:10.1034/j.1601-5215.2003.00004.x. PMID 26984701. S2CID 5343605.
  24. ^ Bergström, Sune; Danielsson, Henry; Klenberg, Dorrit; Samuelsson, Bengt (November 1964). "The Enzymatic Conversion of Essential Fatty Acids into Prostaglandins". Journal of Biological Chemistry. 239 (11): PC4006–PC4008. doi:10.1016/S0021-9258(18)91234-2.
  25. ^ a b c d e Lands WE (May 1992). "Biochemistry and physiology of n-3 fatty acids". FASEB Journal. 6 (8): 2530–6. doi:10.1096/fasebj.6.8.1592205. PMID 1592205. S2CID 24182617.
  26. ^ Kuda O (May 2017). "Bioactive metabolites of docosahexaenoic acid". Biochimie. 136: 12–20. doi:10.1016/j.biochi.2017.01.002. PMID 28087294.
  27. ^ Gerster H (1998). "Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?". International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift für Vitamin- und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition. 68 (3): 159–73. PMID 9637947.
  28. ^ Brenna JT (March 2002). "Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man". Current Opinion in Clinical Nutrition and Metabolic Care. 5 (2): 127–32. doi:10.1097/00075197-200203000-00002. PMID 11844977.
  29. ^ Burdge GC, Calder PC (September 2005). "Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults". Reproduction, Nutrition, Development. 45 (5): 581–97. doi:10.1051/rnd:2005047. PMID 16188209.
  30. ^ Lohner S, Fekete K, Marosvölgyi T, Decsi T (2013). "Gender differences in the long-chain polyunsaturated fatty acid status: systematic review of 51 publications". Annals of Nutrition & Metabolism. 62 (2): 98–112. doi:10.1159/000345599. PMID 23327902.
  31. ^ Ruxton CH, Calder PC, Reed SC, Simpson MJ (June 2005). "The impact of long-chain n-3 polyunsaturated fatty acids on human health". Nutrition Research Reviews. 18 (1): 113–29. doi:10.1079/nrr200497. PMID 19079899.
  32. ^ Simopoulos AP (June 2008). "The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases". Experimental Biology and Medicine. 233 (6): 674–88. doi:10.3181/0711-MR-311. PMID 18408140. S2CID 9044197.
  33. ^ a b Griffin BA (February 2008). "How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study". Current Opinion in Lipidology. 19 (1): 57–62. doi:10.1097/MOL.0b013e3282f2e2a8. PMID 18196988. S2CID 13058827.
  34. ^ "Conversion Efficiency of ALA to DHA in Humans". Archived from the original on 5 August 2010. Retrieved 21 October 2007.
  35. ^ "Women have better ALA conversion efficiency". DHA EPA omega−3 Institute. Archived from the original on 5 July 2015. Retrieved 21 July 2015.
  36. ^ Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP (July 2006). "Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio". The American Journal of Clinical Nutrition. 84 (1): 44–53. doi:10.1093/ajcn/84.1.44. PMID 16825680.
  37. ^ a b c d e DeFilippis, Andrew P.; Sperling, Laurence S. (March 2006). "Understanding omega-3's". American Heart Journal. 151 (3): 564–570. doi:10.1016/j.ahj.2005.03.051. PMID 16504616.
  38. ^ Hofmeijer-Sevink MK, Batelaan NM, van Megen HJ, Penninx BW, Cath DC, van den Hout MA, van Balkom AJ (March 2012). "Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands Study of Depression and Anxiety (NESDA)". Journal of Affective Disorders. 137 (1–3): 106–12. doi:10.1016/j.jad.2011.12.008. PMID 22240085.
  39. ^ Willett WC (September 2007). "The role of dietary n-6 fatty acids in the prevention of cardiovascular disease". Journal of Cardiovascular Medicine. 8 (Suppl 1): S42-45. doi:10.2459/01.JCM.0000289275.72556.13. PMID 17876199. S2CID 1420490.
  40. ^ a b Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al. (April 2006). "Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ. 332 (7544): 752–760. doi:10.1136/bmj.38755.366331.2F. PMC 1420708. PMID 16565093.
  41. ^ "No need to avoid healthy omega-6 fats". May 2009. Archived from the original on 2022-05-23. Retrieved 2022-05-23.
  42. ^ Lands WE (2005). Fish, omega−3 and human health. American Oil Chemists' Society. ISBN 978-1-893997-81-3.
  43. ^ Simopoulos AP (October 2002). "The importance of the ratio of omega-6/omega-3 essential fatty acids". Biomedicine & Pharmacotherapy. 56 (8): 365–79. doi:10.1016/S0753-3322(02)00253-6. PMID 12442909.
  44. ^ Daley CA, Abbott A, Doyle P, Nader G, Larson S (2004). "A literature review of the value-added nutrients found in grass-fed beef products". California State University, Chico College of Agriculture. Archived from the original on 2008-07-06. Retrieved 2008-03-23.
  45. ^ Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE (June 2006). "Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity". The American Journal of Clinical Nutrition. 83 (6 Suppl): 1483S–1493S. doi:10.1093/ajcn/83.6.1483S. PMID 16841858.
  46. ^ Martina Bavec; Franc Bavec (2006). Organic Production and Use of Alternative Crops. London: Taylor & Francis Ltd. p. 178. ISBN 978-1-4200-1742-7. Retrieved 2013-02-18.
  47. ^ Erasmus, Udo, Fats and Oils. 1986. Alive books, Vancouver, ISBN 0-920470-16-5 p. 263 (round-number ratio within ranges given.)
  48. ^ "Oil, vegetable, corn, industrial and retail, all purpose salad or cooking; USDA Nutrient Data, SR-21". Conde Nast. Archived from the original on 13 February 2019. Retrieved 12 April 2014.
  49. ^ "Sodium-dependent lysophosphatidylcholine symporter 1". UniProt. Archived from the original on 22 April 2019. Retrieved 2 April 2016.
  50. ^ Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, et al. (May 2014). "Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid". Nature. 509 (7501): 503–6. Bibcode:2014Natur.509..503N. doi:10.1038/nature13241. PMID 24828044. S2CID 4462512.
  51. ^ Kris-Etherton PM, Harris WS, Appel LJ (November 2002). "Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease". Circulation. 106 (21): 2747–57. CiteSeerX 10.1.1.336.457. doi:10.1161/01.CIR.0000038493.65177.94. PMID 12438303.
  52. ^ a b c d e f g h i j k l m "Omega−3 Centre". Omega−3 sources. Omega−3 Centre. Archived from the original on 2008-07-18. Retrieved 2008-07-27.
  53. ^ a b Food and Nutrition Board (2005). Dietary Reference Intakes For Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: Institute of Medicine of the National Academies. pp. 423, 770. ISBN 978-0-309-08537-3. Retrieved 2012-03-06.
  54. ^ Berthold Koletzko; Irene Cetin; J. Thomas Brenna (Nov 2007). "Dietary fat intakes for pregnant and lactating women". British Journal of Nutrition. 98 (5): 873–7. doi:10.1017/S0007114507764747. hdl:11380/610028. PMID 17688705. S2CID 3516064.
  55. ^ Lofstedt A, de Roos B, Fernandes PG (December 2021). "Less than half of the European dietary recommendations for fish consumption are satisfied by national seafood supplies". European Journal of Nutrition. 60 (8): 4219–4228. doi:10.1007/s00394-021-02580-6. PMC 8572203. PMID 33999272.
  56. ^ European Food Safety Authority (EFSA) (2017). "Dietary Reference Values for nutrients Summary report". EFSA Supporting Publications. 14 (12): 23. doi:10.2903/sp.efsa.2017.e15121.
  57. ^ Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, et al. (April 2017). "Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association". Circulation. 135 (15): e867–e884. doi:10.1161/CIR.0000000000000482. PMC 6903779. PMID 28289069.
  58. ^ A 2005 corporate test by Consumer Labs of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.
  59. ^ "Product Review: Omega−3 Fatty Acids (EPA and DHA) from Fish/Marine Oils". ConsumerLab.com. 2005-03-15. Archived from the original on 2018-12-31. Retrieved 2007-08-14.
  60. ^ 2005 study by the Food Safety Authority of Ireland: https://www.fsai.ie/uploadedFiles/Dioxins_milk_survey_2005.pdf Archived 2020-03-22 at the Wayback Machine
  61. ^ "IFOS Home – The International Fish Oil Standards Program". Archived from the original on 2011-08-21. Retrieved 2011-08-21.
  62. ^ Shahidi F, Wanasundara UN (1998-06-01). "Omega−3 fatty acid concentrates: nutritional aspects and production technologies". Trends in Food Science & Technology. 9 (6): 230–40. doi:10.1016/S0924-2244(98)00044-2.
  63. ^ "Revealed: many common omega−3 fish oil supplements are 'rancid'". The Guardian. 2022-01-17. Archived from the original on 2022-01-17. Retrieved 2022-01-17.
  64. ^ "Top 10 Fish Oil Supplements". labdoor. Archived from the original on 2022-01-17. Retrieved 2022-01-17.
  65. ^ Mozaffarian, Rimm EB (2006). "Fish intake, contaminants, and human health: evaluating the risks and the benefits". Journal of the American Medical Association. 15 (1): 1885–1899. doi:10.1001/jama.296.15.1885. ISSN 0098-7484. PMID 17047219.
  66. ^ Falk-Petersen A, Sargent JR, Henderson J, Hegseth EN, Hop H, Okolodkov YB (1998). "Lipids and fatty acids in ice algae and phytoplankton from the Marginal Ice Zone in the Barents Sea". Polar Biology. 20 (1): 41–47. Bibcode:1998PoBio..20...41F. doi:10.1007/s003000050274. ISSN 0722-4060. S2CID 11027523. INIST 2356641.
  67. ^ "Nofima has found new sources of omega-3 for fish feed". The Fish Site. 31 October 2019.
  68. ^ a b Innis SM, Rioux FM, Auestad N, Ackman RG (September 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. doi:10.1093/jn/125.9.2286. PMID 7666244.
  69. ^ Lawson LD, Hughes BG (October 1988). "Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal". Biochemical and Biophysical Research Communications. 156 (2): 960–3. doi:10.1016/S0006-291X(88)80937-9. PMID 2847723.
  70. ^ Beckermann B, Beneke M, Seitz I (June 1990). "[Comparative bioavailability of eicosapentaenoic acid and docosahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers]". Arzneimittel-Forschung (in German). 40 (6): 700–4. PMID 2144420.
  71. ^ Tur JA, Bibiloni MM, Sureda A, Pons A (June 2012). "Dietary sources of omega 3 fatty acids: public health risks and benefits". The British Journal of Nutrition. 107 (Suppl 2): S23-52. doi:10.1017/S0007114512001456. PMID 22591897.
  72. ^ Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, et al. (January 2011). "Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers". Lipids. 46 (1): 37–46. doi:10.1007/s11745-010-3490-4. PMC 3024511. PMID 21042875.
  73. ^ Atkinson A, Siegel V, Pakhomov E, Rothery P (November 2004). "Long-term decline in krill stock and increase in salps within the Southern Ocean". Nature. 432 (7013): 100–3. Bibcode:2004Natur.432..100A. doi:10.1038/nature02996. PMID 15525989. S2CID 4397262.
  74. ^ Orr A (2014). "Malnutrition behind whale strandings". Stuff, Fairfax New Zealand Limited. Archived from the original on 5 April 2019. Retrieved 8 August 2015.
  75. ^ "Krill fisheries and sustainability". Commission for the Conservation of Antarctic Marine Living Resources, Tasmania, Australia. 2015. Archived from the original on 14 April 2019. Retrieved 8 August 2015.
  76. ^ Köhler A, Sarkkinen E, Tapola N, Niskanen T, Bruheim I (March 2015). "Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects--a randomized, single-dose, cross-over trial". Lipids in Health and Disease. 14: 19. doi:10.1186/s12944-015-0015-4. PMC 4374210. PMID 25884846.
  77. ^ Saw CL, Yang AY, Guo Y, Kong AN (December 2013). "Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway". Food and Chemical Toxicology. 62: 869–875. doi:10.1016/j.fct.2013.10.023. PMID 24157545.
  78. ^ Barros MP, Poppe SC, Bondan EF (March 2014). "Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in krill oil". Nutrients. 6 (3): 1293–1317. doi:10.3390/nu6031293. PMC 3967194. PMID 24667135.
  79. ^ Zimmer C (September 17, 2015). "Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story". The New York Times. Archived from the original on January 9, 2019. Retrieved October 11, 2015.
  80. ^ O'Connor A (March 30, 2015). "Fish Oil Claims Not Supported by Research". The New York Times. Archived from the original on May 28, 2018. Retrieved October 11, 2015.
  81. ^ "Seed Oil Fatty Acids – SOFA Database Retrieval". Archived from the original on 2018-12-31. Retrieved 2012-07-21. In German. Google translation Archived 2021-04-29 at the Wayback Machine
  82. ^ "WWW.osel.co.nz - 1st Domains" (PDF). Archived from the original (PDF) on 2012-01-31. Retrieved 2012-07-21.
  83. ^ "WWW.osel.co.nz - 1st Domains" (PDF). Archived from the original (PDF) on 2013-02-05. Retrieved 2012-07-21.
  84. ^ Soltana, Hala; Tekaya, Meriem; Amri, Zahra; El-Gharbi, Sinda; Nakbi, Amel; Harzallah, Arij; Mechri, Beligh; Hammami, Mohamed (April 2016). "Characterization of fig achenes' oil of Ficus carica grown in Tunisia". Food Chemistry. 196: 1125–1130. doi:10.1016/j.foodchem.2015.10.053. PMID 26593597.
  85. ^ Wilkinson J. "Nut Grower's Guide: The Complete Handbook for Producers and Hobbyists" (PDF). Archived (PDF) from the original on 27 September 2007. Retrieved 21 October 2007.
  86. ^ Bartram T (September 2002). Bartram's Encyclopedia of Herbal Medicine: The Definitive Guide to the Herbal Treatments of Diseases. Da Capo Press. p. 271. ISBN 978-1-56924-550-7.
  87. ^ Decsi T, Kennedy K (December 2011). "Sex-specific differences in essential fatty acid metabolism". The American Journal of Clinical Nutrition. 94 (6 Suppl): 1914S–1919S. doi:10.3945/ajcn.110.000893. PMID 22089435.
  88. ^ a b Ganesan B, Brothersen C, McMahon DJ (2014). "Fortification of foods with omega-3 polyunsaturated fatty acids". Critical Reviews in Food Science and Nutrition. 54 (1): 98–114. doi:10.1080/10408398.2011.578221. PMID 24188235. S2CID 44629122.
  89. ^ van Ginneken VJ, Helsper JP, de Visser W, van Keulen H, Brandenburg WA (June 2011). "Polyunsaturated fatty acids in various macroalgal species from North Atlantic and tropical seas". Lipids in Health and Disease. 10 (104): 104. doi:10.1186/1476-511X-10-104. PMC 3131239. PMID 21696609.
  90. ^ Collins ML, Lynch B, Barfield W, Bull A, Ryan AS, Astwood JD (October 2014). "Genetic and acute toxicological evaluation of an algal oil containing eicosapentaenoic acid (EPA) and palmitoleic acid". Food and Chemical Toxicology. 72: 162–8. doi:10.1016/j.fct.2014.07.021. PMID 25057807.
  91. ^ a b West, AL; Miles, EA; Lillycrop, KA; Napier, JA; Calder, PC; Burdge, GC (March 2021). "Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project". Nutrition Bulletin. 46 (1): 60–68. doi:10.1111/nbu.12478. PMC 7986926. PMID 33776584.
  92. ^ Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O (January 2014). "Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop". The Plant Journal. 77 (2): 198–208. doi:10.1111/tpj.12378. PMC 4253037. PMID 24308505.
  93. ^ Coghlan, Andy (31 December 2013). "Designer plants have vital fish oils in their seeds". New Scientist.
  94. ^ "Omega-3 canola". www.csiro.au.
  95. ^ Nutritional, Nuseed. "FDA Acknowledges Nutriterra® Total Omega-3 Canola Oil is a Safe New Dietary Ingredient". www.prnewswire.com (Press release).
  96. ^ "How Omega-6s Usurped Omega-3s In US Diet". Medical News Today. Archived from the original on July 28, 2020. Retrieved Apr 28, 2020.
  97. ^ Trebunová A, Vasko L, Svedová M, Kastel' R, Tucková M, Mach P (July 2007). "The influence of omega-3 polyunsaturated fatty acids feeding on the composition of fatty acids in fatty tissues and eggs of laying hens". DTW. Deutsche Tierarztliche Wochenschrift. 114 (7): 275–279. PMID 17724936.
  98. ^ Cherian G, Sim JS (April 1991). "Effect of feeding full fat flax and canola seeds to laying hens on the fatty acid composition of eggs, embryos, and newly hatched chicks". Poultry Science. 70 (4): 917–22. doi:10.3382/ps.0700917.
  99. ^ Vlaicu PA, Panaite TD, Turcu RP (October 2021). "Enriching laying hens eggs by feeding diets with different fatty acid composition and antioxidants". Scientific Reports. 11 (1): 20707. Bibcode:2021NatSR..1120707V. doi:10.1038/s41598-021-00343-1. PMC 8526598. PMID 34667227.
  100. ^ Colin S (2010-06-03). "Washington Post's Egg Taste Test Says Homegrown And Factory Eggs Taste The Same [UPDATED, POLL]". Huffingtonpost.com. Archived from the original on 2010-06-10. Retrieved 2011-01-03.
  101. ^ Garton GA (August 1960). "Fatty acid composition of the lipids of pasture grasses". Nature. 187 (4736): 511–2. Bibcode:1960Natur.187..511G. doi:10.1038/187511b0. PMID 13826699. S2CID 4296061.
  102. ^ Duckett SK, Wagner DG, Yates LD, Dolezal HG, May SG (August 1993). "Effects of time on feed on beef nutrient composition". Journal of Animal Science. 71 (8): 2079–88. doi:10.2527/1993.7182079x. PMID 8376232.
  103. ^ a b Duckett SK, Neel JP, Fontenot JP, Clapham WM (September 2009). "Effects of winter stocker growth rate and finishing system on: III. Tissue proximate, fatty acid, vitamin, and cholesterol content". Journal of Animal Science. 87 (9): 2961–70. doi:10.2527/jas.2009-1850. PMID 19502506.
  104. ^ Azcona JO, Schang MJ, Garcia PT, Gallinger C, Ayerza Jr R, Coates W (2008). "Omega−3 enriched broiler meat: The influence of dietary alpha-linolenic omega−3 fatty acid sources on growth, performance and meat fatty acid composition". Canadian Journal of Animal Science. 88 (2): 257–69. doi:10.4141/CJAS07081.
  105. ^ "Gourmet Game – Amazing Nutrition Facts". 2019-05-31. Archived from the original on 2009-03-01.
  106. ^ "Natural Health Product Monograph – Seal Oil". Health Canada. June 22, 2009. Archived from the original on 2012-03-19. Retrieved June 20, 2012.
  107. ^ European Parliament (9 November 2009). "MEPs adopt strict conditions for the placing on the market of seal products in the European Union". Hearings. European Parliament. Archived from the original on 14 October 2012. Retrieved 12 March 2010.
  108. ^ Whittle P (2023-06-06). "Canadian company pleads guilty to shipping banned seal oil to US". Associated Press. Archived from the original on 2023-06-08. Retrieved 2023-06-08.
  109. ^ Beck L (9 May 2018). "Omega-3 eggs: healthier choice or marketing gimmick?". The Toronto Globe and Mail. Archived from the original on 10 August 2020. Retrieved 7 March 2019.
  110. ^ Rizos EC, Elisaf MS (June 2017). "Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?". Current Cardiology Reports. 19 (6): 47. doi:10.1007/s11886-017-0856-8. PMID 28432658. S2CID 23585060.
  111. ^ MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, et al. (January 2006). "Effects of omega-3 fatty acids on cancer risk: a systematic review". JAMA. 295 (4): 403–415. doi:10.1001/jama.295.4.403. hdl:10919/79706. PMID 16434631.
  112. ^ Lam, Chung Nga; Watt, Amanda E.; Isenring, Elizabeth A.; de van der Schueren, Marian A.E.; van der Meij, Barbara S. (June 2021). "The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis" (PDF). Clinical Nutrition. 40 (6): 3815–3826. doi:10.1016/j.clnu.2021.04.031. PMID 34130028.
  113. ^ a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.
  114. ^ Bernasconi AA, Wiest MM, Lavie CJ, Milani RV, Laukkanen JA (February 2021). "Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials". Mayo Clinic Proceedings. 96 (2): 304–313. doi:10.1016/j.mayocp.2020.08.034. PMID 32951855.
  115. ^ Kotwal S, Jun M, Sullivan D, Perkovic V, Neal B (November 2012). "Omega 3 Fatty acids and cardiovascular outcomes: systematic review and meta-analysis". Circulation: Cardiovascular Quality and Outcomes. 5 (6): 808–18. doi:10.1161/CIRCOUTCOMES.112.966168. PMID 23110790.
  116. ^ "Omega-3 acid ethyl esters - containing medicinal products for oral in use in secondary prevention after myocardial infarction". European Medicines Agency. 6 June 2019. Archived from the original on 13 April 2019. Retrieved 4 October 2019.
  117. ^ Miller PE, Van Elswyk M, Alexander DD (July 2014). "Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials". American Journal of Hypertension. 27 (7): 885–96. doi:10.1093/ajh/hpu024. PMC 4054797. PMID 24610882.
  118. ^ Morris MC, Sacks F, Rosner B (August 1993). "Does fish oil lower blood pressure? A meta-analysis of controlled trials". Circulation. 88 (2): 523–33. doi:10.1161/01.CIR.88.2.523. PMID 8339414.
  119. ^ Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ (August 1999). "Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans". Hypertension. 34 (2): 253–60. doi:10.1161/01.HYP.34.2.253. PMID 10454450.
  120. ^ Weintraub HS (November 2014). "Overview of prescription omega-3 fatty acid products for hypertriglyceridemia". Postgraduate Medicine. 126 (7): 7–18. doi:10.3810/pgm.2014.11.2828. PMID 25387209. S2CID 12524547.
  121. ^ Wu L, Parhofer KG (December 2014). "Diabetic dyslipidemia". Metabolism. 63 (12): 1469–79. doi:10.1016/j.metabol.2014.08.010. PMID 25242435.
  122. ^ Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. (May 2011). "Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association". Circulation. 123 (20): 2292–333. doi:10.1161/CIR.0b013e3182160726. PMID 21502576.
  123. ^ Skulas-Ray AC, Wilson PW, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, et al. (September 2019). "Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association". Circulation. 140 (12): e673–e691. doi:10.1161/CIR.0000000000000709. PMID 31422671.
  124. ^ Popoff F, Balaciano G, Bardach A, Comandé D, Irazola V, Catalano HN, Izcovich A (June 2019). "Omega 3 fatty acid supplementation after myocardial infarction: a systematic review and meta-analysis". BMC Cardiovascular Disorders. 19 (1): 136. doi:10.1186/s12872-019-1086-3. PMC 6549284. PMID 31164089.
  125. ^ Lombardi M, Carbone S, Del Buono MG, et al. (July 2021). "Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials". European Heart Journal - Cardiovascular Pharmacotherapy. 7 (4): e69–e70. doi:10.1093/ehjcvp/pvab008. PMC 8302253. PMID 33910233.
  126. ^ Gencer B, Djousse L, Al-Ramady OT, et al. (December 2021). "Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis". Circulation. 144 (25): 1981–1990. doi:10.1161/CIRCULATIONAHA.121.055654. PMC 9109217. PMID 34612056.
  127. ^ a b Tam KW, Wu MY, Siddiqui FJ, Chan ES, Zhu Y, Jafar TH, et al. (Cochrane Kidney and Transplant Group) (November 2018). "Omega-3 fatty acids for dialysis vascular access outcomes in patients with chronic kidney disease". The Cochrane Database of Systematic Reviews. 2018 (11): CD011353. doi:10.1002/14651858.CD011353.pub2. PMC 6517057. PMID 30480758.
  128. ^ Robinson LE, Mazurak VC (April 2013). "N-3 polyunsaturated fatty acids: relationship to inflammation in healthy adults and adults exhibiting features of metabolic syndrome". Lipids. 48 (4): 319–332. doi:10.1007/s11745-013-3774-6. PMID 23456976. S2CID 4005634.
  129. ^ Li K, Huang T, Zheng J, Wu K, Li D (February 2014). "Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: a meta-analysis". PLOS ONE. 9 (2): e88103. Bibcode:2014PLoSO...988103L. doi:10.1371/journal.pone.0088103. PMC 3914936. PMID 24505395.
  130. ^ Artiach G, Sarajlic P, Bäck M (February 2020). "Inflammation and its resolution in coronary artery disease: a tightrope walk between omega-6 and omega-3 polyunsaturated fatty acids". Kardiologia Polska. 78 (2): 93–95. doi:10.33963/KP.15202. PMID 32108752.
  131. ^ Kavyani Z, Musazadeh V, Fathi S, Hossein Faghfouri A, Dehghan P, Sarmadi B (October 2022). "Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis". International Immunopharmacology. 111: 109104. doi:10.1016/j.intimp.2022.109104. PMID 35914448. S2CID 251209023.
  132. ^ Miles EA, Calder PC (June 2012). "Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis". The British Journal of Nutrition. 107 (Suppl 2): S171-84. doi:10.1017/S0007114512001560. PMID 22591891.
  133. ^ "Herbal Remedies, Supplements & Acupuncture for Arthritis - Supplements for arthritis". American College of Rheumatology. June 2018. Archived from the original on 20 March 2022. Retrieved 6 April 2019.
  134. ^ "Rheumatoid Arthritis: In-Depth". National Center for Complementary and Alternative Medicine. January 2019. Archived from the original on 28 July 2020. Retrieved 6 April 2019.
  135. ^ Bloch MH, Qawasmi A (October 2011). "Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis". Journal of the American Academy of Child and Adolescent Psychiatry. 50 (10): 991–1000. doi:10.1016/j.jaac.2011.06.008. PMC 3625948. PMID 21961774.
  136. ^ Gillies D, Leach MJ, Perez Algorta G (April 2023). "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents". The Cochrane Database of Systematic Reviews. 2023 (4): CD007986. doi:10.1002/14651858.CD007986.pub3. PMC 10103546. PMID 37058600.
  137. ^ Tan ML, Ho JJ, Teh KH (December 2012). Tan ML (ed.). "Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders". The Cochrane Database of Systematic Reviews. 12: CD009398. doi:10.1002/14651858.CD009398.pub2. PMID 23235675.
  138. ^ Ortega RM, Rodríguez-Rodríguez E, López-Sobaler AM (June 2012). "Effects of omega 3 fatty acids supplementation in behavior and non-neurodegenerative neuropsychiatric disorders". The British Journal of Nutrition. 107 (Suppl 2): S261–S270. doi:10.1017/S000711451200164X. PMID 22591900.
  139. ^ "Omega−3 long chain polyunsaturated fatty acids to prevent preterm birth: a meta-analysis of randomized controlled trials". www.crd.york.ac.uk. Archived from the original on 2018-07-18. Retrieved 2016-03-01.
  140. ^ Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M (November 2018). "Omega-3 fatty acid addition during pregnancy". The Cochrane Database of Systematic Reviews. 2018 (11): CD003402. doi:10.1002/14651858.cd003402.pub3. PMC 6516961. PMID 30480773.
  141. ^ a b Firouzabadi FD, Shab-Bidar S, Jayedi A (March 2022). "The effects of omega-3 polyunsaturated fatty acids supplementation in pregnancy, lactation, and infancy: An umbrella review of meta-analyses of randomized trials". Pharmacological Research. 177: 106100. doi:10.1016/j.phrs.2022.106100. PMID 35104631. S2CID 246419684.
  142. ^ Deane, Katherine H. O.; Jimoh, Oluseyi F.; Biswas, Priti; O'Brien, Alex; Hanson, Sarah; Abdelhamid, Asmaa S.; Fox, Chris; Hooper, Lee (March 2021). "Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials" (PDF). The British Journal of Psychiatry. 218 (3): 135–142. doi:10.1192/bjp.2019.234. PMID 31647041.
  143. ^ Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, et al. (October 2019). "The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials". World Psychiatry. 18 (3): 308–324. doi:10.1002/wps.20672. PMC 6732706. PMID 31496103.
  144. ^ Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R (November 2021). "Omega-3 fatty acids for depression in adults". The Cochrane Database of Systematic Reviews. 2021 (11): CD004692. doi:10.1002/14651858.CD004692.pub5. PMC 8612309. PMID 34817851.
  145. ^ Montgomery P, Richardson AJ (April 2008). "Omega-3 fatty acids for bipolar disorder". The Cochrane Database of Systematic Reviews (2): CD005169. doi:10.1002/14651858.CD005169.pub2. PMID 18425912.
  146. ^ Zhang MM, Zou Y, Li SM, Wang L, Sun YH, Shi L, et al. (June 2020). "The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials". Translational Psychiatry. 10 (1): 193. doi:10.1038/s41398-020-00886-3. PMC 7299975. PMID 32555188.
  147. ^ Wani, Ab Latif; Bhat, Sajad Ahmad; Ara, Anjum (September 2015). "Omega-3 fatty acids and the treatment of depression: a review of scientific evidence". Integrative Medicine Research. 4 (3): 132–141. doi:10.1016/j.imr.2015.07.003. PMC 5481805. PMID 28664119.
  148. ^ Richard P. Bazinet (2020). "Brain eicosapentaenoic acid metabolism as a lead for novel therapeutics in major depression". Science Direct.
  149. ^ David Mischoulon (27 October 2020). "Omega-3 fatty acids for mood disorders". Harvard Health Publishing.
  150. ^ Sanhueza C, Ryan L, Foxcroft DR (February 2013). "Diet and the risk of unipolar depression in adults: systematic review of cohort studies". Journal of Human Nutrition and Dietetics. 26 (1): 56–70. doi:10.1111/j.1365-277X.2012.01283.x. PMID 23078460.
  151. ^ Appleton KM, Rogers PJ, Ness AR (March 2010). "Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood". The American Journal of Clinical Nutrition. 91 (3): 757–70. doi:10.3945/ajcn.2009.28313. PMID 20130098.
  152. ^ a b Bloch MH, Hannestad J (December 2012). "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.
  153. ^ Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A (April 2016). "Omega-3 fatty acids for the treatment of dementia". The Cochrane Database of Systematic Reviews. 2016 (4): CD009002. doi:10.1002/14651858.CD009002.pub3. PMC 7117565. PMID 27063583.
  154. ^ Mazereeuw G, Lanctôt KL, Chau SA, Swardfager W, Herrmann N (July 2012). "Effects of ω-3 fatty acids on cognitive performance: a meta-analysis". Neurobiology of Aging. 33 (7): 1482.e17–1482.e29. doi:10.1016/j.neurobiolaging.2011.12.014. PMID 22305186. S2CID 2603173.
  155. ^ Forbes SC, Holroyd-Leduc JM, Poulin MJ, Hogan DB (December 2015). "Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials". Canadian Geriatrics Journal. 18 (4): 231–245. doi:10.5770/cgj.18.189. PMC 4696451. PMID 26740832.
  156. ^ Alex A, Abbott KA, McEvoy M, Schofield PW, Garg ML (July 2020). "Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis". Nutrition Reviews. 78 (7): 563–578. doi:10.1093/nutrit/nuz073. PMID 31841161.
  157. ^ Wood AH, Chappell HF, Zulyniak MA (March 2022). "Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer's disease". European Journal of Nutrition. 61 (2): 589–604. doi:10.1007/s00394-021-02655-4. PMC 8854294. PMID 34392394.
  158. ^ Brainard JS, Jimoh OF, Deane KH, Biswas P, Donaldson D, Maas K, Abdelhamid AS, Hooper L (October 2020). "Omega-3, Omega-6, and Polyunsaturated Fat for Cognition: Systematic Review and Meta-analysis of Randomized Trials" (PDF). Journal of the American Medical Directors Association. 21 (10): 1439–1450.e21. doi:10.1016/j.jamda.2020.02.022. PMID 32305302.
  159. ^ Bradbury J (May 2011). "Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain". Nutrients. 3 (5): 529–554. doi:10.3390/nu3050529. PMC 3257695. PMID 22254110.
  160. ^ Harris WS, Baack ML (January 2015). "Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity". Journal of Perinatology. 35 (1): 1–7. doi:10.1038/jp.2014.195. PMC 4281288. PMID 25357095.
  161. ^ Hüppi PS (March 2008). "Nutrition for the brain: commentary on the article by Isaacs et al. on page 308". Pediatric Research. 63 (3): 229–231. doi:10.1203/pdr.0b013e318168c6d1. PMID 18287959. S2CID 6564743.
  162. ^ Horrocks LA, Yeo YK (September 1999). "Health benefits of docosahexaenoic acid (DHA)". Pharmacological Research. 40 (3): 211–225. doi:10.1006/phrs.1999.0495. PMID 10479465.
  163. ^ Lawrenson JG, Evans JR (April 2015). "Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration". The Cochrane Database of Systematic Reviews. 2015 (4): CD010015. doi:10.1002/14651858.CD010015.pub3. PMC 7087473. PMID 25856365.
  164. ^ Lohner S, Decsi T. Role of Long-Chain Polyunsaturated Fatty Acids in the Prevention and Treatment of Atopic Diseases. In: Polyunsaturated Fatty Acids: Sources, Antioxidant Properties, and Health Benefits (edited by: Angel Catalá). NOVA Publishers. 2013. Chapter 11, pp. 1–24. (ISBN 978-1-62948-151-7)
  165. ^ Lohner S, Fekete K, Decsi T (July 2013). "Lower n-3 long-chain polyunsaturated fatty acid values in patients with phenylketonuria: a systematic review and meta-analysis". Nutrition Research. 33 (7): 513–20. doi:10.1016/j.nutres.2013.05.003. PMID 23827125.
  166. ^ Muley P, Shah M, Muley A (2015). "Omega-3 Fatty Acids Supplementation in Children to Prevent Asthma: Is It Worthy?-A Systematic Review and Meta-Analysis". Journal of Allergy. 2015: 312052. doi:10.1155/2015/312052. PMC 4556859. PMID 26357518.
  167. ^ Brown, Tracey J; Brainard, Julii; Song, Fujian; Wang, Xia; Abdelhamid, Asmaa; Hooper, Lee; PUFAH, Group (21 August 2019). "Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials". BMJ. 366: l4697. doi:10.1136/bmj.l4697. PMC 6699594. PMID 31434641.
  168. ^ Boosting omega-3 fatty acid intake is unlikely to prevent type 2 diabetes (Preprint). 12 November 2019. doi:10.3310/signal-000833.
  169. ^ Delpino FM, Figueiredo LM, da Silva BG, et al. (2022). "Omega-3 supplementation and diabetes: A systematic review and meta-analysis". Critical Reviews in Food Science and Nutrition. 62 (16): 4435–4448. doi:10.1080/10408398.2021.1875977. PMID 33480268. S2CID 231677714.
  170. ^ Adeyemi Fatai Odetayo, Luqman Aribidesi Olayaki (23 October 2023). "Omega 3 fatty acid improves sexual and erectile function in BPF-treated rats by upregulating NO/cGMP signaling and steroidogenic enzymes activities". Nature.com.

Further reading

[edit]
[edit]