Docosahexaenoic acid

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Docosahexaenoic acid
DHA numbers.svg
Docosahexaenoic-acid-3D-balls.png
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Names
Preferred IUPAC name
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosa-4,7,10,13,16,19-hexaenoic acid
Other names
cervonic acid
DHA
doconexent (INN)
Identifiers
3D model (JSmol)
AbbreviationsDHA
1715505
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.118.398 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 612-950-9
KEGG
PubChem CID
UNII
  • InChI=1S/C22H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24/h3-4,6-7,9-10,12-13,15-16,18-19H,2,5,8,11,14,17,20-21H2,1H3,(H,23,24)/b4-3-,7-6-,10-9-,13-12-,16-15-,19-18- Yes check.svgY
    Key: MBMBGCFOFBJSGT-KUBAVDMBSA-N Yes check.svgY
  • InChI=1/C22H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24/h3-4,6-7,9-10,12-13,15-16,18-19H,2,5,8,11,14,17,20-21H2,1H3,(H,23,24)/b4-3-,7-6-,10-9-,13-12-,16-15-,19-18-
    Key: MBMBGCFOFBJSGT-KUBAVDMBBZ
  • O=C(O)CC\C=C/C/C=C\C\C=C/C\C=C/C\C=C/C\C=C/CC
Properties
C22H32O2
Molar mass 328.488 g/mol
Density 0.943 g/cm3
Melting point −44 °C (−47 °F; 229 K)
Boiling point 446.7 °C (836.1 °F; 719.8 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(n-3). [1] It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk (breast milk), fatty fish, fish oil, or algae oil. [1] [2] The consumption of DHA (e.g., from fatty fish such as salmon, herring, mackerel and sardines) contributes to numerous physiological benefits, including cognition. [3] [4] As a component of neuronal membranes, the function of DHA is to support neuronal conduction and to allow the optimal functioning of neuronal membrane proteins (such as receptors and enzymes). [5]

Contents

Structurally, DHA is a carboxylic acid (-oic acid) with a 22-carbon chain (docosa- derives from the Ancient Greek for 22) and six (hexa-) cis double bonds (-en-); [6] with the first double bond located at the third carbon from the omega end. [7] Its trivial name is cervonic acid (from the Latin word cerebrum for "brain"), its systematic name is all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid.

In organisms that do not eat algae containing DHA nor animal products containing DHA, DHA is instead produced internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants). [8] Limited amounts of eicosapentaenoic and docosapentaenoic acids are possible products of α-linolenic acid metabolism in young women [9] and men. [8] DHA in breast milk is important for the developing infant. [10] Rates of DHA production in women are 15% higher than in men. [11]

DHA is a major fatty acid in brain phospholipids and the retina. Preliminary research has investigated its potential benefit in Alzheimer's disease, [1] [12] and cardiovascular disease, [13] and other disorders. [1]

Central nervous system constituent

DHA is the most abundant omega-3 fatty acid in the brain and retina. [14] DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of a neuronal plasma membrane is composed of DHA. [15] DHA modulates the carrier-mediated transport of choline, glycine, and taurine, the function of delayed rectifier potassium channels, and the response of rhodopsin contained in the synaptic vesicles. [16] [17]

Phosphatidylserine (PS) – which contains high DHA content – has roles in neuronal signaling and neurotransmitter synthesis, [14] and DHA deficiency is associated with cognitive decline. [14] [18] DHA levels are reduced in the brain tissue of severely depressed people. [19] [20]

Biosynthesis

Aerobic eukaryote pathway

Aerobic eukaryotes, specifically microalgae, mosses, fungi, and some animals, perform biosynthesis of DHA as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase enzymes. This pathway, originally identified in Thraustochytrium, applies to these groups: [21]

  1. a desaturation at the sixth carbon of alpha-linolenic acid by a delta 6 desaturase to produce stearidonic acid (SDA, 18:4 ω-3),
  2. elongation of the stearidonic acid by a delta 6 elongase to produce eicosatetraenoic acid (ETA, 20:4 ω-3),
  3. desaturation at the fifth carbon of eicosatetraenoic acid by a delta 5 desaturase to produce eicosapentaenoic acid (EPA, 20:5 ω-3),
  4. elongation of eicosapentaenoic acid by a delta 5 elongase to produce docosapentaenoic acid (DPA, 22:5 ω-3), and
  5. desaturation at the fourth carbon of docosapentaenoic acid by a delta 4 desaturase to produce DHA.

Mammals

In humans, DHA is either obtained from the diet or may be converted in small amounts from eicosapentaenoic acid (EPA, 20:5, ω-3). With the identification of FADS2 as a human Δ4-desaturase in 2015, it is now known that humans also follow the whole "aerobic eukaryote" pathway, involving Δ5-elongation to DPA and Δ4-desaturation to DHA. [22]

A "Sprecher's shunt" hypothesis, proposed in 1991, postulates that EPA is twice elongated to 24:5 ω-3, then desaturated to 24:6 ω-3 (via delta 6 desaturase) in the mitochondria, then shortened to DHA (22:6 ω-3) via beta oxidation in the peroxisome. The hypothesis became accepted for a while because scientists have (until 2015) long tried and failed to find a Δ4-desaturase in mammals. [23] [24] However, the shunt model does not match clinical data, specifically as patients with beta oxidation defects do not display issues in DHA synthesis. With the identification of a Δ4-desaturase, it is considered outdated. [22]

Anaerobic pathway

Marine bacteria and the microalgae Schizochytrium use an anerobic polyketide synthase pathway to synthesize DHA. [21]

Metabolism

DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others. [25]

The enzyme CYP2C9 metabolizes DHA to epoxydocosapentaenoic acids (EDPs; primarily 19,20-epoxy-eicosapentaenoic acid isomers [i.e. 10,11-EDPs]). [26]

Potential health effects

Cardiovascular

Though mixed and plagued by methodological inconsistencies, there is now convincing evidence from ecological, RCTs, meta-analyses and animal trials show a benefit for omega-3 dietary intake for cardiovascular health. [1] [13] Of the n-3 FAs, DHA has been argued to be the most beneficial due to its preferential uptake in the myocardium, its strongly anti-inflammatory activity and its metabolism toward neuroprotectins and resolvins, the latter of which directly contribute to cardiac function. [27]

DHA is associated with its role in cardiovascular protection and lowering the risk of coronary artery disease. DHA supplementation has been shown to improve high-density lipoprotein (‘good cholesterol’), and lower total cholesterol as well as blood pressure levels. [28]

Pregnancy and lactation

Foods high in omega-3 fatty acids may be recommended to women who want to become pregnant or when nursing. [29] A working group from the International Society for the Study of Fatty Acids and Lipids recommended 300 mg/day of DHA for pregnant and lactating women, whereas the average consumption was between 45 mg and 115 mg per day of the women in the study, similar to a Canadian study. [30]

Brain and visual functions

A major structural component of the mammalian central nervous system, DHA is the most abundant omega−3 fatty acid in the brain and retina. [31] Brain and retinal function rely on dietary intake of DHA to support a broad range of cell membrane and cell signaling properties, particularly in grey matter and retinal photoreceptor cell outer segments, which are rich in membranes. [32] [33]

A systematic review found that DHA had no significant benefits in improving visual field in individuals with retinitis pigmentosa. [34] Animal research shows effect of oral intake of deuterium-reinforced DHA (D-DHA) for prevention of macular degeneration. [35]

Asthma

Omega-3 PUFAs such as DHA and eicosapentaenoic acid (EPA) are effective in the prevention and treatment of asthma and allergic diseases. [36]

Nutrition

Algae-based DHA supplements DHA pills.jpg
Algae-based DHA supplements

Ordinary types of cooked salmon contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams. [37] Additional rich seafood sources of DHA include caviar (3400 mg per 100 grams), anchovies (1292 mg per 100 grams), mackerel (1195 mg per 100 grams), and cooked herring (1105 mg per 100 grams). [37]

Brains from mammals taken as food are also a good direct source. Beef brain, for example, contains approximately 855 mg of DHA per 100 grams in a serving. [38] While DHA may be the primary fatty acid found in certain specialized tissues, these tissues, aside from the brain, are typically small in size, such as the seminiferous tubules and the retina. As a result, animal-based foods, excluding the brain, generally offer minimal amounts of preformed DHA. [39]

Discovery of algae-based DHA

In the early 1980s, NASA sponsored scientific research on a plant-based food source that could generate oxygen and nutrition on long-duration space flights. Certain species of marine algae produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA and arachidonic acid. [40]

Use as a food additive

DHA is widely used as a food supplement. It was first used primarily in infant formulas. [41] In 2019, the US Food and Drug Administration published qualified health claims for DHA. [42]

Some manufactured DHA is a vegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3s such as EPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive. [43]

Studies of vegetarians and vegans

Vegetarian diets typically contain limited amounts of DHA, and vegan diets typically contain no DHA. [44] In preliminary research, algae-based supplements increased DHA levels. [45] While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans, breast milk levels remain a concern for supplying adequate DHA to the infant. [44]

DHA and EPA in fish oils

Fish oil is widely sold in capsules containing a mixture of omega-3 fatty acids, including EPA and DHA. Oxidized fish oil in supplement capsules may contain lower levels of EPA and DHA. [46] [47] Light, oxygen exposure, and heat can all contribute to oxidation of fish oil supplements. [46] [47] Buying a quality product that is kept cold in storage and then keeping it in a refrigerator can help minimize oxidation. [48]

As optimal DHA level is important for brain development and maturation, there are established daily recommendations for DHA intake in children. [1] [ medical citation needed ]

The table below shows the daily DHA / DHA + EPA intake recommended for children of different ages:

PUFAsAge (years)Recommended daily intake
DHA1 - 210 – 12 mg/kg/day
DHA + EPA2 - 4100 – 150 mg/day
4 - 6150 – 200 mg/day
6 - 10200 – 250 mg/day

Experts recommend DHA intake of 10–12 mg/day for children 12–24 months, 100–150 mg/day of DHA+EPA for children 2–4 years old and 150–200 mg/day of DHA+EPA for children 4–6 years old. [1] [ medical citation needed ]

See also

Related Research Articles

Omega−3 fatty acids, also called Omega−3 oils, ω−3 fatty acids, Ω-3 Fatty acids or n−3 fatty acids, 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. 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. 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. DHA and EPA accumulate in fish that eat these algae. 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, and algae oil.

Essential fatty acids, or EFAs, are fatty acids that are required by humans and other animals for normal physiological function that cannot be synthesized in the body⁠–either at all or in sufficient quantities – and thus must be obtained from a dietary source. Essential nutrients are indispensable for various cellular metabolic processes and for the maintenance and function of tissues and organs.

α-Linolenic acid Chemical compound

α-Linolenic acid, also known as alpha-linolenic acid (ALA), is an n−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, walnuts, chia, hemp, and many common vegetable oils.

<span class="mw-page-title-main">Krill oil</span> Commercial oil product from krill

Krill oil is an extract prepared from a species of Antarctic krill, Euphausia superba. Processed krill oil is commonly sold as a dietary supplement. Two components of krill oil are omega-3 fatty acids similar to those in fish oil, and phospholipid-derived fatty acids (PLFA), mainly phosphatidylcholine. Fishing for krill where previously the focus was on marine life of higher trophic level is an example of fishing down the food web.

Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body and improve hypertriglyceridemia. There has been a great deal of controversy in the 21st century about the role of fish oil in cardiovascular disease, with recent meta-analyses reaching different conclusions about its potential impact.

<span class="mw-page-title-main">Vegetarian nutrition</span> Nutritional and human health aspects of vegetarian diets

Vegetarian nutrition is the set of health-related challenges and advantages of vegetarian diets.

<span class="mw-page-title-main">Eicosapentaenoic acid</span> Chemical compound

Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five cis double bonds; the first double bond is located at the third carbon from the omega end.

Dihomo-γ-linolenic acid (DGLA) is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 (ω−6). DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product of γ-linolenic acid. GLA, in turn, is a desaturation product of linoleic acid. DGLA is made in the body by the elongation of GLA, by an efficient enzyme which does not appear to suffer any form of (dietary) inhibition. DGLA is an extremely uncommon fatty acid, found only in trace amounts in animal products.

Fatty acid desaturases are a family of enzymes that convert saturated fatty acids into unsaturated fatty acids and polyunsaturated fatty acids. For the common fatty acids of the C18 variety, desaturases convert stearic acid into oleic acid. Other desaturases convert oleic acid into linoleic acid, which is the precursor to alpha-linolenic acid, gamma-linolenic acid, and eicosatrienoic acid.

Eicosatetraenoic acid (ETA) designates any straight chain tetra-unsaturated 20-carbon fatty acid. The pure compounds, which are rarely encountered, are colorless oils. Two isomers, both of them essential fatty acids, are of particular interest:

<span class="mw-page-title-main">Essential fatty acid interactions</span>

There is a wide variety of fatty acids found in nature. Two classes of fatty acids are considered essential, the omega-3 and omega-6 fatty acids. Essential fatty acids are necessary for humans but cannot be synthesized by the body and must therefore be obtained from food. Omega-3 and omega-6 are used in some cellular signaling pathways and are involved in mediating inflammation, protein synthesis, and metabolic pathways in the human body.

Docosapentaenoic acid (DPA) designates any straight open chain polyunsaturated fatty acid (PUFA) which contains 22 carbons and 5 double bonds. DPA is primarily used to designate two isomers, all-cis-4,7,10,13,16-docosapentaenoic acid and all-cis-7,10,13,16,19-docosapentaenoic acid. They are also commonly termed n-6 DPA and n-3 DPA, respectively; these designations describe the position of the double bond being 6 or 3 carbons closest to the (omega) carbon at the methyl end of the molecule and is based on the biologically important difference that n-6 and n-3 PUFA are separate PUFA classes, i.e. the omega-6 fatty acids and omega-3 fatty acids, respectively. Mammals, including humans, can not interconvert these two classes and therefore must obtain dietary essential PUFA fatty acids from both classes in order to maintain normal health.

<span class="mw-page-title-main">Linoleoyl-CoA desaturase</span> Class of enzymes

Linoleoyl-CoA desaturase (also Delta 6 desaturase, EC 1.14.19.3) is an enzyme that converts between types of fatty acids, which are essential nutrients in the human body. The enzyme mainly catalyzes the chemical reaction

<span class="mw-page-title-main">CYP4F8</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.

<span class="mw-page-title-main">Omega-3 acid ethyl esters</span> Pharmaceutical product

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. Together with dietary changes, they are used to treat high blood triglycerides which may reduce the risk of pancreatitis. 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. Omega-3-acid ethyl esters are taken by mouth.

Omega-3 carboxylic acids (Epanova) is a formerly marketed yet still not an Food And Drug Administration (FDA) approved prescription medication–since taken off market by the manufacturer–used alongside a low fat and low cholesterol diet that lowers high triglyceride (fat) levels in adults with very high levels. This was the third class of fish oil-based drug, after omega-3 acid ethyl esters and ethyl eicosapentaenoic acid (Vascepa), to be approved for use as a drug. The first approval by US Food and Drug Administration was granted 05 May 2014. These fish oil drugs are similar to fish oil dietary supplements, but the ingredients are better controlled and have been tested in clinical trials. Specifically, Epanova contained at least 850 mg omega-3-acid ethyl esters per 1 g capsule.

<span class="mw-page-title-main">Epoxydocosapentaenoic acid</span> Group of chemical compounds

Epoxide docosapentaenoic acids are metabolites of the 22-carbon straight-chain omega-3 fatty acid, docosahexaenoic acid (DHA). Cell types that express certain cytochrome P450 (CYP) epoxygenases metabolize polyunsaturated fatty acids (PUFAs) by converting one of their double bonds to an epoxide. In the best known of these metabolic pathways, cellular CYP epoxygenases metabolize the 20-carbon straight-chain omega-6 fatty acid, arachidonic acid, to epoxyeicosatrienoic acids (EETs); another CYP epoxygenase pathway metabolizes the 20-carbon omega-3 fatty acid, eicosapentaenoic acid (EPA), to epoxyeicosatetraenoic acids (EEQs). CYP epoxygenases similarly convert various other PUFAs to epoxides. These epoxide metabolites have a variety of activities. However, essentially all of them are rapidly converted to their corresponding, but in general far less active, vicinal dihydroxy fatty acids by ubiquitous cellular soluble epoxide hydrolase. Consequently, these epoxides, including EDPs, operate as short-lived signaling agents that regulate the function of their parent or nearby cells. The particular feature of EDPs distinguishing them from EETs is that they derive from omega-3 fatty acids and are suggested to be responsible for some of the beneficial effects attributed to omega-3 fatty acids and omega-3-rich foods such as fish oil.

<span class="mw-page-title-main">Epoxyeicosatetraenoic acid</span> Chemical compound

Epoxyeicosatetraenoic acids are a set of biologically active epoxides that various cell types make by metabolizing the omega 3 fatty acid, eicosapentaenoic acid (EPA), with certain cytochrome P450 epoxygenases. These epoxygenases can metabolize EPA to as many as 10 epoxides that differ in the site and/or stereoisomer of the epoxide formed; however, the formed EEQs, while differing in potency, often have similar bioactivities and are commonly considered together.

In general, cognitive support diets are formulated to include nutrients that have a known role in brain development, function and/or maintenance, with the goal of improving and preserving mental processes such as attentiveness, short-term and long-term memory, learning, and problem solving. Currently, there is very little conclusive research available regarding cat cognition as standardized tests for evaluating cognitive ability are less established and less reliable than cognitive testing apparatus used in other mammalian species, like dogs. Much of what is known about feline cognition has been inferred from a combination of owner-reported behaviour, brain necropsies, and comparative cognitive neurology of related animal models. Cognition claims appear primarily on kitten diets which include elevated levels of nutrients associated with optimal brain development, although there are now diets available for senior cats that include nutrients to help slow the progression of age-related changes and prevent cognitive decline. Cognition diets for cats contain a greater portion of omega-3 fatty acids, especially docosahexaenoic acid (DHA) as well as eicosapentaenoic acid (EPA), and usually feature a variety of antioxidants and other supporting nutrients thought to have positive effects on cognition.

<span class="mw-page-title-main">Seaweed oil</span>

Seaweed oil, also called algae oil or algal oil, is used for making food, with the purified product almost colorless and odorless. It is also under development as a possible alternative fuel and manufacturing agent.

References

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  2. ↑ Guesnet P, Alessandri JM (2011). "Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations". Biochimie. 93 (1): 7–12. doi:10.1016/j.biochi.2010.05.005. PMID   20478353.
  3. ↑ Calder PC (2016). "Docosahexaenoic acid (Review)". Annals of Nutrition and Metabolism. 69 Suppl 1: 7–21. doi:10.1159/000448262. PMID   27842299.
  4. ↑ Horrocks, L. A.; Yeo, Y. K. (1999). "Health benefits of docosahexaenoic acid (DHA)". Pharmacological Research. 40 (3): 211–225. doi:10.1006/phrs.1999.0495. ISSN   1043-6618. PMID   10479465.
  5. ↑ Sinclair, Andrew James (2019). "Docosahexaenoic acid and the brain- what is its role?" (PDF). Asia Pacific Journal of Clinical Nutrition. 28 (4): 675–688. doi:10.6133/apjcn.201912_28(4).0002. ISSN   1440-6047. PMID   31826363.
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  7. ↑ The omega end is the one furthest from the carboxyl group.
  8. 1 2 Burdge, G. C.; Jones, A. E.; Wootton, S. A. (2002). "Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men". British Journal of Nutrition. 88 (4): 355–363. doi: 10.1079/BJN2002662 . PMID   12323085.
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  15. ↑ Singh, Meharban (March 2005). "Essential fatty acids, DHA and the human brain" (PDF). Indian Journal of Pediatrics. 72 (3): 239–242. doi:10.1007/BF02859265. PMID   15812120. S2CID   5067744. Archived from the original (PDF) on February 27, 2012. Retrieved October 8, 2007.
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  17. ↑ Spector, Arthur A. (1999). "Essentiality of fatty acids". Lipids. 34: S1–S3. doi:10.1007/BF02562220. PMID   10419080. S2CID   4061017.
  18. ↑ Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG (October 2005). "A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease". J Clin Invest. 115 (10): 2774–83. doi:10.1172/JCI25420. PMC   1199531 . PMID   16151530.
  19. ↑ McNamara RK, Hahn CG, Jandacek R, et al. (2007). "Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder". Biol. Psychiatry. 62 (1): 17–24. doi:10.1016/j.biopsych.2006.08.026. PMID   17188654. S2CID   32898004.
  20. ↑ McNamara, R. K.; Jandacek, R; Tso, P; Dwivedi, Y; Ren, X; Pandey, G. N. (2013). "Lower docosahexaenoic acid concentrations in the postmortem prefrontal cortex of adult depressed suicide victims compared with controls without cardiovascular disease". Journal of Psychiatric Research. 47 (9): 1187–91. doi:10.1016/j.jpsychires.2013.05.007. PMC   3710518 . PMID   23759469.
  21. 1 2 Qiu, Xiao (2003-02-01). "Biosynthesis of docosahexaenoic acid (DHA, 22:6-4, 7,10,13,16,19): two distinct pathways". Prostaglandins, Leukotrienes and Essential Fatty Acids. 68 (2): 181–186. doi:10.1016/S0952-3278(02)00268-5. ISSN   0952-3278. PMID   12538082.
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