Docosahexaenoic acid/ja: Difference between revisions

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

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-trans isomerism|cis]]'' [[double bond]]s (''-en-''); 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|α-linolenic acid]], a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants). Limited amounts of [[Eicosapentaenoic acid|eicosapentaenoic]] and [[docosapentaenoic acid]]s are possible products of α-linolenic acid metabolism in young women and men. DHA in [[breast milk]] is important for the developing infant. Rates of DHA production in women are 15% higher than in men.

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

==Central nervous system constituent==

DHA is the most abundant omega-3 fatty acid in the brain and retina. DHA comprises 40% of the [[polyunsaturated fatty acid]]s (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of a [[neuron]]al [[plasma membrane]] is composed of DHA. DHA modulates the carrier-mediated transport of choline, glycine, and taurine, the function of delayed rectifier [[potassium channel]]s, and the response of [[rhodopsin]] contained in the [[synaptic vesicle]]s.

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

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==Biosynthesis==

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=== Aerobic eukaryote pathway ===

Aerobic eukaryotes, specifically microalgae, [[moss]]es, [[Fungus|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 [[enzyme]]s. This pathway, originally identified in ''Thraustochytrium'', applies to these groups:

# a desaturation at the sixth carbon of [[α-Linolenic acid|alpha-linolenic acid]] by a delta 6 desaturase to produce [[stearidonic acid]] (SDA, 18:4 ω-3),

# elongation of the [[stearidonic acid]] by a delta 6 elongase to produce [[eicosatetraenoic acid]] (ETA, 20:4 ω-3),

# desaturation at the fifth carbon of  [[eicosatetraenoic acid]] by a delta 5 desaturase to produce [[eicosapentaenoic acid]] (EPA, 20:5 ω-3),

# elongation of [[eicosapentaenoic acid]] by a delta 5 elongase to produce [[docosapentaenoic acid]] (DPA, 22:5 ω-3), and

# desaturation at the fourth carbon of [[docosapentaenoic acid]] by a delta 4 desaturase to produce DHA.

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=== 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.

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. 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.

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=== Anaerobic pathway ===

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

==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.

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

==Potential health effects==

{{See also|Omega-3 fatty acid#Health effects}}

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===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. 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.

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===Pregnancy and lactation===

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

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===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. 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.

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

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=== Asthma ===

==Nutrition==

[[File:DHA pills.jpg|thumb|Algae-based DHA supplements]]

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

[[Brain as food|Brains from mammals taken as food]] are also a good direct source. Beef brain, for example, contains approximately 855&nbsp;mg of DHA per 100 grams in a serving. 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.

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===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 flight]]s. 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]].

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===Use as a food additive===

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

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 [[Eicosapentaenoic acid|EPA]]. Both fish oil and DHA are odorless and tasteless after processing as a food additive.

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===Studies of vegetarians and vegans===

{{Main|Vegetarian nutrition#Omega-3 fatty acids}}

[[Vegetarian]] diets typically contain limited amounts of DHA, and [[vegan]] diets typically contain no DHA. In preliminary research, algae-based [[dietary supplement|supplements]] increased DHA levels. 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.

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===DHA and EPA in fish oils===

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

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===Recommended daily DHA intake for children===

|Age (years)

|Recommended daily intake

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.

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==See also==

* [[DHA-clozapine]]

* [[List of omega-3 fatty acids]]

* [[Polyunsaturated fatty acid]]s

{{Fatty acids}}

{{Retinoid receptor modulators}}