Docosahexaenoic acid (DHA) is an

omega-3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, 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 chem ...

that is a primary structural component of the human

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consistin ...

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

, and

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from

alpha-linolenic acid ''alpha''-Linolenic acid (ALA), also known as α-Linolenic acid (from Greek ''alpha'' meaning "first" and ''linon'' meaning flax), is an ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, wa ...

or obtained directly from maternal milk (breast milk), fatty fish, fish oil, or algae oil. DHA's structure is a carboxylic acid (-''oic acid'') with a 22-

carbon chain In chemistry, catenation is the bonding of atoms of the same element into a series, called a ''chain''. A chain or a ring shape may be ''open'' if its ends are not bonded to each other (an open-chain compound), or ''closed'' if they are bonde ...

(''docosa-'' derives from the

Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic peri ...

for 22) and six (''hexa-'') ''

cis Cis or cis- may refer to: Places * Cis, Trentino, in Italy * In Poland: ** Cis, Świętokrzyskie Voivodeship, south-central ** Cis, Warmian-Masurian Voivodeship, north Math, science and biology * cis (mathematics) (cis(''θ'')), a trigonome ...

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...

s (''-en-''); with the first double bond located at the third carbon from the omega end. Its

trivial name In chemistry, a trivial name is a non systematic name for a chemical substance. That is, the name is not recognized according to the rules of any formal system of chemical nomenclature such as IUPAC inorganic or IUPAC organic nomenclature. A ...

is cervonic acid (from the

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

word ''cerebrum'' for "brain"), its

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

is ''all-cis''-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n−3) in the nomenclature of fatty acids. Most of the docosahexaenoic acid in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms the further they are up the food chain. DHA is also commercially manufactured from microalgae: '' Crypthecodinium cohnii'' and another of the genus ''

Schizochytrium ''Schizochytrium'' is a genus of unicellular eukaryotes in the family Thraustochytriaceae, which are found in coastal marine habitats. They are assigned to the Stramenopiles (heterokonts), a group which also contains kelp and various microalgae ...

''. DHA manufactured using microalgae is

vegetarian Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter. Vegetarianism m ...

. In organisms that do not eat

algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...

containing DHA nor animal products containing DHA, DHA is instead produced internally from

α-linolenic acid ''alpha''-Linolenic acid (ALA), also known as α-Linolenic acid (from Greek language, Greek ''alpha'' meaning "first" and ''linon'' meaning flax), is an omega-3 fatty acid, ''n''−3, or omega-3, essential fatty acid. ALA is found in many seeds ...

, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants). Limited amounts of eicosapentaenoic and

docosapentaenoic acid Docosapentaenoic acid (DPA) designates any straight chain 22:5 fatty acid, that is a straight chain open chain type of polyunsaturated fatty acid (PUFA) which contains 22 carbons and 5 double bonds. DPA is primarily used to designate two isomers, ...

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 phospholipids and the

. Research into the potential role or benefit of DHA in various pathologies is ongoing, with significant focus on its mechanism in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and cardiovascular disease.

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 Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...

s (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of a

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

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 Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

s, and the response of rhodopsin contained in the

synaptic vesicle In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulse ...

Phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via ap ...

(PS) – which contains high DHA content – has roles in 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.

Metabolic synthesis

In humans, DHA is either obtained from the diet or may be converted in small amounts from

eicosapentaenoic acid Eicosapentaenoic acid (EPA; also icosapentaenoic 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-c ...

(EPA, 20:5, ω-3) via

(DPA, 22:5 ω-3) as an intermediate. This synthesis had been thought to occur through an elongation step followed by the action of Δ4-

desaturase A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond. These desaturases are classified as: * Delta - indicating that the double bond is created at a fixed position from the ...

. It is now considered more likely that DHA is biosynthesized via a C24 intermediate followed by

beta oxidation In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cyc ...

peroxisome A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pero ...

s. Thus, EPA is twice elongated, yielding 24:5 ω-3, then desaturated to 24:6 ω-3, then shortened to DHA (22:6 ω-3) via

. This pathway is known as "Sprecher's shunt". In organisms such as microalgae,

moss Mosses are small, non-vascular flowerless plants in the taxonomic division Bryophyta (, ) '' sensu stricto''. Bryophyta (''sensu lato'', Schimp. 1879) may also refer to the parent group bryophytes, which comprise liverworts, mosses, and hor ...

es and

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

, biosynthesis of DHA usually occurs as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s. One known pathway in these organisms involves: # a desaturation at the sixth carbon of

by a Δ6 desaturase to produce

stearidonic acid Stearidonic acid (SDA: C18 H28 O2; 18: 4, n-3) is an ω-3 fatty acid, sometimes called moroctic acid. It is biosynthesized from alpha-linolenic acid (ALA: C18H30O2; 18:3, n-3) by the enzyme delta-6-desaturase, that removes two hydrogen (H) ato ...

, # elongation of the

by a Δ6 elongase to produce to

eicosatetraenoic acid Eicosatetraenoic acid (ETA) designates any straight chain 20:4 fatty acid. Eicosatetraenoic acid belongs to the family of eicosanoids, molecules synthesized from oxidized polyunsaturated fatty acids (PUFAs) to mediate cell-cell communication. The ei ...

, # desaturation at the fifth carbon of

by a Δ5 desaturase to produce

, # elongation of

by a Δ5 elongase to produce

, and # desaturation at the fourth carbon of

by a Δ4 desaturase to produce DHA.

Metabolism

DHA can be metabolized into DHA-derived

specialized pro-resolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...

(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 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

metabolizes DHA to

epoxydocosapentaenoic acid Epoxide docosapentaenoic acids (epoxydocosapentaenoic acids, EDPs, or EpDPEs) are metabolites of the 22-carbon straight-chain omega-3 fatty acid, docosahexaenoic acid (DHA). Cell types that express certain cytochrome P450 (CYP) epoxygenases metab ...

s (EDPs; primarily 19,20-epoxy-eicosapentaenoic acid isomers .e. 10,11-EDPs.

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. 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.

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 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.

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 The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

and cell signaling properties, particularly in

grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...

and retinal

photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...

outer segments, which are rich in membranes. A

systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...

found that DHA had no significant benefits in improving visual field in individuals with

retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...

Nutrition

Ordinary types of cooked

salmon Salmon () is the common name for several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the family (biology), family Salmonidae, which are native to tributary, tributaries of the ...

contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams. Additional rich seafood sources of DHA include

caviar Caviar (also known as caviare; from fa, خاویار, khâvyâr, egg-bearing) is a food consisting of salt-cured roe of the family Acipenseridae. Caviar is considered a delicacy and is eaten as a garnish or a spread. Traditionally, the te ...

(3400 mg per 100 grams),

anchovies An anchovy is a small, common forage fish of the family Engraulidae. Most species are found in marine waters, but several will enter brackish water, and some in South America are restricted to fresh water. More than 140 species are placed in 1 ...

(1292 mg per 100 grams),

mackerel Mackerel is a common name applied to a number of different species of pelagic fish, mostly from the family Scombridae. They are found in both temperate and tropical seas, mostly living along the coast or offshore in the oceanic environment. ...

(1195 mg per 100 grams), and cooked

herring Herring are forage fish, mostly belonging to the family of Clupeidae. Herring often move in large schools around fishing banks and near the coast, found particularly in shallow, temperate waters of the North Pacific and North Atlantic Oceans, i ...

(1105 mg per 100 grams).

Brains A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

from mammals are also a good direct source. Beef brain, for example, contains approximately 855 mg of DHA per 100 grams in a serving.

Discovery of algae-based DHA

In the early 1980s,

NASA The National Aeronautics and Space Administration (NASA ) is an independent agency of the US federal government responsible for the civil space program, aeronautics research, and space research. NASA was established in 1958, succeeding t ...

sponsored scientific research on a plant-based food source that could generate oxygen and nutrition on long-duration

space flight Spaceflight (or space flight) is an application of astronautics to fly spacecraft into or through outer space, either with or without humans on board. Most spaceflight is uncrewed and conducted mainly with spacecraft such as satellites in ...

s. Certain species of marine

produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA and arachidonic acid.

Use as a food additive

DHA is widely used as a

food supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

. It was first used primarily in infant formulas. In 2019, the US Food and Drug Administration published qualified

health claim A health claim on a food label and in food marketing is a claim by a manufacturer of food products that their food will reduce the risk of developing a disease or condition. For example, it is claimed by the manufacturers of oat cereals that oat ...

s for DHA. Some manufactured DHA is a

product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3s such as

EPA The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...

. Both fish oil and DHA are odorless and tasteless after processing as a food additive.

Studies of vegetarians and vegans

Vegetarian Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter. Vegetarianism m ...

diets typically contain limited amounts of DHA, and

vegan Veganism is the practice of abstaining from the use of animal product—particularly in diet—and an associated philosophy that rejects the commodity status of animals. An individual who follows the diet or philosophy is known as a vegan. ...

diets typically contain no DHA. In preliminary research, algae-based 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 developing

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

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 Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

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.

Hypothesized role in human evolution

An abundance of DHA in

seafood Seafood is any form of sea life regarded as food by humans, prominently including fish and shellfish. Shellfish include various species of molluscs (e.g. bivalve molluscs such as clams, oysters and mussels, and cephalopods such as octopus an ...

has been suggested as being helpful in the development of a large brain, though other researchers claim a terrestrial diet could also have provided the necessary DHA.

References

{{DEFAULTSORT:Docosahexaenoic Acid Fatty acids Alkenoic acids Polyenes