Docosahexaenoic acid
   HOME

TheInfoList



OR:

Docosahexaenoic acid (DHA) is an omega−3 fatty acid that is an important component of the human
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
,
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. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
,
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 animal coverings, such as the arthropod exoskeleton, have different ...
, and
retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...
. It is given the fatty acid notation 22:6(''n''−3). It can be synthesized from 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 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). Structurally, DHA is a
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
(-''oic acid'') with a 22- carbon chain (''docosa-'' derives from the
Ancient Greek Ancient Greek (, ; ) includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Greek ...
for 22) and six (''hexa-'') '' cis''
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 betw ...
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 languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
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 semitrivi ...
is ''all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid''. In organisms that do not eat
algae Algae ( , ; : alga ) is an informal term for any organisms of a large and diverse group of photosynthesis, photosynthetic organisms that are not plants, and includes species from multiple distinct clades. Such organisms range from unicellular ...
containing DHA nor animal products containing DHA, DHA is instead produced internally from
α-linolenic acid α-Linolenic acid, also known as ''alpha''-linolenic acid (ALA) (from Greek ''alpha'' denoting "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, ...
, 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 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 (i.e. ...
s are possible products of α-linolenic acid metabolism in young women and men. DHA in
breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by the mammary glands in the breasts of women. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a var ...
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 Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s and the
retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...
. Preliminary research has investigated its potential benefit in
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
, and
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
, 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 In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...
s (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of a
neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
al
plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
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 ...
s, and the response of
rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...
contained in the
synaptic vesicle In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are exocytosis, released at the chemical synapse, synapse. The release is regulated by a voltage-dependent calcium channel. Vesicle (biology), Ves ...
s. Phosphatidylserine (PS) – which contains high DHA content – has roles in neuronal signaling and
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
synthesis, and DHA deficiency is associated with cognitive decline. DHA levels are reduced in the brain tissue of severely depressed people.


Biosynthesis


Aerobic eukaryote pathway

Aerobic eukaryotes, specifically microalgae,
moss Mosses are small, non-vascular plant, non-vascular flowerless plants in the taxonomic phylum, division Bryophyta (, ) ''sensu stricto''. Bryophyta (''sensu lato'', Wilhelm Philippe Schimper, Schimp. 1879) may also refer to the parent group bryo ...
es,
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
, 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 An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s. This pathway, originally identified in ''Thraustochytrium'', applies to these groups: # a desaturation at the sixth carbon of 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 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 (i.e. ...
(DPA, 22:5 ω-3), and # desaturation at the fourth carbon of
docosapentaenoic acid 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 (i.e. ...
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 follow the same synthesis pathway as aerobic eukaryotes, 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 biochemistry and metabolism, beta oxidation (also β-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. Acetyl-CoA enter ...
in the
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 perox ...
. The hypothesis was accepted in the absence of an identified Δ4-desaturase in mammals prior to 2015. The shunt model does not match clinical data, specifically that patients with beta oxidation defects do not display issues in DHA synthesis. With the identification of a Δ4-desaturase, it is considered outdated.


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


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 or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
and
cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
properties, particularly in grey matter 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 radiation ...
outer segments, which are rich in membranes. A
systematic review A systematic review is a 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 published studies on ...
found that DHA had no significant benefits in improving visual field in individuals with retinitis pigmentosa. Animal research shows effect of oral intake of deuterium-reinforced DHA (D-DHA) for prevention of
macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no sym ...
.


Asthma

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


Nutrition

Ordinary types of cooked
salmon Salmon (; : salmon) are any of several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the genera ''Salmo'' and ''Oncorhynchus'' of the family (biology), family Salmonidae, native ...
contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams. Additional rich seafood sources of DHA include
caviar Caviar or caviare is a food consisting of salt-cured roe of the family Acipenseridae. Caviar is considered a delicacy and is eaten as a garnish or spread. Traditionally, the term caviar refers only to roe from wild sturgeon in the Caspi ...
(3400 mg per 100 grams), anchovies (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 various species of forage fish, belonging to the Order (biology), order Clupeiformes. Herring often move in large Shoaling and schooling, schools around fishing banks and near the coast, found particularly in shallow, temperate wate ...
(1105 mg per 100 grams). 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. 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.


Discovery of algae-based DHA

In the early 1980s,
NASA The National Aeronautics and Space Administration (NASA ) is an independent agencies of the United States government, independent agency of the federal government of the United States, US federal government responsible for the United States ...
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 objects, usually spacecraft, into or through outer space, either with or without humans on board. Most spaceflight is uncrewed and conducted mainly with spacecraft such a ...
s. Certain species of marine
algae Algae ( , ; : alga ) is an informal term for any organisms of a large and diverse group of photosynthesis, photosynthetic organisms that are not plants, and includes species from multiple distinct clades. Such organisms range from unicellular ...
produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA and
arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...
.


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 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 oa ...
s for DHA. Some manufactured DHA is a
vegetarian Vegetarianism is the practice of abstaining from the Eating, consumption of meat (red meat, poultry, seafood, insects as food, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slau ...
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.


Studies of vegetarians and vegans

Vegetarian Vegetarianism is the practice of abstaining from the Eating, consumption of meat (red meat, poultry, seafood, insects as food, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slau ...
diets typically contain limited amounts of DHA, and
vegan Veganism is the practice of abstaining from the use of animal products and the consumption of animal source foods, and an associated philosophy that rejects the commodity status of animals. A person who practices veganism is known as a ve ...
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 Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by the mammary glands in the breasts of women. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a var ...
levels remain a concern for supplying adequate DHA to the infant.


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


Recommended daily DHA intake for children

As optimal DHA level is important for brain development and maturation, there are established daily recommendations for DHA intake in children. The table below shows the daily DHA / DHA + EPA intake recommended for children of different ages: 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.


See also

* DHA-clozapine * List of omega−3 fatty acids *
Polyunsaturated fatty acid In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...
s


References

{{DEFAULTSORT:Docosahexaenoic Acid Fatty acids Alkenoic acids Polyenes