Docosahexaenoic acid

Docosahexaenoic acid
IUPAC name	(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid; Doconexent
Other names	cervonic acid, DHA
Identifiers
CAS number	6217-54-5 Y
PubChem	445580
SMILES	CCC=CCC=CCC=CCC= CCC=CCC=CCCC(=O)OCC/C=C\C/C=C\C/C=C\C/C= C\C/C=C\C/C=C\CCC(=O)O
Properties
Molecular formula	C22H32O2.
Molar mass	328.488 g/mol
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Docosahexaenoic acid (DHA) is an omega-3 fatty acid. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain^[1] and six cis double bonds; the first double bond is located at the third carbon from the omega end.^[2] Its trivial name is cervonic acid, its systematic name 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.

Fish oils are rich in DHA. Most of the DHA in fish and more complex organisms originates in photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms as it moves up the food chain. DHA is also commercially manufactured from microalgae; Crypthecodinium cohnii and another of the genus Schizochytrium.^[3] DHA manufactured using microalgae is vegetarian.^[3] Most animals make very little DHA through metabolism; however small amounts are manufactured internally through the consumption of α-linolenic acid, an omega-3 fatty acid found in plants, animals, and milk.

DHA is metabolized to form the docosanoids, which comprise several families of potent hormones. DHA is a major fatty acid in sperm and brain phospholipids, particularly in the retina. Dietary DHA may reduce the risk of heart disease by reducing the level of blood triglycerides in humans. Low levels of DHA have been associated with Alzheimer's disease.

Central nervous system constituent

DHA is the most abundant omega 3 fatty acid (polyunsaturated fatty acids, PUFAs) in the brain and retina. It comprises 40% of the PUFAs in the brain and 60% of the PUFAs in the retina. 50% of the weight of the neuron's plasma membrane is composed of DHA.^[4]

Of all the fatty acids, DHA has the largest effect on brain PUFA composition.^[5] DHA is found in three phospholipids: phosphatidylethanolamine, ethanolamine plasmalogens, and phosphatidylserine (PS). It 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, among many other functions.^[6]

DHA deficiency is associated with cognitive decline.^[7] PS controls apoptosis, and low DHA levels lower neural cell PS and increase neural cell death.^[8] DHA is depleted in the cerebral cortex of severely depressed patients.^[9][10]

Metabolic synthesis

In the human body, DHA is either present in the diet or it is derived from eicosapentaenoic acid (EPA, 20:5, ω-3) via docosapentaenoic acid (DPA, 22:5 ω-3) as an intermediate. This had been thought to occur through an elongation step followed by the action of Δ4-desaturase. It is now more likely that DHA is biosynthesized via a C24 intermediate followed by beta oxidation in peroxisomes. 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 beta oxidation. This pathway is known as Sprecher's shunt.^[11][12]

Health

Alzheimer's Disease

A large NIH (US National Institutes of Health) intervention trial is currently running to evaluate DHA in Alzheimer's disease.^[13] This is the first large scale human trial of DHA and Alzheimer's disease. Animal studies in the TG3 transgenic mouse model of Alzheimer's disease linked decreases in amyloid plaques and tau to dietary DHA. Animal studies also show that when combined with arachidonic acid (also present in fish oil), the effectiveness of DHA for preventing plaques was less than without it.

Cancer

DHA was found to inhibit growth of human colon carcinoma cells^[14][15], more than other omega-3 PUFAs. The cytotoxic effect of DHA wasn't caused by increased lipid peroxidation or any other oxidative damage, but rather decrease in cell growth regulators. However, different cancer lines handle PUFAs differently and display different sensitivities towards them. Such preliminary findings point to the need for further research and are not proof that DHA does or does not provide any benefit for intended treatment, cure, or mitigation of cancer. However, in 2008, DHA was shown to increase the efficacy of chemotherapy in prostate cancer cells,^[16] and in 2009, a chemoprotective effect in a mouse model was reported.^[17]

Pregnancy and lactation

DHA concentrations in breast milk range from 0.07% to greater than 1.0% of total fatty acids, with a mean of about 0.34%. DHA levels in breast milk are higher if a mother's diet is high in fish.

DHA has recently gained attention as a supplement for pregnant women,^[18] noting studies of improved attention and visual acuity. One recent study indicates that low levels of plasma and erythrocyte DHA were associated with poor retinal development, low visual acuity, and poor cognitive development. In that same study, alpha-linolenic acid was shown as a source of fetal DHA, but that preformed DHA was more readily accredited. A working group from the ISSFAL (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. Other requirements are available from other sources.^[19]

DHA has been an ingredient in several brands of premium infant formula sold in North America since 2001 after Mead Johnson, the first infant formula manufacturer to add DHA and ARA (arachidonic acid) to its Enfamil Lipil product, received approval by the Food and Drug Administration and Health Canada. Both DHA and ARA, manufactured by Martek Biosciences Corporation, are permitted in infant formula.

DHA makes infant formulas more like human milk than "conventional" formula containing Alpha-linolenic acid and linoleic acid, which are precursors to DHA. Formula sold in North America uses lipids from microorganisms grown in bioreactors as sources of DHA.^[3][20]

Nutrition

Promotion as a food additive

DHA is actively promoted by manufacturers as a food additive. Until recently, sales other than to makers of infant formula have been minimal; however, in 2007, several DHA-fortified dairy items (milk, yogurt) began selling in grocery stores.

There is less DHA available in the average diet than formerly, due to cattle being taken off grass and fed grain before butchering; likewise, there is less in eggs due to intensive farming. DHA is widely believed to be helpful to people with a history of heart disease, for premature infants, and to support healthy brain development especially in young children. Some manufactured DHA is a vegetarian product extracted from algae. Both types are odorless and tasteless after processing.^[21]

Algae-derived DHA in infant nutrition

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A study^[22] found that preterm infants fed baby formulas fortified with DHA derived directly from algae gained weight faster than infants fed formula fortified with DHA from fish oil. In addition, there are no risks of harmful contaminants such as methyl mercury or dioxins, which may be present in fish and fish oils.^{[citation needed]} This is especially important for pregnant and nursing women and young children.

Studies of vegans and vegetarians

Vegans and vegetarians have markedly lower stores of DHA. Their bodily DHA levels do not rise much even with high dietary levels of linolenic acid. This, and features of the production and distribution of DHA in pregnant and lactating women, indicates that DHA per se is an essential nutrient.^[23] Since DHA is made by algae, there are vegan DHA supplements available.

DHA and EPA in fish oils

Fish oil is widely sold in gelatin capsules containing a mixture of omega-3 fatty acids including EPA and smaller quantities of DHA. Researchers have found that fish oil high in DHA and low in EPA lowered inflammatory cytokines, such as IL-6 and IL-1β, associated with neurodegenerative and autoimmune diseases. They note that the brain normally contains DHA but no EPA.^[24]

Hypothesized role in evolution

It has been suggested that the abundance of docosahexaenoic acid in seafood would have been helpful in the development of a large brain,^[25] though other researchers claim a terrestrial diet could also have provided the necessary docosahexaenoic acid.^[26]

See also

• Chlorella
• Cyanobacteria
• List of omega-3 fatty acids
• Polyunsaturated fatty acids
• Eicosapentaenoic acid (EPA)

Notes and references

External links

• Docosahexaenoic acid (DHA) – University of Maryland Medical Center (UMMC)