Docosahexaenoic acid
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2008-07-14T19:27:40Z
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{{Chembox new
| Name = Docosahexaenoic acid
| ImageFile = DHAnumbering.png
| ImageSize = 450px
| OtherNames = cervonic acid, DHA
| IUPACName = (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-<br /> 4,7,10,13,16,19-hexaenoic acid
| Section1 = {{Chembox Identifiers
| CASOther = 6217-54-5| PubChem =445580
| SMILES = CCC=CCC=CCC=CCC= CCC=CCC=CCCC(=O)O<br>CC/C=C\C/C=C\C/C=C\C/C= C\C/C=C\C/C=C\CCC(=O)O
}}
| Section2 = {{Chembox Properties
| Formula = C<sub>22</sub>H<sub>32</sub>O<sub>2</sub>.
| MolarMass = 328.488 g/mol
}}
}}
'''Docosahexaenoic acid''' (commonly known as '''[[DHA]]'''; 22:6(ω-3), ''all-cis''-docosa-4,7,10,13,16,19-hexa-[[alkene|en]]oic acid; [[trivial name]] '''cervonic acid''') is an [[omega-3 fatty acid|omega-3]] [[essential fatty acid]]. In chemical structure, DHA is a [[carboxylic acid]] with a 22-[[carbon chain]]<ref>''docosa-'' is [[Greek]] for 22</ref> and [[hexa|six]] ''[[Cis-trans isomerism|cis]]'' [[double bond]]s; the first double bond is located at the third carbon from the omega end.<ref>The omega end is the one furthest from the [[carboxyl group]].</ref>
[[Fish oil]]s 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]]''.<ref name=Martek>{{cite web|url=http://aboutmartek.martek.com/history/ |author=Martek Biosciences Corporation |title=History of Martek |date=[[5 April]] [[2007]]|accessmonthday=March 10 |accessyear=2007}}</ref> Most animals make very little DHA through metabolism; however small amounts are manufactured internally through the consumption of [[Alpha-linolenic acid|α-linolenic acid]], an omega-3 fatty acid found in [[chia]], [[flaxseed|flax]], and many other seeds and nuts.
DHA is metabolized to form the [[docosanoid]]s—several families of potent hormones.
DHA is a major fatty acid in sperm and brain [[phospholipid]]s, and especially in the retina. Dietary DHA may reduce the risk of [[heart disease]] by reducing the level of [[blood]] [[triglyceride]]s in humans. Low levels of DHA result in reduction of brain [[serotonin]] levels<ref name=Cambridge>{{cite web| url= http://www.cambridgeappliedpolymers.com/industry_news/latest_publications_on_omega-3_dha_and_intelligence.html |author=Cambridge Applied Polymers Ltd.|title=Latest Publications on the Link between DHA and Intelligence / The Brain. |date=[[4 April]] [[2006]]|accessmonthday=April 4 |accessyear=2006}}</ref> and have been associated with [[attention-deficit hyperactivity disorder|ADHD]], [[Alzheimer's disease]], and [[clinical depression|depression]], among other diseases, and there is mounting evidence that DHA supplementation may be effective in combating such diseases (see external links at the end of this article).
==Central nervous system constituent==
DHA is the most abundant essential fatty acid ([[polyunsaturated fatty acid]]s, 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.<ref name=Singh>{{cite web | author = Meharban Singh | title = Essential Fatty Acids, DHA and the Human Brain from the Indian Journal of Pediatrics, Volume 72 | url = http://medind.nic.in/icb/t05/i3/icbt05i3p239.pdf | accessmonthday = October 8 | accessyear = 2007 | year = March, 2005 |format=PDF}}</ref>
Of all the fatty acids, DHA has the largest effect on brain PUFA composition.<ref name=youdim>{{cite web | author = Youdim KA, Martin A, Joseph JA | title = Essential fatty acids and the brain: possible health implications. | year = 2000 | url = http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10817922 | accessmonthday = October 8 | accessyear = 2007 }}</ref>
DHA is found in three [[phospholipids]]: [[phosphatidylethanolamine]], [[ethanolamine]] [[plasmalogen]]s, and [[phosphatidylserine]] (PS).
It 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, among many other functions.<ref name=Spector>{{cite web | author = Arthur A. Spector | title = Essentiality of Fatty Acids from Lipids, Vol. 34 | year = 1999 | url = http://www.springerlink.com/content/3547007r16268860/ | accessmonthday = October 8 | accessyear = 2007}}</ref>
DHA deficiency is associated with cognitive decline.<ref name=Lukiw>{{cite journal
|journal=J Clin Invest. |year=2005 Oct|volume=115(10)|pages=2774–83
|title= A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease
|author= Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG.
pmid=16151530}}</ref> PS controls [[apoptosis]], and low DHA levels lower neural cell PS and increase neural cell death.<ref name=Serhan2>
{{cite journal |author=Serhan CN, Gotlinger K, Hong S, Arita M |title=Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis |journal=Prostaglandins Other Lipid Mediat. |volume=73 |issue=3-4 |pages=155–72 |year=2004 |pmid=15290791 |doi=10.1016/j.prostaglandins.2004.03.005}}</ref>
DHA is depleted in the cerebral cortex of severely depressed patients.<ref name="pmid17188654">{{cite journal
|author=McNamara RK, Hahn CG, Jandacek R, ''et al''
|title=Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder
|journal=Biol. Psychiatry
|volume=62
|issue=1
|pages=17–24
|year=2007
|pmid=17188654
|doi=10.1016/j.biopsych.2006.08.026
|accessdate=
}}</ref><ref name=fatsoflife>{{cite web
|title=DHA Deficit Detected in Frontal Cortex of Severely Depressed Patients
|date=September 2007
|url= http://fatsoflife.com/pufa/article.asp?nid=1&edition=this&id=493
|journal=Fats of Life
|accessdate=2007-10-31}}</ref>
==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 [[peroxisome]]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 [[beta oxidation]]. This pathway is known as '''Sprecher's shunt'''.<ref name=DeCaterina>{{cite web
|author=De Caterina, R and Basta, G|title= n-3 Fatty acids and the inflammatory response – biological background| url = http://eurheartjsupp.oxfordjournals.org/cgi/reprint/3/suppl_D/D42.pdf|accessmonthday= February 10 |accessyear = 2006|year=June, 2001|format=PDF}}</ref><ref name=Voss>{{cite web|title=The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4- desaturase|author=Voss, M Reinhart, S Sankarappa and H Sprecher |url=http://eurheartjsupp.oxfordjournals.org/cgi/reprint/3/suppl_D/D42.pdf |accessmonthday= September 23 |accessyear=2006|year= September, 1991|format=PDF}}</ref>
==Health==
===Alzheimer's Disease===
A large NIH drug trial is currently recruiting patients for evaluating DHA in Alzheimer's disease.<ref>{{cite web
|title=DHA Phase 3 trial in Alzheimer's disease |author=National Institute on Aging
|year=July 16, 2007 |accessmonthday=August 10 |accessyear=2007
|url=http://clinicaltrials.gov/ct/show/NCT00440050}}</ref> This is the first human trial of DHA. 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===
Researchers at the [[University of Nevada]] conducted a study on the effects of DHA supplementation on the growth of human [[colon]] [[adenocarcinoma]] in mice. The animals received one of four specialized diets: low-fat with corn oil ([[Omega-6 fatty acid|omega-6]] [[linoleic acid]]), high-fat with corn oil (omega-6 linoleic acid), high-fat with fish oil ([[Omega-3 fatty acid|omega-3]] [[Eicosapentaenoic acid|EPA]] and DHA), and high-fat with algae-derived DHA (omega-3 DHA). At completion, the mice receiving a diet supplemented with algae-derived DHA had [[tumor]]s that were smaller than those of mice receiving diets supplemented with omega-3 from fish oil as well as those fed both the high- and low-fat corn oil (omega-6) diets. These results indicate that algae-derived DHA possesses greater tumor-suppressing properties than do corn or fish oil.<ref>{{cite web|title= Martek Biosciences's DHA Shown To Inhibit Human Colon Carcinoma In Mice.|url=http://www.immunesupport.com/library/showarticle.cfm/ID/4154/}}</ref>
===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,<ref name=Vincent>{{cite web|
title=The Importance of DHA During Pregnancy and Breastfeeding|
date=2005-10-31|
author=Beth Vincent, MHS| url=
http://www.drlaura.com/sah/sahm.html?mode=view&tile=1&id=10576|
accessdate=2007-10-29}}</ref> 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 performed 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.<ref name=denomme>{{cite web|title = Directly Quantitated Dietary (n-3) Fatty Acid Intakes of Pregnant Canadian Women Are Lower than Current Dietary Recommendations | author = Jennifer Denomme, Ken D. Stark, and Bruce J. Holub | year = 2004 | date = August 20 | accessmonthday = October 9 | accessyear = 2007 | url = http://jn.nutrition.org/cgi/content/abstract/135/2/206}}</ref>
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 [[Department of Health (Canada)|Health Canada]]. Both DHA and ARA are permitted in infant formula, as both are components of human breast milk. The addition of DHA at dose-effective levels has been shown to improve congitive function in both term and preterm infants.
DHA makes infant formulas more like human milk than "conventional" formula containing [[Alpha-linolenic acid]] and [[linoleic acid]], which are [[wiktionary:Precursor|precursor]]s to DHA. Formula sold in North America uses lipids from microorganisms grown in [[bioreactor]]s as sources of DHA.<ref name=Connell>{{cite web
|author=Connell, Gary, J. ''et al''|title=SOLVENTLESS EXTRACTION PROCESS|year= 2001-07-26
|url= http://www.wipo.int/ipdl/IPDL-CIMAGES/view/pct/getbykey5?KEY=01/53512.010726&ELEMENT_SET=DECL
|accessmonthday=February 8 |accessyear=2006}} A patent at the [[WIPO]].</ref><ref name=Martek>{{cite web|url= http://www.martekbio.com/Nutritional_Products/Introduction.asp|title=Martek DHA and ARA Introduction|accessmonthday=February 9 |accessyear=2006}}</ref>
==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.<ref name=Rivlin>{{cite news
|last= Rivlin | first= Gary |publisher= [[New York Times]]
|title=Magical or Overrated? A Food Additive in a Swirl
| url = http://www.nytimes.com/2007/01/14/business/yourmoney/14omega.html?_r=1&ref=health&oref=slogin
|date=[[2007-01-14]] |accessdate=2007-01-15}}</ref>
===Algae-derived DHA in infant nutrition===
{{POV-section|date=December 2007}}
A study<ref name=Clandinin>{{cite journal |author=Clandinin M, Van Aerde J, Merkel K, Harris C, Springer M, Hansen J, Diersen-Schade D |title=Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid |journal=J Pediatr |volume=146 |issue=4 |pages=461–8 |year=2005 |pmid=15812447 |doi=10.1016/j.jpeds.2004.11.030}}</ref> 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.{{Fact|date=February 2007}} This is especially important for pregnant and nursing women and young children.
===Studies of vegans and vegetarians===
[[Vegan]]s and [[vegetarian]]s 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.<ref name=Muskiet>
{{cite journal |author=Muskiet F, Fokkema M, Schaafsma A, Boersma E, Crawford M |title=Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials |journal=J Nutr |volume=134 |issue=1 |pages=183–6|url=http://jn.nutrition.org/cgi/content/full/134/1/183 |year=2004 |pmid=14704315}}
</ref> Since DHA is made by algae, there are vegan DHA supplements available.
==See also==
* [[Chlorella]]
* [[Cyanobacteria]]
*[[List of omega-3 fatty acids]]
*[[Polyunsaturated fatty acid]]s
==Notes and references==
{{Reflist|2}}
{{Fatty acids}}
[[Category:Fatty acids]]
[[bg:Докозахексаенова киселина]]
[[da:Docosahexaensyre]]
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[[nl:Docosahexaeenzuur]]
[[ja:ドコサヘキサエン酸]]
[[pt:DHA]]
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