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Docosahexaenoic acid

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Docosahexaenoic acid
Names
IUPAC name
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid; Doconexent
Other names
cervonic acid, DHA
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.118.398 Edit this at Wikidata
UNII
  • InChI=1/C22H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24/h3-4,6-7,9-10,12-13,15-16,18-19H,2,5,8,11,14,17,20-21H2,1H3,(H,23,24)/b4-3-,7-6-,10-9-,13-12-,16-15-,19-18-
    Key: MBMBGCFOFBJSGT-KUBAVDMBBZ
  • O=C(O)CC\C=C/C/C=C\C\C=C/C\C=C/C\C=C/C\C=C/CC
Properties
C22H32O2
Molar mass 328.488 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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 complex organisms with access to oceanic foods 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] Some animals with access to seafood make very little DHA through metabolism, but obtain it in the diet. However, in strict herbivores, and carnivores that do not eat seafood, DHA is manufactured internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants).

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 in the brain and retina. DHA comprises 40% of the polyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. 50% of the weight of a 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 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.

The NIA trial lasted 18 months and was conducted in people with mild to moderate Alzheimer's.Researchers from the National Institute on Aging (NIA)-supported Alzheimer's Disease Cooperative Study (ADCS), led by Joseph Quinn, MD, Associate Professor of Neurology at Oregon Health and Sciences University, conducted a double blind, randomized, placebo-controlled clinical trial comparing DHA and placebo in 402 people (average age=76) diagnosed with mild to moderate Alzheimer's at 51 sites in the U.S. According to the researchers, treatment with DHA clearly increased blood levels of DHA, and also appeared to increase brain DHA levels, based on a measured increase of DHA in study participants' cerebrospinal fluid (CSF).

However, DHA treatment did not slow the rate of change on tests of mental function (ADAS-cog), global dementia severity status (CDR-SOB), activities of daily living (ADL), or behavioral symptoms (NPI) in the study population as a whole. There was no different treatment effect between the mild and moderate Alzheimer's patients.

"These trial results do not support the routine use of DHA for patients with Alzheimer's," Quinn said.

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]

DHASCO[20] 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 DHASCO and ARASCO (arachidonic acid single cell organism) to its Enfamil Lipil product, received a "Generally Regarded As Safe"status by the Food and Drug Administration and Health Canada.

DHASCO does not make 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][21] There are no scientific review studies showing that DHA additives benefit brain development of term infants, as formula makers claim in their advertisements, which has led some public interest groups to file complaints with the Federal Trade Commission of the United States, alleging false and misleading advertising.[22]

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 DHASCO-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. [citation needed] 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 DHASCO is a vegetarian product extracted from algae. Both types are odorless and tasteless after processing.[23]

Algae-derived DHA in infant nutrition

A study[24] found that preterm infants fed baby formulas fortified with DHASCO provided better developmental outcomes than formulas not containing the supplement.

Studies of vegetarians and vegans

Main article: Vegetarian nutrition § Omega-3 fatty acids

Vegetarian diets typically contain limited amounts of DHA, and vegan diets typically contain no DHA. Vegetarians and vegans have substantially lower levels of DHA in their body, and short-term supplemental ALA has been shown to increase EPA but not DHA. However, supplemental preformed DHA, available in algae-derived oils or capsules, has been shown to increase DHA levels. While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans, fetal and breast milk levels remain a concern.[25]

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.[26]

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,[27] though other researchers claim a terrestrial diet could also have provided the necessary docosahexaenoic acid.[28]

See also

Notes and references

  1. ^ docosa- is Greek for 22
  2. ^ The omega end is the one furthest from the carboxyl group.
  3. ^ a b c Martek Biosciences Corporation (5 April 2007). "History of Martek". Archived from the original on February 5, 2007. Retrieved March 10, 2007. Cite error: The named reference "Martek" was defined multiple times with different content (see the help page).
  4. ^ Meharban Singh (2005). "Essential Fatty Acids, DHA and the Human Brain from the Indian Journal of Pediatrics, Volume 72" (PDF). Retrieved October 8, 2007. {{cite web}}: Unknown parameter |month= ignored (help)
  5. ^ Youdim KA, Martin A, Joseph JA (2000). "Essential fatty acids and the brain: possible health implications". Retrieved October 8, 2007.{{cite web}}: CS1 maint: multiple names: authors list (link)
  6. ^ Arthur A. Spector (1999). "Essentiality of Fatty Acids from Lipids, Vol. 34". Retrieved October 8, 2007.
  7. ^ Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. pmid=16151530 (2005 October). "A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease". J Clin Invest. 115 (10): 2774–83. doi:10.1172/JCI25420. PMC 1199531. PMID 16151530. {{cite journal}}: Check date values in: |year= (help); Missing pipe in: |author= (help); line feed character in |author= at position 90 (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) CS1 maint: year (link)
  8. ^ Serhan CN, Gotlinger K, Hong S, Arita M (2004). "Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis". Prostaglandins Other Lipid Mediat. 73 (3–4): 155–72. doi:10.1016/j.prostaglandins.2004.03.005. PMID 15290791.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ McNamara RK, Hahn CG, Jandacek R; et al. (2007). "Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder". Biol. Psychiatry. 62 (1): 17–24. doi:10.1016/j.biopsych.2006.08.026. PMID 17188654. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  10. ^ "DHA Deficit Detected in Frontal Cortex of Severely Depressed Patients". Fats of Life. 2007. Retrieved 2007-10-31. {{cite journal}}: Unknown parameter |month= ignored (help)
  11. ^ De Caterina, R and Basta, G (2001). "n-3 Fatty acids and the inflammatory response – biological background" (PDF). Retrieved February 10, 2006. {{cite web}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Voss, M Reinhart, S Sankarappa and H Sprecher (1991). "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" (PDF). Retrieved September 23, 2006. {{cite web}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ National Institute on Aging (July 16, 2007). "DHA Phase 3 trial in Alzheimer's disease". Retrieved August 10, 2007.
  14. ^ Kato T, Hancock RL, Mohammadpour H, McGregor B, Manalo P, Khaiboullina S, Hall MR, Pardini L, Pardini RS (2002). "Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice". Cancer Lett. 187 (1–2): 169–77. doi:10.1016/S0304-3835(02)00432-9. PMID 12359365.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Schønberg SA, Lundemo AG, Fladvad T, Holmgren K, Bremseth H, Nilsen A, Gederaas O, Tvedt KE, Egeberg KW, Krokan HE (2006). "Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element-binding protein 1". Cancer Lett. 273 (12): 2749–65. doi:10.1111/j.1742-4658.2006.05292.x. PMID 16817902.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Shaikh IAA, Brown I, Schofield AC, Wahle KWJ, Heys SD (2008). "Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: the role of genes associated with the NF-kappaB pathway". Prostate. 68 (15): 1635–1646. doi:10.1002/pros.20830. PMID 18668525. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Elmesery ME, Algayyar MM, Salem HA, Darweish MM, El-Mowafy AM (2009). "Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides". Cell Div. 4 (1): 6. doi:10.1186/1747-1028-4-6. PMC 2680397. PMID 19341447. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  18. ^ Beth Vincent, MHS (2005-10-31). "The Importance of DHA During Pregnancy and Breastfeeding". Archived from the original on 2007-11-17. Retrieved 2007-10-29.
  19. ^ Jennifer Denomme, Ken D. Stark, and Bruce J. Holub (August 20, 2004). "Directly Quantitated Dietary (n-3) Fatty Acid Intakes of Pregnant Canadian Women Are Lower than Current Dietary Recommendations". Retrieved October 9, 2007.{{cite web}}: CS1 maint: multiple names: authors list (link)
  20. ^ DHASCO and ARASCO in Infant Formula - Food Standards
  21. ^ Connell, Gary, J.; et al. (2001-07-26). "SOLVENTLESS EXTRACTION PROCESS". Retrieved February 8, 2006. {{cite web}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) A patent at the WIPO.
  22. ^ Replacing Mother—Imitating Human Breast Milk in the Laboratory. The Cornucopia Institute. January 2008
  23. ^ Rivlin, Gary (2007-01-14). "Magical or Overrated? A Food Additive in a Swirl". The New York Times. Retrieved 2007-01-15.
  24. ^ Clandinin M, Van Aerde J, Merkel K, Harris C, Springer M, Hansen J, Diersen-Schade D (2005). "Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid". J Pediatr. 146 (4): 461–8. doi:10.1016/j.jpeds.2004.11.030. PMID 15812447.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Sanders, Thomas A.B. (August–September 2009). "DHA status of vegetarians". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 81 (2–3). International Society for the Study of Fatty Acids and Lipids: 137–141. doi:10.1016/j.plefa.2009.05.013. ISSN 0952-3278. PMID 19500961. {{cite journal}}: |access-date= requires |url= (help)
  26. ^ Vedin I; et al. (1 June 2008title=Effects of docosahexaenoic acid–rich n–3 fatty acid supplementation on cytokine release). "Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study". Am J Clin Nutr. 87 (6): 1616–1622. PMID 18541548. {{cite journal}}: Check date values in: |date= (help); Explicit use of et al. in: |author= (help)
  27. ^ Crawford, M; et al. (2000). "Evidence for the unique function of docosahexanoic acid (DHA) during the evolution of the modern hominid brain". Lipids. 34: S39 – S47. doi:10.1007/BF02562227. PMID 10419087. {{cite journal}}: Explicit use of et al. in: |author= (help)
  28. ^ Carlson BA, Kingston JD (2007). "Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization without aquatic constraint". Am. J. Hum. Biol. 19 (4): 585–8. doi:10.1002/ajhb.20683. PMID 17546613.
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