Docosahexaenoic acid

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Docosahexaenoic acid
IUPAC name (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-
 4,7,10,13,16,19-hexaenoic acid
Other names cervonic acid, DHA
Identifiers
CAS number 6217-54-5
PubChem 445580
SMILES CCC=CCC=CCC=CCC= CCC=CCC=CCCC(=O)O
CC/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
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Docosahexaenoic acid (commonly known as DHA; 22:6(ω-3), all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid; trivial name cervonic acid) is an omega-3 essential 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]

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] 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 chia, flax, and many other seeds and nuts.

DHA is metabolized to form the docosanoids—several families of potent hormones. DHA is a major fatty acid in sperm and brain phospholipids, and especially 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 result in reduction of brain serotonin levels[4] and have been associated with ADHD, Alzheimer's disease, and 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).

Contents

[edit] Central nervous system constituent

DHA is the most abundant essential 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.[5]

Of all the fatty acids, DHA has the largest effect on brain PUFA composition.[6] 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.[7]

DHA deficiency is associated with cognitive decline.[8] PS controls apoptosis, and low DHA levels lower neural cell PS and increase neural cell death.[9] DHA is depleted in the cerebral cortex of severely depressed patients.[10][11]

[edit] 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 is done with an elongation step followed by the action of Δ4-desaturase. Another pathway has also been described in peroxysomes and mitochondria. 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.[12][13]

[edit] Health

[edit] Alzheimer's Disease

A large NIH drug trial is currently recruiting patients for evaluating DHA in Alzheimer's disease.[14] 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.

[edit] 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 linoleic acid), high-fat with corn oil (omega-6 linoleic acid), high-fat with fish oil (omega-3 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 tumors 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.[15]

[edit] 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,[16] 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.[17]

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 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 formula 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.[18][3]

[edit] Nutrition

[edit] 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.[19]

[edit] Algae-derived DHA in infant nutrition

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A study[20] 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.

[edit] 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.[21] Since DHA is made by algae, there are vegan DHA supplements available.


[edit] See also

[edit] Notes and references

  1. ^ docosa- is Greek for 22
  2. ^ The omega end is the one furthest from the carboxyl group.
  3. ^ a b Martek Biosciences Corporation (5 April 2007). History of Martek. Retrieved on March 10, 2007.
  4. ^ Cambridge Applied Polymers Ltd. (4 April 2006). Latest Publications on the Link between DHA and Intelligence / The Brain.. Retrieved on April 4, 2006.
  5. ^ Meharban Singh (March, 2005). Essential Fatty Acids, DHA and the Human Brain from the Indian Journal of Pediatrics, Volume 72. Retrieved on October 8, 2007.
  6. ^ Youdim KA, Martin A, Joseph JA (2000). Essential fatty acids and the brain: possible health implications.. Retrieved on October 8, 2007.
  7. ^ Arthur A. Spector (1999). Essentiality of Fatty Acids from Lipids, Vol. 34. Retrieved on October 8, 2007.
  8. ^ Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. pmid=16151530 (2005 Oct). "A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease.". J Clin Invest. 115(10): 2774-83. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ DHA Deficit Detected in Frontal Cortex of Severely Depressed Patients (September 2007). Retrieved on 2007-10-31.
  12. ^ De Caterina, R and Basta, G (June, 2001). n-3 Fatty acids and the inflammatory response – biological background. Retrieved on February 10, 2006.
  13. ^ Voss, M Reinhart, S Sankarappa and H Sprecher (September, 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. Retrieved on September 23, 2006.
  14. ^ National Institute on Aging (July 16, 2007). DHA Phase 3 trial in Alzheimer's disease. Retrieved on August 10, 2007.
  15. ^ Martek Biosciences's DHA Shown To Inhibit Human Colon Carcinoma In Mice..
  16. ^ Beth Vincent, MHS (2005-10-31). The Importance of DHA During Pregnancy and Breastfeeding. Retrieved on 2007-10-29.
  17. ^ Jennifer Denomme, Ken D. Stark, and Bruce J. Holub (August 20). Directly Quantitated Dietary (n-3) Fatty Acid Intakes of Pregnant Canadian Women Are Lower than Current Dietary Recommendations. Retrieved on October 9, 2007.
  18. ^ Connell, Gary, J. et al (2001-07-26). SOLVENTLESS EXTRACTION PROCESS. Retrieved on February 8, 2006. A patent at the WIPO.
  19. ^ Rivlin, Gary. "Magical or Overrated? A Food Additive in a Swirl", New York Times, 2007-01-14. Retrieved on 2007-01-15. 
  20. ^ 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. 
  21. ^ Muskiet F, Fokkema M, Schaafsma A, Boersma E, Crawford M (2004). "Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials". J Nutr 134 (1): 183-6. PMID 14704315. 
v • d • e
Lipids: fatty acids
Saturated
n−3 Unsaturated
α-Linolenic • Stearidonic • Eicosapentaenoic • Docosahexaenoic
n−6 Unsaturated
n−9 Unsaturated