Docosahexaenoic acid

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Docosahexaenoic acid
DHA numbers.svg
Docosahexaenoic-acid-3D-balls.png Docosahexaenoic-acid-3D-sf.png
Identifiers
CAS number 6217-54-5 YesY
PubChem 445580
ChemSpider 393183 YesY
UNII ZAD9OKH9JC YesY
ChEBI CHEBI:28125 YesY
ChEMBL CHEMBL367149 YesY
Jmol-3D images Image 1
Properties
Molecular formula C22H32O2
Molar mass 328.488 g/mol
Density 0.943 g/cm3
Melting point −44 °C (−47 °F; 229 K)
Boiling point 446.7 °C (836.1 °F; 719.8 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk or fish oil.[1] DHA's structure is a carboxylic acid (-oic acid) with a 22-carbon chain (docosa- is Greek for 22) and six (hexa-) cis double bonds (-en-);[2] with the first double bond located at the third carbon from the omega end.[3] 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.

Cold-water oceanic fish oils are rich in DHA. Most of the DHA in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms the further they are up the food chain. DHA is also commercially manufactured from microalgae: Crypthecodinium cohnii and another of the genus Schizochytrium.[4] DHA manufactured using microalgae is vegetarian.[4]

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). Limited amounts of eicosapentaenoic and docosapentaenoic acids are possible products of α-linolenic acid metabolism in young women[5] and men,[6] and though DHA is difficult to detect above dietary background in males compared with females, this illustrates the importance of DHA production for the developing fetus and healthy breast milk.[7] Rates of conversion are 15% higher for women, with those taking oral contraceptives demonstrating 10% higher DHA levels.[8] Administration of testosterone or the aromatase inhibitor anastrozole, which blocks conversion of testosterone to estradiol, reduces DHA conversion.[8] DHA is a major fatty acid in sperm and brain phospholipids and in the retina. Dietary DHA may reduce the risk of heart disease by reducing the level of blood triglycerides in humans.[9] Below-normal levels of DHA have been associated with Alzheimer's disease. A low level of DHA is also spotted in patients with retinitis pigmentosa .

Central nervous system constituent[edit]

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. Fifty percent of the weight of a neuron's plasma membrane is composed of DHA.[10] DHA is richly supplied during breastfeeding, and DHA levels are high in breastmilk regardless of dietary choices.

DHA 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.[11]

DHA deficiency is associated with cognitive decline.[12] Phosphatidylserine (PS) controls apoptosis, and low DHA levels lower neural cell PS and increase neural cell death.[13] DHA levels are reduced in the brain tissue of severely depressed patients.[14][15]

Metabolic synthesis[edit]

In humans, DHA is either obtained from the diet or may be converted in small amounts from eicosapentaenoic acid (EPA, 20:5, ω-3) via docosapentaenoic acid (DPA, 22:5 ω-6) as an intermediate.[5][6] This synthesis had been thought to occur through an elongation step followed by the action of Δ4-desaturase.[6] It is now considered 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.[16][17]

Potential health effects[edit]

Alzheimer's disease and decline of mental health[edit]

Preclinical studies indicate that DHA improves memory,[18][19] can slow the progression of Alzheimer's disease neuropathology in mice,[20][21] sparking interest in additional research. However, the first large-scale human trials showed that DHA did not slow decline of mental function in elderly people with mild to moderate Alzheimer's disease.[22] These trials were part of a large US National Institutes of Health (NIH) intervention study to evaluate DHA in Alzheimer's disease.[23]

Researchers from the National Institute on Aging-supported Alzheimer's Disease Cooperative Study conducted a double-blind, randomized, placebo-controlled clinical trial comparing DHA and placebo over 18 months in 402 people (average age=76) diagnosed with mild to moderate Alzheimer's disease.[22] Treatment with DHA increased blood levels of DHA, and appeared to increase brain DHA levels, based on a measured increase of DHA in study participants' cerebrospinal fluid.

However, DHA treatment did not slow the rate of change on tests of mental function, global dementia severity status, activities of daily living, or behavioral symptoms in the study population as a whole. Treatment effects did not differ between the mild and moderate Alzheimer's patients, leading study authors to conclude that the results do not support the routine use of DHA for patients with Alzheimer's.[22]

Animal studies in the various transgenic mouse models of Alzheimer's disease had linked dietary DHA to decreases in amyloid plaques and tau.[24][25] Animal studies also showed, when DHA was combined with arachidonic acid (AA or ARA, also present in fish oil), plaque formation was greater with the arachidonic acid compared to DHA alone.

DHA deficiency likely plays a role in decline of mental function in healthy adults, which is indicated in a study from 2010 conducted at 19 U.S. clinical sites on 485 subjects aged 55 and older who met criteria for age-associated memory impairment. The study found algal DHA taken for six months decreased heart rate and improved memory and learning in healthy, older adults with mild memory complaints. These findings indicate the importance of early DHA intervention and provided a statistically significant benefit to cognitive function in individuals over 50 years of age.[26][26]

Higher DHA levels in middle-aged adults is related to better performance on tests of nonverbal reasoning and mental flexibility, working memory, and vocabulary.[27] DHA is the majority component of a Souvenaid, an oral supplement developed by MIT scientists that has been shown to modestly improve memory in subjects with early Alzheimer’s disease while showing insignificant benefits in other tests of cognitive function.[28][29]

The use of DHA by persons with epilepsy could decrease the frequency of their seizures. Studies have shown that children with epilepsy had a major improvement, i.e. decrease in the frequency of their seizures,[citation needed] but another study showed mixed results with 57 adults taking DHA supplementation. The 57 subjects demonstrated a decreased frequency of seizures for the first six weeks of the study, but for some it was just a temporary improvement.[30]

Cancer[edit]

In mice, DHA was found to inhibit growth of human colon carcinoma cells,[31][32] more than other omega-3 PUFAs. The cytotoxic effect of DHA was not caused by increased lipid peroxidation or any other oxidative damage, but rather a decrease in cell growth regulators. However, different cancer lines may handle PUFAs differently and display different sensitivities toward them.[citation needed]

DHA was shown to increase the efficacy of chemotherapy in prostate cancer cells in vitro,[33] and a chemoprotective effect in a mouse model was reported.[34] By contrast, one case-control study nested within a clinical trial originally designed to test the effect of finasteride on prostate cancer occurrence, the "Prostate Cancer Prevention Trial", found that DHA measured in blood serum was associated with an increase in high-grade prostate cancer risk.[35] In addition to DHA's possible anticancer effect, it may also be used as a non-toxic adjuvant to increase the efficacy of chemotherapy.[36]

Pregnancy and lactation[edit]

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. The Food and Drug Administration has noted specific concerns for women who are pregnant or might become pregnant, nursing mothers, and young children regarding mercury levels in fish and shellfish.[37]

DHA has recently gained attention as a supplement for pregnant women, noting studies of improved attention and visual acuity. Given the recently gained attention, the majority of pregnant women in the U.S. fail to get the recommended amount of DHA in their diets.[38] One recent study indicated 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 preformed DHA was more readily accredited.[citation needed] 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. The March of Dimes Foundation recommends pregnant women consume at least 200 mg DHA per day.[39] Other requirements are available from other sources.[40]

Docosahexaenoic acid single-cell oil (DHASCO)[41][42] 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 arachidonic acid single-cell organism oil to its Enfamil Lipil product, received a "Generally Regarded As Safe" status by the Food and Drug Administration and Health Canada. Several past and recent studies indicate supplementation with arachidonic acid (omega-6) may be unsuitable for some infants and toddlers as it may potentiate the inflammatory response.[43]

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.[4][44] Some doubt 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.[45] There is some obvious debate about the safety of single cell DHA and AA as compared to natural sources, but original studies on the increase of the Mental Development Index were based on single cell DHA and AA added to preformed Enfamil.[46] The following is a good review of that study: "The study tested the intelligence scores of 56 infants, 18 months old. One group received formula containing only DHA, while another received one containing DHA and AA. The control group's commercial formula did not contain either substance. All three groups of infants were enrolled in the study within five days of their birth, and for 17 weeks received one of the three formulas.

When the children's overall intelligence was tested, they differed significantly on the Mental Development Index (MDI) that measures young children's memory, their ability to solve simple problems, and their language capabilities.

The children in the control group received an average MDI score of 98 – slightly below the national average of 100 for U.S. children. The DHA group received an average score of 102.4, and the DHA plus AA group received an average score of 105." [47]

A study[48] found that preterm infants fed baby formulas fortified with DHASCO provided better developmental outcomes than formulas not containing the supplement.

A study sponsored by March of Dimes and National Institutes of Health suggests that women who take DHA supplements during pregnancy give their babies some degree of added protection against getting common colds.[49] The babies whose mothers had taken DHA supplements seemed to get over cold symptoms faster when they did get sick.

Current research[edit]

Although most studies demonstrate positive effects of dietary DHA on human health, contrary results exist. For example, one study[50] found that the use of DHA-rich fish oil capsules did not reduce postpartum depression in mothers or improve cognitive and language development in their offspring during early childhood (though this is not a negative effect, merely no effect).

Additional studies confirmed DHA benefits for other nervous system functions, cardiovascular health, and potentially other organs. In one study, men who took DHA supplements for 6–12 weeks decreased the concentrations of several inflammatory markers in their blood by approximately 20%.[51] Higher intakes of DHA and EPA may reduce the risk of cardiovascular diseases.[52] A new study found that higher intake of DHA was associated with slower rates of telomere shortening, which is a basic DNA-level marker of aging.[53] Preliminary studies showed that a high intake of DHA was associated with reduced risk for developing Alzheimer's disease[54] and Parkinson's disease[55] consistent with DHA being the most abundant omega-3 fatty acid in the brain. Neuroprotective effects of dietary DHA have been described in animals models of Parkinson's disease.[56] It is now considered so important to brain and eye development that DHA is included in most infant formulas.[57] Lastly, in preliminary research, it was found that a diet rich in DHA might protect stroke victims from brain damage and disability and aid in a speedier recovery.[58] Accordingly, dietary administrered DHA reduces stroke-induced neuroinflammation in animal models.[59]
According to a new study, DHA is very likely important in the formation of the acrosome, an arc-like structure on the top of sperm, which is critical in fertilization because it houses a variety of enzymes that sperm use to penetrate an egg.[60] Because humans and other mammals are able to make their own DHA from other fatty acids, DHA deficiency is not common. But, if that DHA-synthesizing enzyme is defective, it could lead to problems with infertility.[61]

Researchers in Norway are testing a treatment for psoriasis with a synthesised molecule based on DHA.[62]

Nutrition[edit]

Ordinary types of cooked salmon contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams.[63] Additional top fish sources of DHA include tuna, bluefish, mackerel, swordfish, anchovies, herring, sardines, and caviar.

Diets that consist of high doses of omega-3 fatty acids help prevent strokes. There are fewer strokes in countries where people consume high amounts of omega-3 fatty acids, such as Japan and Sweden.[citation needed]

Discovery of algae-based DHA[edit]

In the early 1980s, NASA sponsored scientific research in search of a plant-based food source that could generate oxygen and nutrition on long-duration space flights. The researchers discovered that certain species of marine algae produced rich nutrients. This research led to the development of an algae-based, vegetable-like oil that contains two essential polyunsaturated fatty acids, DHA and ARA (arachidonic acid),[64] which can now be found in health supplements.[65]

Use as a food additive[edit]

DHA is widely used as a food supplement. It was first used primarily in infant formulas.[66] In 2004, the US Food and Drug Administration endorsed qualified health claims for DHA,[67] and by 2007 DHA-fortified dairy items (milk, yogurt, cooking oil) started to appear in grocery stores.

DHA is 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 along with supporting retinal development. Some manufactured DHA is a vegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega-3's such as EPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive.[68]

Studies of vegetarians and vegans[edit]

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 bodies, 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.[69]

DHA and EPA in fish oils[edit]

Fish oil is widely sold in gelatin capsules containing a mixture of omega-3 fatty acids including EPA and smaller quantities of DHA. One study found that fish oil higher in DHA than EPA lowered inflammatory cytokines, such as IL-6 and IL-1β, associated with neurodegenerative and autoimmune diseases. They note the brain normally contains DHA, but not EPA, though both DHA and EPA plasma concentrations increased significantly for participants.[70]

Hypothesized role in human evolution[edit]

An abundance of DHA in seafood has been suggested as being helpful in the development of a large brain,[71] though other researchers claim a terrestrial diet could also have provided the necessary DHA.[72]

See also[edit]

References[edit]

  1. ^ Guesnet P, Alessandri JM; Alessandri (2011). "Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations". Biochimie 93 (1): 7–12. doi:10.1016/j.biochi.2010.05.005. PMID 20478353. 
  2. ^ http://www.websters-online-dictionary.org/definitions/Docosahexaenoic%20Acids
  3. ^ The omega end is the one furthest from the carboxyl group.
  4. ^ a b c Martek Biosciences Corporation (5 April 2007). "History of Martek". Archived from the original on February 5, 2007. Retrieved March 10, 2007. 
  5. ^ a b Burdge, G. C.; Wootton, S. A. (2002). "Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women". British Journal of Nutrition 88 (4): 411–20. doi:10.1079/BJN2002689. PMID 12323090.  edit
  6. ^ a b c Burdge GC, Jones AE, Wootton SA (2002). "Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men". British Journal of Nutrition 88 (4): 355–363. doi:10.1079/BJN2002662. PMID 12323085. 
  7. ^ Malone, J. P. (2011, August). Autistogenesis: A systems theory with evolutionary perspective. Poster presented at the American Psychological Association 119th Annual Convention, Washington, D.C. Abstract retrieved from http://forms.apa.org/convention/viewabstract.cfm?id=110999.
  8. ^ a b Giltay, E.J., Gooren, L. J. G., Toorians, A. W. F. T., Katan, M. B., & Zock, P. L. (2004). Docosahexanoic acid concentrations are higher in women than in men because of estrogenic effects. American Journal of Clinical Nutrition, 80(5), 1167-1174. Retrieved from http://www.ajcn.org/cgi/reprint/80/5/1167
  9. ^ Gary J. Nelson, Darshan S. Kelley. "DHA Lowers Blood Triglycerides in Diet Study". Agricultural Research (USDA). Retrieved September 1998. 
  10. ^ Meharban Singh (March 2005). "Essential Fatty Acids, DHA and the Human Brain from the Indian Journal of Pediatrics, Volume 72" (PDF). Retrieved October 8, 2007. 
  11. ^ Arthur A. Spector (1999). "Essentiality of Fatty Acids from Lipids, Vol. 34". Retrieved October 8, 2007. 
  12. ^ Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. (October 2005). "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. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ McNamara, R. K.; Jandacek, R; Tso, P; Dwivedi, Y; Ren, X; Pandey, G. N. (2013). "Lower docosahexaenoic acid concentrations in the postmortem prefrontal cortex of adult depressed suicide victims compared with controls without cardiovascular disease". Journal of Psychiatric Research 47 (9): 1187–91. doi:10.1016/j.jpsychires.2013.05.007. PMC 3710518. PMID 23759469.  edit
  16. ^ De Caterina, R and Basta, G (June 2001). "n-3 Fatty acids and the inflammatory response – biological background". European Heart Journal Supplements 3 (Supplement D): D42–D49. doi:10.1016/S1520-765X(01)90118-X. 
  17. ^ A Voss, M Reinhart, S Sankarappa and H Sprecher (October 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". The Journal of Biological Chemistry 266 (30): 19995–20000. PMID 1834642. Retrieved January 2, 2011. 
  18. ^ Arsenault, Dany,, Carl Julien et al. (2011). "DHA Improves Cognition and Prevents Dysfunction of Entorhinal Cortex Neurons in 3xTg-AD Mice". PLoS One. 
  19. ^ Calon, Frederic,, Giselle Lim et al. (2004). "Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model". Neuron. 
  20. ^ "DHA Fights Alzheimer’s Brain Plaques in Mice". US Department of Veterans Affairs. 
  21. ^ Lim, Giselle,, Frederic Calon et al. (March 23, 2005). "A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model". The Journal of Neuroscience. 
  22. ^ a b c Quinn JF, Raman R, Thomas RG et al. (November 2010). "Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial". JAMA 304 (17): 1903–11. doi:10.1001/jama.2010.1510. PMC 3259852. PMID 21045096. 
  23. ^ National Institute on Aging (July 16, 2007). "DHA Phase 3 trial in Alzheimer's disease". Retrieved August 10, 2007. 
  24. ^ Calon, Frederic, Greg Cole (2007). "Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: Evidence from animal studies". Prostaglandins Leukot Essent Fatty Acids. 
  25. ^ Joffre, Corinne, A Nadjar et al. (2014). "n-3 LCPUFA improves cognition: the young, the old and the sick". Prostaglandins Leukot Essent Fatty Acids. 
  26. ^ a b Yurko-Mauro, K; McCarthy, D; Rom, D; Nelson, E. B.; Ryan, A. S.; Blackwell, A; Salem Jr, N; Stedman, M; Midas, Investigators (2010). "Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline". Alzheimer's & Dementia 6 (6): 456–64. doi:10.1016/j.jalz.2010.01.013. PMID 20434961.  edit
  27. ^ Matthew, Muldoon; Christopher M. Ryan; Lei Sheu; Jeffrey K. Yao; Sarah M. Conklin; Stephen B. Manuck (January, 28). "Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood". Journal of Nutrition 140 (4): 848–53. doi:10.3945/jn.109.119578. PMC 2838625. PMID 20181791.  Check date values in: |date= (help)
  28. ^ "MIT nutrient mixture improves memory in early Alzheimer’s". CenterWatch News Online. 10 July 2012. Retrieved 14 June 2014. 
  29. ^ Scheltens, P; Twisk, J. W.; Blesa, R; Scarpini, E; von Arnim, C. A.; Bongers, A; Harrison, J; Swinkels, S. H.; Stam, C. J.; De Waal, H; Wurtman, R. J.; Wieggers, R. L.; Vellas, B; Kamphuis, P. J. (2012). "Efficacy of Souvenaid in mild Alzheimer's disease: Results from a randomized, controlled trial". Journal of Alzheimer's disease : JAD 31 (1): 225–36. doi:10.3233/JAD-2012-121189 (inactive 2014-10-11). PMID 22766770.  edit
  30. ^ Yuen, A. W.; Sander, J. W.; Fluegel, D; Patsalos, P. N.; Bell, G. S.; Johnson, T; Koepp, M. J. (2005). "Omega-3 fatty acid supplementation in patients with chronic epilepsy: A randomized trial". Epilepsy & Behavior 7 (2): 253–8. doi:10.1016/j.yebeh.2005.04.014. PMID 16006194.  edit
  31. ^ 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. 
  32. ^ 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. 
  33. ^ Shaikh IAA, Brown I, Schofield AC, Wahle KWJ, Heys SD (November 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. 
  34. ^ Elmesery ME, Algayyar MM, Salem HA, Darweish MM, El-Mowafy AM (April 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. 
  35. ^ Brasky, T. M.; Till, C.; White, E.; Neuhouser, M. L.; Song, X.; Goodman, P.; Thompson, I. M.; King, I. B. et al. (2011). "Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial". American Journal of Epidemiology 173 (12): 1429–39. doi:10.1093/aje/kwr027. PMC 3145396. PMID 21518693. 
  36. ^ Siddiqui et al., Biofactors 37(6): 399-412, 2011: doi:10.1002/biof.181
  37. ^ http://www.fda.gov/food/foodsafety/product-specificinformation/seafood/foodbornepathogenscontaminants/methylmercury/ucm115662.htm
  38. ^ 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. 
  39. ^ http://www.marchofdimes.com/aboutus/49267_55545.asp
  40. ^ 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. 
  41. ^ DHASCO and ARASCO in Infant Formula - Food Standards
  42. ^ Harnam, F; F. Shahidi (May 2004). "Synthesis of structured lipids via acidolysis of docosahexaenoic acid single-cell oil (DHASCO) with capric acid". J Agric Food Chem 52 (10): 2900–2906. doi:10.1021/jf035316f. PMID 15137833. 
  43. ^ Malone, J. P. (2011, April). The systems theory of autistogenesis and its evolutionary implications. Poster presented at the Western Psychological Association 91st Annual Convention, Los Angeles, CA. Convention program retrieved from http://www.westernpsych.org/pdf/WPA%202011%203rd%20Proof.pdf.
  44. ^ Connell, Gary, J. et al. (2001-07-26). "SOLVENTLESS EXTRACTION PROCESS". Retrieved February 8, 2006.  A patent at the WIPO.
  45. ^ Replacing Mother—Imitating Human Breast Milk in the Laboratory. The Cornucopia Institute. January 2008
  46. ^ Developmental Medicine and Child Neurology, March 2000 http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2000.tb00066.x/pdf
  47. ^ http://www.fi.edu/learn/brain/fats.html
  48. ^ Clandinin M, Van Aerde J, Merkel K, Harris C, Springer M, Hansen J, Diersen-Schade D; Van Aerde; Merkel; Harris; Springer; Hansen; Diersen-Schade (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. 
  49. ^ Ramakrishnan, Usha; et al.; Martorell, R.; Parra-Cabrera, S.; Romieu, I.; Ramakrishnan, U. (1 August 2011). "Prenatal Docosahexaenoic Acid Supplementation and Infant Morbidity: Randomized Controlled Trial". Journal of the American Academy of Pediatrics. doi:10.1542/peds.2010-1386. 
  50. ^ Maria Makrides, "The Effects of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children." The Journal of American Medical Association http://jama.ama-assn.org/content/304/15/1675.abstract
  51. ^ Kelley DS et al. DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr. 2009 Mar;139(3):495-501. Epub 2009 Jan 21.
  52. ^ Pauwels, E. K.; Kostkiewicz, M (2008). "Fatty acid facts, Part III: Cardiovascular disease, or, a fish diet is not fishy". Drug news & perspectives 21 (10): 552–61. doi:10.1358/dnp.2008.21.10.1314058 (inactive 2014-03-28). PMID 19221636.  edit
  53. ^ Farzaneh-Far R et al. Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart DiseaseJAMA. 2010;303(3):250-257.
  54. ^ Samieri, C; Lorrain, S; Buaud, B; Vaysse, C; Berr, C; Peuchant, E; Cunnane, S. C.; Barberger-Gateau, P (2013). "Relationship between diet and plasma long-chain n-3 PUFAs in older people: Impact of apolipoprotein E genotype". The Journal of Lipid Research 54 (9): 2559–67. doi:10.1194/jlr.P036475. PMC 3735952. PMID 23801662.  edit
  55. ^ Bazan, N. G.; Molina, M. F.; Gordon, W. C. (2011). "Docosahexaenoic acid signalolipidomics in nutrition: Significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases". Annual Review of Nutrition 31: 321–51. doi:10.1146/annurev.nutr.012809.104635. PMC 3406932. PMID 21756134.  edit
  56. ^ Bousquet, M; Saint-Pierre, M; Julien, C; Salem Jr, N; Cicchetti, F; Calon, F (2008). "Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease". The FASEB Journal 22 (4): 1213–25. doi:10.1096/fj.07-9677com. PMID 18032633.  edit
  57. ^ Aline Hittle. "DHA in Slowing the Progression of AD." Baylor College of Medicine. http://www.bcm.edu/neurology/alzheimers/index.cfm?pmid=16413
  58. ^ "Kathleen Blanchard. "DHA in Fish Oil Could Protect from Stroke Disability." Louisiana State University.
  59. ^ Lalancette-Hébert, M; Julien, C; Cordeau, P; Bohacek, I; Weng, Y. C.; Calon, F; Kriz, J (2011). "Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune response and development of postischemic neuronal damage". Stroke 42 (10): 2903–9. doi:10.1161/STROKEAHA.111.620856. PMID 21852616.  edit
  60. ^ University of Illinois College of Agricultural, Consumer and Environmental Sciences (2012, January 18). Dietary DHA linked to male fertility
  61. ^ Welsh J (2012). "Omega-3s vital for sperm health". LiveScience. Retrieved 27 March 2014. 
  62. ^ Jakobsen SE, Lie E (2013). "New treatment for psoriasis". ScienceNordic. 
  63. ^ "Appendix G2: Original Food Guide Pyramid Patterns and Description of USDA Analyses". Health.gov. Retrieved 15 September 2013. 
  64. ^ Jones, John. "Nutritional Products from Space Research". May 1st, 2001. NASA. 
  65. ^ "Algae Oil Supplements and How They Help". Oily Oily. Retrieved 15 September 2013. 
  66. ^ "FDA: Why is there interest in adding DHA and ARA to infant formulas?". US Food & Drug Administration. Retrieved July 2002. 
  67. ^ "FDA Announces Qualified Health Claims for Omega-3 Fatty Acids". US Food & Drug Administration. 
  68. ^ Rivlin, Gary (2007-01-14). "Magical or Overrated? A Food Additive in a Swirl". The New York Times. Retrieved 2007-01-15. 
  69. ^ Sanders, Thomas A.B. (August–September 2009). "DHA status of vegetarians". Prostaglandins, Leukotrienes, and Essential Fatty Acids (International Society for the Study of Fatty Acids and Lipids) 81 (2–3): 137–141. doi:10.1016/j.plefa.2009.05.013. ISSN 0952-3278. PMID 19500961. 
  70. ^ Vedin I et al. (1 June 2008). "Effects of docosahexaenoic acid–rich n–3 fatty acid supplementation on cytokine release". Am J Clin Nutr 87 (6): 1616–1622. PMID 18541548. 
  71. ^ Crawford, M et al. (2000). "Evidence for the unique function of docosahexaenoic acid (DHA) during the evolution of the modern hominid brain". Lipids 34 (S1): S39–S47. doi:10.1007/BF02562227. PMID 10419087. 
  72. ^ Carlson BA, Kingston JD; Kingston (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. 

External links[edit]