Abstract
Docosahexaenoic acid (DHA) is a long-chain, highly unsaturated omega-3 (n-3) fatty acid. It has a structure that gives it unique physical and functional properties. DHA is metabolically related to other n-3 fatty acids: it can be synthesised from the plant essential fatty acid α-linolenic acid (ALA). However, this pathway does not appear to be very efficient in many individuals, although the conversion of ALA to DHA is much better in young women than in young men. Furthermore, young infants may be more efficient converters of ALA to DHA than many adults, although the conversion rate is variable among infants. Many factors have been identified that affect the rate of conversion. The implication of poor conversion is that preformed DHA needs to be consumed. DHA is found in fairly high amounts in seafood, especially fatty fish, and in various forms of n-3 supplements. The amount of DHA in seafood and in supplements varies. Breast milk contains DHA. DHA is found esterified into complex lipids within the bloodstream, in adipose stores and in cell membranes. Its concentration in different compartments varies greatly. The brain and eye have high DHA contents compared to other organs. DHA is especially concentrated in the grey matter of the brain and in the rod outer segments of the retina. In the brain DHA is involved in neuronal signalling, while in the eye it is involved in the quality of vision. DHA is accumulated in the brain and eye late in pregnancy and in early infancy. A lower DHA content is linked to poorer cognitive development and visual function. DHA affects cell and tissue physiology and function through numerous mechanisms, including alterations in membrane structure and function, in membrane protein function, in cellular signalling and in lipid mediator production.
Journal Section:
The Role of DHA in the First 1,000 Days
References
1.
Childs CE, Romeu-Nadal M, Burdge GC, Calder PC: Gender differences in the n-3 fatty acid content of tissues. Proc Nutr Soc 2008;67:19-27.
2.
Lohner S, Fekete K, Marosvolgyi T, Decsi T: Gender differences in the long-chain polyunsaturated fatty acid status: systematic review of 51 publications. Ann Nutr Metab 2013;62:98-112.
3.
Schaeffer L, Gohlke H, Muller M, Heid IM, Palmer LJ, Kompauer I, Demmelmair H, Illig T, Koletzko B, Heinrich J: Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 2006;15:1745-1756.
4.
Burdge GC, Jones AE, Wootton SA: Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men. Br J Nutr 2002;88:355-363.
5.
Burdge GC, Wootton SA: Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 2002;88:411-420.
6.
Carnielli VP, Simonato M, Verlato G, Luijendijk I, De Curtis M, Sauer PJ, Cogo PE: Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids. Am J Clin Nutr 2007;86:1323-1330.
7.
British Nutrition Foundation: n-3 Fatty Acids and Health. London, British Nutrition Foundation, 1999.
8.
Brenna JT, Varamini B, Jensen RG, Diersen-Schade DA, Boettcher JA, Arterburn LM: Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr 2007;85:1457-1464.
9.
Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR: Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids 2003:38;391-398.
10.
Howe P, Meyer B, Record S, Baghurst K: Dietary intake of long-chain omega-311 polyunsaturated fatty acids: contribution of meat sources. Nutrition 2006;22:47-53.
11.
Browning LM, Walker CG, Mander AP, West AL, Madden J, Gambell JM, Young S, Wang L, Jebb SA, Calder PC: Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. Am J Clin Nutr 2012;96:748-758.
12.
Miles EA, Noakes PS, Kremmyda LS, Vlachava M, Diaper ND, Rosenlund G, Urwin H, Yaqoob P, Rossary A, Farges MC, Vasson M-P, Liaset B, Frøyland L, Helmersson J, Basu S, Garcia E, Olza J, Mesa MD, Aguilera CM, Gil A, Robinson SM, Inskip HM, Godfrey KM, Calder PC: The Salmon in Pregnancy Study: study design, subject characteristics, maternal fish and marine n-3 fatty acid intake, and marine n-3 fatty acid status in maternal and umbilical cord blood. Am J Clin Nutr 2011;94:1986S-1992S.
13.
Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P: The effect of low to moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 2000;35:763-768.
14.
Skinner ER, Watt C, Besson JA, Best PV: Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects. Brain 1993;116:717-725.
15.
Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA: Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 1994;60:189-194.
16.
Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, Porter CB, Borkon AM: Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocyes and response to supplementation. Circulation 2004;110:1645-1649.
17.
Metcalf RG, James MJ, Gibson RA, Edwards JR, Stubberfield J, Stuklis R, Roberts-Thomson K, Young GD, Cleland LG: Effects of fish-oil supplementation on myocardial fatty acids in humans. Am J Clin Nutr 2007;85:1222-1228.
18.
McGlory C, Galloway SD, Hamilton DL, McClintock C, Breen L, Dick JR, Bell JG, Tipton KD: Temporal changes in human skeletal muscle and blood lipid composition with fish oil supplementation. Prostaglandins Leukot Essent Fatty Acids 2014;90:199-206.
19.
Smith GI, Atherton P, Reeds DN, et al: Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci 2011;121:267-278.
20.
Araya J, Rodrigo R, Videla LA, Thielemann L, Orellana M, Pettinelli P, Poniachik J: Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin Sci 2004;106:635-643.
21.
Elizondo A, Araya J, Rodrigo R, Poniachik J, Csendes A, Maluenda F, Díaz JC, Signorini C, Sgherri C, Comporti M, Videla LA: Polyunsaturated fatty acid pattern in liver and erythrocyte phospholipids from obese patients. Obesity 2007;15:24-31.
22.
Hillier K, Jewell R, Dorrell L, Smith CL: Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease. Gut 1991;32:1151-1155.
23.
Safarinejad MR: Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study. Andrologia 2011;43:38-47.
24.
O'Brien JS, Sampson EL: Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter, and myelin. J Lipid Res 1965;6:545-551.
25.
Crawford MA, Casperd NM, Sinclair AJ: The long chain metabolites of linoleic avid linolenic acids in liver and brain in herbivores and carnivores. Comp Biochem Physiol B 1976;54:395-401.
26.
Anderson RE: Lipids of ocular tissues. IV. A comparison of the phospholipids from the retina of six mammalian species. Exp Eye Res 1970;10:339-344.
27.
Dobbing J, Sands J: Quantitative growth and development of human brain. Arch Dis Child 1973;48:757-767.
28.
Cunnane SC, Francescutti V, Brenna JT, Crawford MA: Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula-fed infants not consuming dietary docosahexaenoate. Lipids 2000;35:105-111.
29.
Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF: The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001;40:1-94.
30.
Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW: Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. Early Hum Dev 1980;4:121-129.
31.
Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G: Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995;74:55-68.
32.
Otto SJ, Houwelingen AC, Antal M, Manninen A, Godfrey K, Lopez-Jaramillo P, Hornstra G: Maternal and neonatal essential fatty acid status in phospholipids: an international comparative study. Eur J Clin Nutr 1997;51:232-242.
33.
Al MD, van Houwelingen AC, Hornstra G: Relation between birth order and the maternal and neonatal docosahexaenoic acid status. Eur J Clin Nutr 1997;51:548-553.
34.
Haggarty P: Fatty acid supply to the human fetus. Ann Rev Nutr 2010;30:237-255.
35.
Calder PC: Very long chain omega-3 (n-3) fatty acids and human health. Eur J Lipid Sci Technol 2014;116:1280-1300.
36.
Katan MB, Deslypere JP, van Birgelen APJM, Penders M, Zegwaars M: Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes and adipose tissue: an 18 month controlled study. J Lipid Res 1997;38:2012-2022.
37.
Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC: Dietary supplementation with γ-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 2001;131:1918-1927.
38.
Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC: Dietary supplementation with eicosapentaenoic acid, but not with other long chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 years. Am J Clin Nutr 2001;73:539-548.
39.
Olsen SF, Hansen HS, Sommer S, Jensen B, Sorensen TI, Secher NJ, Zachariassen P: Gestational age in relation to marine n-3 fatty acids in maternal erythrocytes: a study of women in the Faroe Islands and Denmark. Am J Obstet Gynecol 1991;164:1203-1209.
40.
Sanjurjo P, Matorras R, Perteagudo L: Influence of fatty fish intake during pregnancy in the polyunsaturated fatty acids of erythrocyte phospholipids in the mother at labor and newborn infant. Acta Obstet Gynecol Scand 1995;74:594-598.
41.
Connor WE, Lowensohn R, Hatcher L: Increased docosahexaenoic acid levels in human newborn infants by administration of sardines and fish oil during pregnancy. Lipids 1996;31:S183-S187.
42.
van Houwelingen AC, Sorensen JD, Hornstra G, Simonis MM, Boris J, Olsen SF, Secher NJ: Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy. Br J Nutr 1995;74:723-731.
43.
Dunstan JA, Mori TA, Barden A, Beilin LJ, Holt PG, Calder PC, Taylor AL, Prescott SL: Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr 2004;58:429-437.
44.
Montgomery C, Speake BK, Cameron A, Sattar N, Weaver LT: Maternal docosahexaenoic acid supplementation and fetal accretion. Brit J Nutr 2003;90:135-145.
45.
Harris WS, Connor WE, Lindsey S: Will dietary omega-3 fatty acids change the composition of human milk? Am J Clin Nutr 1984;40:780-785.
46.
Hawkes JS, Bryan DL, Makrides M, Neumann MA, Gibson RA: A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha. Am J Clin Nutr 2002;75:754-760.
47.
Jensen CL, Maude M, Anderson RE, Heird WC: Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. Am J Clin Nutr 2000;71:292S-299S.
48.
Urwin HJ, Miles EA, Noakes PS, Kremmyda LS, Vlachava M, Diaper ND, Pérez-Cano FJ, Godfrey KM, Calder PC, Yaqoob P: Salmon consumption during pregnancy alters fatty acid composition and secretory IgA concentration in human breast milk. J Nutr 2012;142:1603-1610.
49.
Miles EA, Calder PC: Modulation of immune function by dietary fatty acids. Proc Nutr Soc 1998;57:277-292.
50.
Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LB, Ciappolino V, Agostoni C: DHA effects in brain development and function. Nutrients 2016;8:6.
51.
Cakiner-Egilmez T: Omega 3 fatty acids and the eye. Insight 2008;33:20-25.
52.
Mitchell DC, Litman BJ: Docosahexaenoic acid-containing phospholipids optimally promote rhodopsin activation; in Riemersma RA, Armstrong R, Kelly RW, Wilson R (eds): Essential Fatty Acids and Eicosanoids: Invited Papers from the Fourth International Congress. Champaign, American Oil Chemists' Society, 1998, pp 154-158.
53.
Zapata-Gonzalez F, Rueda F, Petriz J, Domingo P, Villarroya F, Diaz-Delfin J, de Madariaga MA, Domingo JC: Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison with other polyunsaturated fatty acids. J Leukoc Biol 2008;84:1172-1182.
54.
Lefils-Lacourtablaise J, Socorro M, Géloën A, Daira P, Debard C, Loizon E, Guichardant M, Dominguez Z, Vidal H, Lagarde M, Bernoud-Hubac N: The eicosapentaenoic acid metabolite 15-deoxy-δ(12,14)-prostaglandin J3 increases adiponectin secretion by adipocytes partly via a PPARγ-dependent mechanism. PLoS One 2013;8:e63997.
55.
Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ: Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-1015.
56.
Bhaswant M, Poudyal H, Brown L: Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids. J Nutr Biochem 2015;26:571-584.
57.
Calder PC: Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 2015;1851:469-484.
58.
Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM: GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010;142:687-698.
59.
Bannenberg G, Serhan CN: Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim Biophys Acta 2010;1801:1260-1273.
60.
Serhan CN, Yacoubian S, Yang R: Anti-inflammatory and proresolving lipid mediators. Annu Rev Pathol 2008;3:279-312.
61.
Mas E, Croft KD, Zahra P, Barden A, Mori TA: Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. Clin Chem 2012;58:1476-1484.
62.
Titos E, Clària J: Omega-3-derived mediators counteract obesity-induced adipose tissue inflammation. Prostaglandins Other Lipid Mediat 2013;107:77-84.
63.
Weiss GA, Troxler H, Klinke G, Rogler D, Braegger C, Hersberger M: High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation. Lipids Health Dis 2013;12:89.
© 2016 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2016
You do not currently have access to this content.
