Advertisement

Polyunsaturated Fatty Acids in Human Milk

An Essential Role in Infant Development
  • Sheila M. Innis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 554)

Abstract

The n-6 and n-3 fatty acids are essential dietary nutrients required for optimal growth and development, particularly of the brain and retina. Large amounts of the n-3 fatty acid docosahexaenoic acid (DHA) is accumulated in the brain grey matter and the visual elements of the retina during development, and reduced DHA in these tissues can result in decreased visual and psychomotor development. Although the possible importance of differences in n-6 and n-3 fatty acids, particularly DHA, between human milk and infant formulas has been the subject of intense clinical research, the variability in the essential fatty acid content of milk within and among different populations of women and implications of this to infant growth and development have received much less attention. Considerable research has shown that the DHA content of the maternal diet is the most important determinant of the amount of DHA secreted in milk, and thus the dietary intake of the breastfed infant. The DHA content of human milk varies over 10-fold, being lowest in women with no intake of DHA and highest in women with high intakes of DHA, which is found predominantly in fatty fish. The requirement for n-3 fatty acids, and the balance of n-6 and n-3 fatty acids for optimal growth and development of the brain and retina, and long-term minimization of risk of chronic disease remains as one of the most important questions in infant nutrition. Dietary reconunendations to modifying dietary fat with the aim of reducing risk of chronic disease, including obesity and cardiovascular disease in adults, need to consider that when followed by pregnant women, these recommendations can have a marked effect on the amount and balance of n-6 and n-3 fatty acids secreted in milk.

Keywords

Polyunsaturated Fatty Acid Human Milk Docosahexaenoic Acid Alpha Linolenic Acid Breastfed Infant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antal A, Keri S, Bodis-Wollner J. Dopamine D2 receptor blockade alters the primary and cognitive components of visual evoked potentials in the monkey, Macaca fasciliaris. Neurosci Lett 1997;232:179–181.PubMedCrossRefGoogle Scholar
  2. Auestad N, Montalto MB, Hall RT, Fitzgerald KM, Wheeler RE, Connor WE, Neuringer M, Connor SE, Hartmann EE. Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Pediatr Res 1997;41:1–10.PubMedCrossRefGoogle Scholar
  3. Auestad N, Halter R, Hall RT, Blatter M, Bogle ML, Burks W, Erickson JR, Fitzgerald KM, Dobson V, Innis SM, Singer LT, Montalto MB, Jacobs JR, Qui W, Bornstein MH. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-blind, randomized, parallel, prospective, multivariate study. Pedaitrics 2001;108:372–381.CrossRefGoogle Scholar
  4. Basmak H, Yildirim N, Erdinc O, Ywdakul S, Ozdemir G. Effect of leuodopa therapy on visual evoked potentials and visual acuity in amblyopia. Ophthalmologica 1999;213:110–113.PubMedCrossRefGoogle Scholar
  5. Calder PC. Polyunsaturated fatty acids, inflammation, and immunity. Lipids 2001;36: 1007–1024.PubMedCrossRefGoogle Scholar
  6. Carlson SE, Cooke RJ, Werkman SH, Tolley EA. First year growth of preterm infants fed standard compared to marine-oil n-3 supplemented formula. Lipids 1992;27:901–907.PubMedCrossRefGoogle Scholar
  7. Carlson SE, Werkman SH, Rhodes PG, Tolley EA. Visual-acuity development in healthy preterm infants, effect of marine-oil supplementation. Am J Clin Nutr 1993a;58:35–42.Google Scholar
  8. Carlson SE, Werkman SH, Peeples JM, Cooke RJ, Tolley EA. Arachidonic acid status correlates with first year growth in preterm infants. Proc Natl Acad Sci USA 1993b;90:1073–1077.CrossRefGoogle Scholar
  9. Carnielli VP, Wattimena DJ, Luijendijk IH, Boerlage A, Degenhost HJ, Sauer PJ. The very low birthweight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linolenic and linolenic acids. Pediatr Res 1996;40:169–174.PubMedCrossRefGoogle Scholar
  10. Chen Z-Y, Pelletier G, Hollywood R, Ratnayake WMN. Trans fatty acid isomers in Canadian human milk . Lipids 1995;30:15–21.PubMedCrossRefGoogle Scholar
  11. Chow C, editor. Fatty Acids in Foods and Their Health Implications. 2nd Edition. New York: Marcel Dekker, 2000.Google Scholar
  12. Chulei R, Xiafang I, Hongseng M Xiulan M, Guizheng I, Gianhong D, DeFrancesco CA, Connor WE. Milk composition in women from five different regions of the China, the great diversity of milk fatty acids. J Nutr 1995;125:2993–2998.Google Scholar
  13. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription, a molecular mechanism to improve metabolic syndrome. J Nutr 2001; 141:1129–1132.Google Scholar
  14. Cunnane SC. New developments in alpha-linolenate metabolism with emphasis on the importance of beta-oxidation and carbon recycling. World Rev Nutr Diet 2001;88:178–183.PubMedCrossRefGoogle Scholar
  15. de la Presa Owens S, Innis SM. Docosahexaenoic and arachidonic acid reverse changes in dopaminergic and sertoninergic neurotransmitters in piglets frontal cortex caused by a linoleic and alpha linolenic acid deficient diet. J Nutr 1999;129:2088–2093.PubMedGoogle Scholar
  16. de la Presa Owens S, Innis SM. Diverse, region specific effects of addition of arachidonic and docosahexaenoic acid to formula with low or adequate linoleic and alpha linolenic acid on piglet brain monoaminergic neurotransmitters. Pediatr Res 2000; 48:125–130.PubMedCrossRefGoogle Scholar
  17. DeLany JP, Windhauser MM, Champagne CM, Bray GA. Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr 2000;72:905–911.PubMedGoogle Scholar
  18. Delion S, Chalon S, Herault J, Guilloteau D, Besnard JC, Durand G. Chronic dietary α-linoleic acid deficiency alters dopaminergic and serotinergic neurotransmitters in rats. J Nutr 1994;124:2466–2476.PubMedGoogle Scholar
  19. Demmelmair H, Schenck UV, Behrendt E, Sauerwalk T, Koletzko B. Estimation of arachidonic acid synthesis in full term neonates using natural variation of 13 C content. J Pediatr Gastroenterol Nutr 1995;21:31–36.PubMedCrossRefGoogle Scholar
  20. Ferdinandusse S, Denis S, Mooijer PAW, Zhang Z, Reddy JK, Spector AA, Wanders RJA. Identification of the peroxisomal β-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid. J Lipid Res 2001;42:1987–1995.PubMedGoogle Scholar
  21. Fidler N, Sauerwald T, Pohl A, Demmelmair H, Koletzko B. Docosahexaenoic acid transfer into human milk after dietary supplementation: a randomized clinical trial. J Lipid Res 2000;41:1376–1383.PubMedGoogle Scholar
  22. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995; 83:803–812.PubMedCrossRefGoogle Scholar
  23. Gava VK, McKean CM. Role of 5-hydroxytryptamine in the modulation of acoustic brainstem (far-field) potentials. Neuropharmacol 1997;16:447–449.Google Scholar
  24. Gibson RA, Neuman MA, Makrides M. Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants. Eur J Clin Nutr 1997;51:578–584.PubMedCrossRefGoogle Scholar
  25. Giusto NM, Pasquare SJ, Salvador GA, Castagnet PI, Roque ME, Ilincheta de Boschero MG. Lipid metabolism in vertebrate retinal rod outer segments. Prog Lipid Res 2000;39:315–391.PubMedCrossRefGoogle Scholar
  26. Gray-Donald K, Jacobs-Starkey L, Johnson-Down L. Food habits of Canadians: reduction in fat intake over a generation. Can J Public Health 2000;91:381–385.PubMedGoogle Scholar
  27. Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiol Rev 1998;78:783–809.PubMedGoogle Scholar
  28. Harris WS, Connor WE, Lindsay S. Will dietary omega -3 fatty acids change the composition of human milk? Am J Clin Nutr 1984;40:780–785.PubMedGoogle Scholar
  29. Heiland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, Drevon CA. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001; 108 :E82–E91.CrossRefGoogle Scholar
  30. Henderson RA, Jenson RG, Lammi-Keefe CJ, Ferris AM, Dardick KR. Effect of fish oil on the fatty acid composition of human milk and maternal and infant erythrocytes. Lipids 1992;27:863–869.PubMedCrossRefGoogle Scholar
  31. Hibbeln JR, Umhau JC, Gorge DT, Salem N Jr. Do plasma polyunsaturates predict hotility and depression? World Rev Nutr Diet 1997;82:175–186.PubMedCrossRefGoogle Scholar
  32. Innis SM. Essential fatty acids in growth and development. Prog Lipid Res 1991;30:39–103.PubMedCrossRefGoogle Scholar
  33. Innis SM. Human milk and formula fatty acids. J Pediatr 1992;120:S56–S61.PubMedCrossRefGoogle Scholar
  34. Innis S.M. Present Knowledge in Nutrition: Essential Dietary Lipids. Pub Int Life Sci Inst, 1996. Chapter 7, pp 58–66.Google Scholar
  35. Innis SM. Perinatal biochemistry and physiology of long chain polyunsaturated fatty acids. J Pediatr 2003a;143(4Suppl):S1–S8.Google Scholar
  36. Innis SM. Essential fatty acid metabolism during early development. In: Biology of Metabolism in Growing Animals. Burrin DG, editor. Amsterdam: Elsevier Science B.V., 2003b.Google Scholar
  37. Innis SM, Kuhnlein HV. Long chain n-3 fatty acids in breast milk of Inuit consuming traditional foods. Early Hum Dev 1988;18:185–189.PubMedCrossRefGoogle Scholar
  38. Innis SM, King DJ. Trans fatty acids in human milk are inversely associated with levels of essential all-cis n-6 and n-3 fatty acids, and determine trans, but not n-6 and n-3 fatty acids in plasma of breast-fed infants. Am J Clin Nutr 1999;70:383–390.PubMedGoogle Scholar
  39. Innis SM, Auestad N, Siegman JS. Blood lipid docosahexaenoic and arachidonic acid in term gestation infants fed formulas with high docosahexaenoic acid, low eicosapentaenoic acid fish oil. Lipids 1996;31:617–25.PubMedCrossRefGoogle Scholar
  40. Innis SM, Gilley J, Werker J. Are human-milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed infants? J Pediatr 2001;139:532–538.PubMedCrossRefGoogle Scholar
  41. Innis SM, Adamkim DH, Hall RT, Kalhan SC, Lair C, Lim M, Stevens DC, Twist PF, Diersen-Schade DA, Harris CL, Merkel KL, Hansen JW. Docosahexaenoic acid and arachidonic acid from single cell triglycerides enhance growth with no adverse effects in preterm infants fed formula. J Pediatr 2002;140:547–554.PubMedCrossRefGoogle Scholar
  42. Innis SM, Elias SL. Essential n-6 and n-3 polyunsaturated fat intakes among Canadian pregnant women. Am J Clin Nutr 2003;77:473–478.PubMedGoogle Scholar
  43. Insull W, Hirsch J, James J, Ahrens EH. The fatty acids of human milk. II. Alterations produced by manipluation of calorie balance and exchange of dietary fats. J Clin Invest 1959;38:443–450.PubMedCrossRefGoogle Scholar
  44. [IOM/NAS]
    Institute of Medicine of the National Academies. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. Washington, DC: The National Academies Press, 2002.Google Scholar
  45. Jensen KG. Lipids in human milk. Lipids 1999;34:1243–1271.PubMedCrossRefGoogle Scholar
  46. 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.PubMedGoogle Scholar
  47. Jorgensen MH, Hernell O, Hughes EL, Michaelsen KF. Is there a relation between docosahexaenoic acid concentration in mothers’ milk and visual development in term infants? J Pediatr Gastroenterol Nutr 2001;32:293–296.PubMedCrossRefGoogle Scholar
  48. Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 2002; 11:8755–9858.CrossRefGoogle Scholar
  49. Kitajka K, Puskas LG, Zvara A, Hackler L Jr, Barcelo-Coblijn G, Yeo YK, Farkas T. The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Nat Acad Sci USA 2002;99:2619–2624.PubMedCrossRefGoogle Scholar
  50. Kneebone GM, Kneebone R, Gibson RA. Fatty acid composition of breast milk from three racial groups from Penang, Malaysia. Am J Clin Nutr 1985;41;765–769.PubMedGoogle Scholar
  51. Koletzko B, Braun M. Arachidonic acid and early human growth, is there a relation? Ann Nutr Metab 1991;35:128–131.PubMedCrossRefGoogle Scholar
  52. Koletzko B, Thiel I, Abiodun PO. The fatty acid composition of human milk in Eurpoe and Africa. J Pediatr 1992;120:S62–S70.PubMedCrossRefGoogle Scholar
  53. Kris-Etherton PM, Taylor DS, Yu-Poh S, Huth P, Monarty K, Fishell V, Hargrove RL, Zhao G, Etherton TD. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 2000;71:179S–188S.PubMedGoogle Scholar
  54. Le Moal M, Simon H. Mesocorticolimbic dopaminergic networks. Physiol Rev 1991;71:155–234.PubMedGoogle Scholar
  55. Litman BJ, Niu SL, Polozova A, Mitchell DC. The role of docosahexaenoic acid containing phospholipids in modulating G protein-coupled signaling pathways: visual transduction. J Mol Neurosci 2001;16:237–242.PubMedCrossRefGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. Makrides M, Neumann MA, Simmer K, Gibson RA. Erythrocyte fatty acids of term infants fed either breast milk, standard formula, or formula supplemented with long-chain polyunsaturates. Lipids 1995b;30:941–948.CrossRefGoogle Scholar
  58. Makrides M, Simmer K, Neuman M, Gibson R. Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation. Am J Clin Nutr 1995a;51:1231–1233.Google Scholar
  59. Makrides M, Neumann MA, Gibson RA. Effect of maternal docosahexaenoic acid (DHA) supplementation on breast milk composition. Eur J Clin Nutr 1996;50:352–357.PubMedGoogle Scholar
  60. Martinez, M. Tissue levels of polyunsaturated fatty acids in early human development. J Pediatr 1992; 120:129–138.CrossRefGoogle Scholar
  61. Mata de Urquiza A, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlman T. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000;290:2140–2144.CrossRefGoogle Scholar
  62. Nakajima H. Comparison of the fatty acid compositon of total lipids and phospholipids in breast milk from Japanese women. Pediatr Int 2000;42:14–20.PubMedCrossRefGoogle Scholar
  63. Ntambi JM, Buhrow SA, Kaestner KH, Christy RJ, Sibley E, Kelley TJ, Lane MD. Differentiation and induced gene expression in 3T3–L1 preadipocytes: characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem 1988;263:17291–17300.PubMedGoogle Scholar
  64. O’Connor DL, Auestad N, Jacobs J. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids, a prospective randomized controlled trial. Pediatrics 2001;108:359–372.PubMedCrossRefGoogle Scholar
  65. Okolo SN, VanderJagt TJ, Vu T, VanderJagt TA, VanderJagt DJ, Okonji M, Chuang L-T, Onwuanaku C, Glew RH. The fatty acid composition of human milk in Northern Nigeria. J Hum Lact 2000;16:28–35.PubMedCrossRefGoogle Scholar
  66. Okuno M, Kajiwara K, Imai S, Kobayashi T, Honma N, Maki T, Suruga K, Goda T, Takase S, Muto Y, Moriwaki H. Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation. J Nutr 1997;127:1752–1757.PubMedGoogle Scholar
  67. Ponder DL, Innis SM, Benson JD, Siegman JS. Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil. Pediatr Res 1992;32:683–688.PubMedCrossRefGoogle Scholar
  68. Putnam JC, Carlson SE, DeVoe PW, Barness LA. The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am J Clin Nutr 1982;36:106–114.PubMedGoogle Scholar
  69. Reginato MJ, Krakow SL, Bailey ST, Lazar MA. Prostaglandins promote and block adipogenesis through opposing effects on peroxisome proliferator-activated receptor gamma. J Biol Chem 1998;273:1855–1858.PubMedCrossRefGoogle Scholar
  70. Salem N Jr, Wegher B, Mena P, Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci USA 1996;93:49–54.PubMedCrossRefGoogle Scholar
  71. Sanders TAB, Reddy S. The influence of vegetarian diet on the fatty acid composition of human milk and essential fatty acid status of the infant. J Pediatr 1992;120:71S–77S.CrossRefGoogle Scholar
  72. SanGiovanni JP, Parra-Cabrera S, Colditz GA, Berkey CS, Dwyer JT. Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. Pediatrics 2000;105:1292–1298.PubMedCrossRefGoogle Scholar
  73. Sastry PS. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 1985;24:169–176.CrossRefGoogle Scholar
  74. Sauerwald TU, Hachey DL, Luijendijik IHT, Boerlage A, Degerhart HJ, Sauer PJJ. New insights into the metabolism of long chain polyunsaturated fatty acids during infancy. Eur J Med Res 1996;2:88–92.Google Scholar
  75. Schmeits BL, Okolo SN, VanderJagt DJ, Huang Y-S, Chuang L-T, Mata JR, Tsin AATC, Glew RH. Content of lipid nutrients in the milk of Fulani women. J Human Lact 1999; 15:113–120.CrossRefGoogle Scholar
  76. Simopoulos AP. Evolutionary aspects of omega-3 fatty acids in the food supply. Prostaglandins Leukot Essent Fatty Acids 1999;60:421 – 429.PubMedCrossRefGoogle Scholar
  77. Smit EN, Koopmann M, Boersma ER, Muskiet FAJ. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosaehxaenoic acid on breastmilk fatty acid composition. Prostaglandins Leukot Essent Fatty Acids 2000;62:335–340.PubMedCrossRefGoogle Scholar
  78. Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP. Réévaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 1995;36:2471–2477.PubMedGoogle Scholar
  79. Sprecher H, Chen Q, Yin FQ. Regulation of the biosynthesis of 22:5n-6 and 22:6n-3: a complex intracellular process. Lipids 1999;34:S153–S156.PubMedCrossRefGoogle Scholar
  80. Tomarelli RM, Myer BJ, Weaber JR, Bernhart FW. Effect of positional distribution on the absorption of the fatty acids of human milk and infant formulas. J Nutr 1968;95:583–590.PubMedGoogle Scholar
  81. Toschke AM, Vignerova J, Lhotska L, Oscancova K, Koletzko B, von Kries R. Overweight and obesity in 6- to 14- year old Czech children in 1991 : protective effect of breastfeeding. J Pediatr 2002;141:764–769.PubMedCrossRefGoogle Scholar
  82. Uauy R, Mena P, Wegher B, Nieto S, Salem N Jr. Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res 2000;47:127–135.PubMedCrossRefGoogle Scholar
  83. Von Kries R, Koletzko B, Sauerwald T, Von Mutius E, Barnert D, Grunet V, von Voss H. Breast feeding and obesity: cross-sectional study. Br Med J 1999;319:147–150.CrossRefGoogle Scholar
  84. Ximenes da Sliva A, Lavialle F, Gendrot G, Guesnet P, Alessandri JM, Lavaille M. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem 2002;81:1328–1337.CrossRefGoogle Scholar
  85. Zimmer L, Vancassel S, Contagrel S, Breton P, Delmanche S, Guilloteau D, Durand G. The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr 2002;75:662–777.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Sheila M. Innis
    • 1
  1. 1.Department of Paediatrics, B.C. Research Institute for Children’s and Women’s HealthUniversity of British ColumbiaVancouverCanada

Personalised recommendations