Long-Chain Polyunsaturated Fatty Acids in Breast Milk

Are They Essential
  • Robert A. Gibson
  • Maria Makrides
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 501)


The need for long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA, C22:6n3) and arachidonic acid (AA, C20:4n6), in the diet of infants in order to achieve full developmental potential is a matter of intense investigation by several research groups worldwide. It has been widely reported that breast-fed infants perform better on tests that assess neurodevelopmental outcomes than do formula-fed infants. Although human milk contains LC-PUFA that are absent from formula, it is necessary to demonstrate that any beneficial effects of human milk on infant development are purely attributed to the presence of LC-PUFA in human milk and their absence from formula to establish causality. The hypothesis that dietary DHA is associated with developmental outcome needs to be plausible; the effect must be consistent, specific, and independent of confounding factors. The hypothesis is certainly plausible. DHA is avidly incorporated and retained in brain cerebral phospholipids, and a most consistent finding has been the lower level of cerebral DHA in the brains of formula-fed infants (receiving no DHA) relative to those fed human milk (receiving DHA). The formula-fed infants in these studies were generally fed formulas with adequate a-linolenic acid levels, and this may indicate a nutritional requirement for preformed DHA.

Several studies have compared the effects of breast-and formula-feeding on functional outcomes in preterm and term infants. While many of the outcomes have involved visual testing, others have attempted more global assessments. The results have shown differences in favor of breast-feeding but have been colored by the strong socioeconomic differences between mothers who choose to breast feed and those who choose formula-feeding.

Randomized clinical trials involving preterm infants have shown a clear requirement for DHA for full visual and neural development. These results are consistent with primate studies. However, intervention studies with term infants that have attempted to improve the DHA supply of infant formula and hence infant development have not yielded consistent results. Some randomized studies have demonstrated improved visual and developmental indices in supplemented over unsupplemented infants, others have failed to demonstrate an effect. This disparity could be due to methodological and environmental differences. It is also notable that supplemental regimens have not specifically added DHA and have included other LC-PUFA, raising the question as to the specificity of the effect. However, only tissue DHA levels have consistently correlated with outcomes.


Preterm Infant Human Milk Essential Fatty Acid Infant Formula Chain Polyunsaturated Fatty Acid 
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  1. Agostoni C, Trojan S, Bellú R, Riva E, Giovannini M. Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: The role of long-chain polyunsaturated fatty acids. Pediatr Res 1995;38:262–266.PubMedCrossRefGoogle Scholar
  2. Auestad N, Montalto MB, Hall RT, Fitzgerald KM, Wheeler RE, Connor WE, Neuringer M, Connor SL, Taylor JA, 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. Baur LA, O’Conner J, Pan DA, Kriketos AD, Storlien LH. The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with type of feeding and plasma glucose levels in young children. Metabolism 1998;47:1–8.CrossRefGoogle Scholar
  4. Birch DG, Birch EE, Hoffman DR, Uauy RD. Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Invest Ophthalmol Vis Sci 1992a;33:2365–2376.Google Scholar
  5. Birch EE, Birch DG, Hoffman DR, Uauy R. Dietary essential fatty acid supply and visual acuity development. Invest Ophthalmol Vis Sci 1992b;32:3242–3253.Google Scholar
  6. Birch EE, Birch DG, Hoffman DR, Uauy R, Bane MC, Castaneda YS, Wheaton D, Prestidge CB. Visual maturation of term infants fed omega-3 long chain polyunsaturated fatty acid (LC-PUFA) supplemented formula. Invest Ophthalmol Vis Sci 1996;37:S1112.Google Scholar
  7. Brown ME. Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids 1994;73:159–180.PubMedCrossRefGoogle Scholar
  8. Carlson SE, Werkman SH. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months. Lipids 1996;31:85–90.PubMedCrossRefGoogle Scholar
  9. 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
  10. 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
  11. 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
  12. Carlson SE, Werkman SH, Peeples JM, Wilson WM. Growth and development of premature infants in relation to omega 3 and omega 6 fatty acid status. World Rev Nutr Diet 1994;75:63–69.PubMedGoogle Scholar
  13. Carlson SE, Werkman SH, Tolley EA. Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. Am J Clin Nutr 1996;63:687–697.PubMedGoogle Scholar
  14. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor a and interleukin 13 production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 1996;63:116–122.PubMedGoogle Scholar
  15. Caughey GE, Pouliot M, Cleland LG, James MJ. Regulation of tumor necrosis factor-a and IL-1(3 synthesis by thromboxane A2 in nonadherent human monocytes. J Immunol 1997;158:351–358.PubMedGoogle Scholar
  16. Combs GF Jr. Should intakes with beneficial actions, often requiring supplementation, be considered for RDAs? J Nutr 1996;126:23735–23765.Google Scholar
  17. Cuthbertson WFJ. Essential fatty acid requirements in infancy. Am J Clin Nutr 1976;29:559–568.PubMedGoogle Scholar
  18. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989;320:265–271.PubMedCrossRefGoogle Scholar
  19. Faldella G, Govoni M, Alessandroni R, Marchiani E, Salvioli GP, Biagi PL, Spanb C. Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Arch Dis Child Fetal Neonatal 1996;75:F108–F112.CrossRefGoogle Scholar
  20. Gibson R, Neumann M, Makrides M. A randomised clinical trial of long chain polyunsaturated fatty acid supplementation in term infants: effect on neural indices. Inform 1997a;5A.Google Scholar
  21. Gibson RA, Neumann MA, Makrides M. Effect of increasing breast milk docosahexanoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast-fed infants. Eur J Clin Nutr 1997b;51:578–584.CrossRefGoogle Scholar
  22. Holman RT, Johnson SB, Hatch TE A case of human linolenic acid deficiency involving neurological abnormalities. Am J Clin Nutr 1982;35:617–623.PubMedGoogle Scholar
  23. Innis SM. Human milk and formula fatty acids. J Pediatr 1992;120:S56–S61.PubMedCrossRefGoogle Scholar
  24. Jensen RG. The Lipids of Human Milk. Boca Raton FL: CRC Press; 1989. p 213.Google Scholar
  25. Jorgensen MH, Hernell 0, Lund P, Holmer G, Michaelsen KF Visual acuity of 4 months term infants in relation to DHA intake; a randomised study. [Abstract] J Pediatr Gastroenterol Nutr 1996;22:436A.Google Scholar
  26. Koletzko B, Thiel I, Abiodun PO. The fatty acid composition of human milk in Europe and Africa. J Pediatr 1992;120:S62–S70.PubMedCrossRefGoogle Scholar
  27. Lucas A, Brooke OG, Morley R, Cole TJ, Bamford ME. Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. BMJ 1990;300:837–840.PubMedCrossRefGoogle Scholar
  28. Makrides M, Gibson RA. Are long chain polyunsaturated fatty acids essential nutrients in infancy? In: Riemersma RA, editor. Essential Fatty Acids and Eicosanoids. Invited papers from the 46International Congress on Essential Fatty Acids and Eicosanoids. Edinburgh, Scotland; July 20–24, 1997. Champaign IL: AOCS Press; 1998.Google Scholar
  29. Makrides M, Simmer K, Neumann M, Gibson R. Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30wk of lactation. Am J Clin Nutr 1995a;61:1231–1233.Google Scholar
  30. Makrides M, Neumann M, Simmer K, Pater J, Gibson R. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 1995b;345:1463–1468.CrossRefGoogle Scholar
  31. Makrides M, Neumann MA, Gibson RA. Effect of maternal docosahexanoic acid (DHA) supplementation on breast milk composition. Eur J Clin Nutr 1996;50:352–357.PubMedGoogle Scholar
  32. Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 1991;121:547–555.PubMedGoogle Scholar
  33. Mohrhauer H, Holman RT. Effect of linolenic acid upon the metabolism of linoleic acid. J Nutr 1963; 81:67–74.PubMedGoogle Scholar
  34. Neuringer M, Connor WE, Van Petten C, Barstad L. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest 1984;73:272–276.PubMedCrossRefGoogle Scholar
  35. Neuringer M, Connor WE, Lin DS, Barstad L, Luck S. Biochemical and functional effects of prenatal and postnatal omega-3 fatty acid deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci USA 1986;83:4021–4025.Google Scholar
  36. Taylor KB, Anthony LE, editors. Clinical Nutrition. New York: McGraw-Hill; 1983. p 631.Google Scholar
  37. Uauy R, Hoffman DR, Birch EE, Birch DG, Jameson DM, Tyson J. Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: Soy oil and marine oil supplementation of formula. J Pediatr 1994;124:612–620.PubMedCrossRefGoogle Scholar
  38. Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed docosahexanoic acid until nine months. Lipids 1996;31:91–97.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Robert A. Gibson
    • 1
  • Maria Makrides
    • 2
  1. 1.Child Nutrition Research Centre Child Health Research Institute Flinders Medical CentreBedford Park (Adelaide)Australia
  2. 2.Department of Obstetrics and Gynaecology University of AdelaideWomen’s and Children’s Hospital North AdelaideAustralia

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