Publication on sialic acid

The role of sialic acid in infant nutrition has been studied by researchers due to its potential supportive roles in brain development and function, resistance to pathogens, gut maturation and immune function.1,2

Publication on sialic acidWhat is sialic acid?
Sialic acid is a naturally occurring breast milk carbohydrate. It is also present in body fluids such as saliva and urine.3 Sialic acid exists in humans as N-acetylneuraminic acid (Neu5Ac), a 9-carbon carbohydrate.3

Early milk or human colostrum contains higher amounts of sialic acid compared with mature milk.4,5 In human milk, sialic acid is mainly bound to human milk oligosaccharides­­ ̶ e.g. sialyllactose ̶ or found in complex brain lipids called gangliosides.6-8 The various sialic components play a role in the development of the intestinal cell walls, as substrate for the gut microflora and, in the infants’ neurological development.7,9,10

Potential benefits of sialic acid

Effects on cognitive development

The highest amount of sialic acid in the body is found in the brain’s grey matter, where it is present in gangliosides and glycoproteins.1 Sialic acids are highly concentrated in the synaptosomal fraction and may play a role in communication between nerve cells and enhance cognitive function.3,11,12

Brain growth and maturation are associated with an increase in gangliosides and sialoproteins. Learning and memory formation are associated with brain glycoproteins and sialoproteins. Advancing age and congenital retardation syndromes are associated with a decrease in gangliosides and sialoproteins in the brain.3,7,10 Dietary gangliosides may be beneficial to neonatal cognitive development, especially for premature and infants with neurologic damage at birth.2

  • Higher brain ganglioside and glycoprotein sialic acid concentrations in breast-fed infants compared to formula-fed infants suggest differences in neurodevelopment.13
  • Sialic acid-containing glycosphingolipids constitute a major component of neuronal cells and are thought to be essential for brain function.14
  • Preclinical studies suggest that early sialic acid supplementation may improve both memory and cognitive performance.3,13,15

Effects on gut and respiratory health

In vitro studies suggest sialic acid may serve as an inhibitor of pathogenic microorganisms, preventing them from attacking cell layers of the gastrointestinal, urogenital and respiratory tract.1,11,16 Additionally, in vitro studies show:

  • Sialylated oligosaccharides in human milk may act as highly specific receptors.3,11
  • Sialyl oligosaccharides may bind enterotoxinogenic (e.g. children and traveler diarrhea) and uropathogenic E. coli species.6,9,11,16,17
  • Sialylated compounds may have growth-promoting effects on bifidobacteria and lactobacilli, both of which are predominantly present in the intestinal microflora of infants fed breast milk.7,9,10
  • Sialylated oligosaccharides may promote intestinal maturation in early life via modulation of the epidermal growth factor (EGF) receptor activation and enhanced adhesion of maternal IgG to infant intestinal epithelium.1
  • Sialylated compounds may reduce risk of respiratory tract infections by altering mucin composition and increasing pathogen phagocytosis.1

Effects on immune function and inflammation

Limited evidence shows that sialic acid and sialylated compounds may play a role in immunomodulation or has an effect on the immune system. For instance, sialic acid may reduce necrotizing enterocolitis in preterm infants and paediatric inflammatory bowel disease. More studies are needed to explore the mechanism, and below are some working hypotheses1:

  • Stimulate endocytosis by dendritic cells.18,19
  • Induce immune regulation by sialic acid-receptors on immune cells.20
  • Induce T-cell skewing, which may lead to suppressed allergy manifestations.21

Key points

  • Breast milk is the best food for babies. Breast milk plays a key role in optimal development of newborns and sialic acids are suggested as one of the components responsible for the many benefits of breast milk.11
  • Dietary sialic acid supplementation has been shown to improve cognitive function in preclinical studies.2,15 Higher brain ganglioside and glycoprotein sialic acid concentrations in breast-fed infants compared to formula-fed infants suggest differences in neurodevelopment.13 More research is needed to confirm whether sialic acid can also contribute to brain function in infants.
  • Sialylated compounds have been shown to inhibit pathogen adhesion to host cells, suggesting they may play a role in protection against infections11 and improving gut microbiota via growth-promoting effects on bifidobacteria and lactobacilli.7,9,10
  • They may also play a role in immunomodulation and inflammation1, and more research is needed to better understand the mechanism.

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References:

  1. ten Bruggencate SJ, et al. Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides. Nutr Rev 2014;72(6):377-89
  2. Ryan JM, et al. The role of gangliosides in brain development and the potential benefits of perinatal supplementation. Nutr Res 2013;33(11):877-87
  3. Wang B, Brand-Miller The role and potential of sialic acid in human nutrition. Eur J Clin Nutr 2003;57:1351-6
  4. McJarrow P, et al. Influence of dietary gangliosides on neonatal brain development. Nutr Rev2009;67(8):451-63
  5. EFSA NDA Panel. Scientific Opinion on the safety of synthetic N-acetyl-D-neuraminic acid as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal 2017;15(7):4918, 28 pp
  6. Martin-Sosa S, et al. Sialyloligosaccharides in human and bovine milk and in infant formulas: variations with the progression of lactation. J Dairy Sci 2003;86(1):52-9
  7. Miller JB, McVeagh P. Human milk oligosaccharides: 130 reasons to breast-fed. Brit J Nutr 1999;82:333-5
  8. Martin-Sosa S, et al. Distribution of sialic acids in the milk of Spanish mothers of full term infants during lactation. Pediatr Gastroenterol Nutr 2004;39(5):499-503
  9. Nakano T, et al. Sialic acid composition in human milk: composition and Acta Paediatr Taiwan 2001;42(1):11-7
  10. McVeagh P, Miller Human milk oligosaccharides: only the breast. J Paediatr Child Health 1997;33:281-6
  11. Lis-Kuberka J, Orczyk-Pawiłowicz M. Sialylated oligosaccharides and glycoconjugates of human milk. The Impact on infant and newborn protection, development and well-being. Nutrients 2019;11(2). pii: E306
  12. Oliveros E, et al. Sialic acid and sialylated oligosaccharide supplementation during lactation improves learning and memory in rats. Nutrients 2018;10(10). pii: E1519
  13. Wang B, et al. Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants. Am J Clin Nutr 2003;78:1024-9
  14. Jenneman R, et al. Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth. Proc Natl Acad Sci USA 2005;102(35):12459-64
  15. Wang B. Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Adv Nutr 2012;3(3):465S-72S
  16. Martin-Sosa S, et al. The sialyated fraction of milk oligosaccharides is partially responsible for binding to enterotoxigenic and uropathogenic Escherichia coli human J Nutr 2002;132:3067-72
  17. Dugan AS, et al. An N-linked glycoprotein with α(2,3)-linked sialic acid is a receptor for BK virus. J Virol 2005;79(22):14442-5
  18. Videira PA, et al. Surface α2-3- and α2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj J 2008;25:259-68
  19. Cabral MG, et al. The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6-sialic acid deficiency. Immunology 2013;138:235-45
  20. Pillai S, et al. Siglecs and immune regulation. Annu Rev Immunol 2012;30:357-92
  21. Eiwegger T, et al. Prebiotic oligosaccharides: in vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatr Allergy Immunol 2010;21:1179-88

 

Important note:

Breastfeeding is the best nutrition for healthy growth and development of babies. Exclusive breastfeeding for six months is the optimal way of feeding infants. Thereafter infants should receive complementary foods with continued breastfeeding up to two years or beyond. Mothers should receive guidance on proper maternal nutrition in order to help sustain an adequate supply and quality of breast milk. Unnecessary introduction of bottle-feeding, partially or fully, or of other complementary foods and drinks may have a negative impact on breastfeeding, which may be irreversible. Mothers should consult their doctor and consider the social and financial implications before deciding to use breast milk substitutes or if they have difficulty breastfeeding. Usage, preparation and storage instructions of breast milk substitutes or of other complementary foods and drinks should be followed carefully as improper or unnecessary use may pose a health hazard.