Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The role and potential of sialic acid in human nutrition

Abstract

Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins. In the human body, the highest concentration of sialic acid (as N-acetylneuraminic acid) occurs in the brain where it participates as an integral part of ganglioside structure in synaptogenesis and neural transmission. Human milk also contains a high concentration of sialic acid attached to the terminal end of free oligosaccharides, but its metabolic fate and biological role are currently unknown. An important question is whether the sialic acid in human milk is a conditional nutrient and confers developmental advantages on breast-fed infants compared to those fed infant formula. In this review, we critically discuss the current state of knowledge of the biology and role of sialic acid in human milk and nervous tissue, and the link between sialic acid, breastfeeding and learning behaviour.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Agnati LF, Fuxe K, Benfenati F, Battistini N, Zini I & Toffano G (1983): Chronic ganglioside treatment counteracts the biochemical signs of dopamine receptor supersensitivity induced by chronic haloperidol treatment. Neurosci. Lett. 40, 293–297.

    Article  CAS  PubMed  Google Scholar 

  • Alvi MH, Amer NA & Sumerin I (1988): Serum 5-nucleotidase and serum sialic acid in pregnancy. Obstet. Gynecol. 72, 171–174.

    CAS  PubMed  Google Scholar 

  • Anderson JW, Johnstone BM & Remley DT (1999): Breast-feeding and cognitive development: a meta-analysis. Am. J. Clin. Nutr. 70(4), 525–535.

    Article  CAS  PubMed  Google Scholar 

  • Annunziata P, Federico A, D'Amore I, Corona RM & Guazzi GC (1983): Impairment of human brain development: glycoconjugate and lipid changes in congenital athyroidism. Early Hum. Dev. 8, 269–278.

    Article  CAS  PubMed  Google Scholar 

  • Atkinson SA & Lonnerdal B (1995): Nonprotein nitrogen fractions of human milk. In Handbook of Milk Composition, ed. RG Jensen, pp 369–385. San Diego: Academic Press.

    Chapter  Google Scholar 

  • Beitinger H, Vogel V, Mobius D & Rahmann H (1989): Surface potentials and electric dipole moments of ganglioside and phospholipid bilayers: contribution of the polar headgroup at the water/lipid interface. Biochim. Biophys. Acta 984, 293–300.

    Article  CAS  PubMed  Google Scholar 

  • Berra B, Lindi C, Omodeo-Sale F, Beltrame D & Cantone A (1981): Effect of maternal diet on ganglioside distribution in fetal rat brain. J. Nutr. 111, 1980–1984.

    Article  CAS  PubMed  Google Scholar 

  • Bogoch S (1970): Glycoproteins of the brain of the training pigeon. In Protein Metabolism of the Nervous System, ed. A Lajtha, pp 535–569. New York: Plenum Press.

    Google Scholar 

  • Bogoch S (1977): Recognins and their chemoreciprocals. In Behavioral Neurochemistry. eds FV DeFeudis & JMR Delgado, p 270. New York:Spectrum Pubs.

    Google Scholar 

  • Brand-Miller JC, McVeagh P, McNeil Y & Messer M (1998): Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test. J. Pediatr. 133, 95–98.

    Article  CAS  PubMed  Google Scholar 

  • Brand Miller JC, Miller JJ, McVeagh P & Bull S (1994): The oligosaccharide composition of human milk: temporal and individual variations in monosaccharides components. J. Pediatr. Gastroenterol. Nutr. 19, 371–376.

    Article  Google Scholar 

  • Briese V, Kunkel S, Plath C, Wutzke KD & Plesse R (1999): Sialic acid, steroids and proteohormones in maternal, cord and retroplacental blood. Z. Geburtshilfe Neonatol. 203, 63–68.

    CAS  PubMed  Google Scholar 

  • Brunngraber EG, Witting LA, Haberland C & Brown B (1972): Glycoproteins in Tay-sachs disease: isolation and carbohydrate composition of glycopeptides. Brain Res. 38, 151–162.

    Article  CAS  PubMed  Google Scholar 

  • Byrne MC, Farooq M, Sbaschnig-Agler M, Norton WT & Ledeen RW (1988): Ganglioside content of astroglia and neurons isolated from maturing rat brain: consideration of the source of astroglial gangliosides. Brain Res. 461, 87–97.

    Article  CAS  PubMed  Google Scholar 

  • Cabezas JA & Calvo P (1984): Gangliosidos. Sci. Am. (Spanish ed) 6, 86–95.

    Google Scholar 

  • Campbell RJ, Bogoch S, Scolaro MJ & Belval PC (1967): Cerebrospinal fluid glycoproteins in schizophrenia. Am. J. Psychiatry 123, 952–962.

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi P, Warren CD, Ruiz-Palacios GM, Pickering LK & Newburg DS (1997): Milk oligosaccharide profiles by reversed-phase HPLC of their perbenzoylated derivatives. Anal. Biochem. 251, 89–97.

    Article  CAS  PubMed  Google Scholar 

  • Carlson SE (1985): N-acetylneuraminic acid concentrations in human milk oligosaccharides and glycoproteins during lactation. Am. J. Clin. Nutr. 41, 720–726.

    Article  CAS  PubMed  Google Scholar 

  • Carlson SE & House SG (1986): Oral and intraperitoneal administration of N-acetylneuraminic acid: effect on rat cerebral and cerebellar N-acetylneuraminic acid. J. Nutr. 116, 881–886.

    Article  CAS  PubMed  Google Scholar 

  • Carlson SE, Werkman SH, Peeples JM & Wilson WM (1994): Long-chain fatty acids and early visual and cognitive development of preterm infants. Eur. J. Clin. Nutr. 48(Suppl 2), S27–S30.

    PubMed  Google Scholar 

  • Carlson SE, Werkman SH & Tolley EA (1996): 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. 63, 687–697.

    Article  CAS  PubMed  Google Scholar 

  • Castillo PE, Weisskopf MG & Nicoll RA (1994): The role of Ca2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation. Neuron 12, 261–269.

    Article  CAS  PubMed  Google Scholar 

  • Chaturvedi P, Warren CD, Ruiz-Palacios GM, Pickering LK & Newburg DS (1997): Milk oligosaccharide profiles by reversed-phase HPLC of their perbenzoylated derivatives. Anal. Biochem. 251, 89–97.

    Article  CAS  PubMed  Google Scholar 

  • Coppa GV, Gabrielli O, Pierani P, Catassi C, Carlucci A & Giorgi PL (1993): Changes in carbohydrate composition in human milk over 4 months of lactation. Pediatrics 91, 637–641.

    Article  CAS  PubMed  Google Scholar 

  • Coppa GV, Pierani P, Zampini L, Carloni I, Carlucci A & Gabrielli O (1999): Oligosaccharides in human milk during different phases of lactation. Acta. Paediatr. 88(Suppl.), 89–94.

    Article  CAS  Google Scholar 

  • Coppa GV, Pierani P, Zampini L, Gabrielli O, Carlucci A, Catassi C et al (1997): Lactose, oligosaccharide and monosaccharide content of milk from mothers delivering preterm newborns over the first month of lactation. Minerva Pediatr. 49, 471–475.

    CAS  PubMed  Google Scholar 

  • Corfield AP, Wagner SA, Safe A, Mountford RA, Clamp JR, Kamerling JP, Vliegenthart JF & Schauer R (1993): Sialic acids in human gastric aspirates: detection of 9-O-lactyl- and 9-O-acetyl-N-acetylneuraminic acids and a decrease in total sialic acid concentration with age. Clin. Sci. (Colch) 84, 573–579.

    Article  CAS  Google Scholar 

  • Corfield AP, Wember M, Schauer R & Rott R (1982): The specificity of viral sialidases. The use of oligosaccharide substrates to probe enzymic characteristics and strain-specific differences. Eur. J. Biochem. 124, 521–525.

    Article  CAS  PubMed  Google Scholar 

  • Crook M, Couchman S & Tutt P (1996): The relationship between plasma sialic acid and fibrinogen in NIDDM. Coagulation Fibinol. 7, 586–589.

    Article  CAS  Google Scholar 

  • Crook MA, Pickup JC, Lumb PJ & Georgino F (2001): Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes. Diabetes Care 24, 316–322.

    Article  CAS  PubMed  Google Scholar 

  • Crook MA, Tutt P, Simpson H & Pickup JC (1993): Serum sialic acid and acute phase proteins in type 1 and type 2 diabetes mellitus. Clin. Chim. Acta. 219, 131–138.

    Article  CAS  PubMed  Google Scholar 

  • Dewey KG, Peerson JM, Brown KH, Krebs NF, Michaelsen KF, Persson LA, Salmenpera L, Whitehead RG & Yeung DL (1995): Growth of breast-fed infants deviates from current reference data: a pooled analysis of US, Canadian, and European data sets. World Health Organization Working Group on Infant Growth. Pediatrics 96, 495–503.

    Article  CAS  PubMed  Google Scholar 

  • Dickson JJ & Messer M (1978): Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk. Biochem. J. 170, 407–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Downing JA, Wilkinson SJ, Wang B, Brand-Miller J & Bryden WL (2001): Uptake of N-acetylneuraminic acid-6-14C (sialic acid) into the brain of neonatal piglets. Asia Paci. Clin. Nutr. 25, S39.

    Google Scholar 

  • Dreyfus H, Ferret B, Harth S, Gorio A, Durand M, Freysz L & Massarelli R (1984): Metabolism and function of gangliosides in developing neurons. J. Neurosci. Res. 12, 311–322.

    Article  CAS  PubMed  Google Scholar 

  • Ebner KE & Schanbacher FL (1974): Biochemistry of lactose and related carbohydrates. In Lactation: A Comprehensive Treatise, eds. BL Larson & VR Smith, Vol. 2, pp 77–103. New York: Academic Press.

    Google Scholar 

  • Edelfors S (1981): The effect of chronic lithium treatment on the sialic acid content in rat brain synaptosomes. Acta Pharmacol. Toxicol. 48, 61–64.

    Article  CAS  Google Scholar 

  • Elliott PJ, Garofalo L & Cuello AC (1989): Limited neocortical devascularizing lesions causing deficits in memory retention and choline acetyltransferase activity-effects of the monosialoganglioside GM1. Neuroscience 31, 63–76.

    Article  CAS  PubMed  Google Scholar 

  • Engfer MB, Stahl B, Finke B, Sawatzki G & Daniel H (2000): Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am. J. Clin. Nutr. 71, 1589–1596.

    Article  CAS  PubMed  Google Scholar 

  • Esmann M, Marsh D, Schwarzmann G & Sandhoff K (1988): Ganglioside–protein interactions: spin-label electron spin resonance studies with (Na+,K+)-ATPase membranes. Biochemistry 27, 2398–2403.

    Article  CAS  PubMed  Google Scholar 

  • Fagioli S, Castellano C, Oliverio A & Toffano G (1990): Effect of chronic GM1 ganglioside administration on passive avoidance retention in mice. Neurosci. Lett. 109, 212–216.

    Article  CAS  PubMed  Google Scholar 

  • Fergusson DM, Beautrais AL & Silva Pas (1982): Breast-feeding and cognitive development in the first seven years of life. Soc. Sci. Med. 16, 1705–1708.

    Article  CAS  PubMed  Google Scholar 

  • Fernandes de Lima VM, Wiedemann M, Klottig H, Rahmann H & Hanke W (1997): Exogenous application of gangliosides changes the state of excitability of retinal tissue as demonstrated by retinal spreading depression experiments. Naunyn Schmiedebergs Arch. Pharmacol. 355, 507–514.

    Article  CAS  PubMed  Google Scholar 

  • Fong TG, Neff NH & Hadjiconstantinou M (1997): GM1 ganglioside improves spatial learning and memory of aged rats. Behav. Brain. Res. 85, 203–211.

    Article  CAS  PubMed  Google Scholar 

  • Fontaine G, Biserte G, Montreuil J, Dupont A & Farriaux JP (1968): La sialurie: un trouble metabolique original. Helv. Paediatr. Acta. Suppl 17, 1–32.

    Google Scholar 

  • Friede RL (1989): Developmental Neuropathology, pp 2–5. Berlin, New York: Springer-Verlag.

    Book  Google Scholar 

  • Gal B, Ruano MJ, Puente R, Garcia-Pardo LA, Rueda R, Gil A & Hueso P (1997): Developmental changes in UDP-N-acetylglucosamine 2-epimerase activity of rat and guinea-pig liver. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 118, 13–15.

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Segura LM, Martinez-Rodriguez R, Martinez-Murillo R, Bogonez E & Toledano A (1978): Glycoproteins and polyanions in the synapses of rat and mouse central nervous system. Acta. Histochem. 61, 89–97.

    Article  CAS  PubMed  Google Scholar 

  • Gibson RA (1999): Long-chain polyunsaturated fatty acids and infant development. Lancet 354, 1919–1920.

    Article  CAS  PubMed  Google Scholar 

  • Glasier MM, Janis LS, Goncalves MI & Stein DG (1999): GM1 produces attenuation of short-term memory deficits in Hebb–Williams maze performance after unilateral entorhinal cortex lesions. Physiol. Behav. 66, 441–446.

    Article  CAS  PubMed  Google Scholar 

  • Goldman AS & Garza C (1987): Future research in human milk. Pediatr. Res. 22, 493–496.

    Article  CAS  PubMed  Google Scholar 

  • Grantham-McGregor SM, Walker SP & Chang S (2000): Nutritional deficiencies and later behavioural development. Proc. Nutr. Soc. 59, 47–54.

    Article  CAS  PubMed  Google Scholar 

  • Grimmonprez L & Montreuil J (1968): Etude physico-chimique de six nouveaux oligosides isoles du lait de femme. Bull. Soc. Chim. Biol. (Paris) 50, 843–855.

    CAS  Google Scholar 

  • Gronberg G, Lipniunas P, Lundgren T, Erlansson K, Lindh F & Nilsson B (1989): Isolation of monosialyated oligosaccharides from human milk and structural analysis of three new compounds. Carbohydr. Res. 191, 261–278.

    Article  CAS  PubMed  Google Scholar 

  • Gronberg G, Lipniunas P, Lundgren T, Lindh F & Nilsson B (1992): Structural analysis of five new monosialylated oligosaccharides from human milk. Arch. Biochem. Biophys. 296, 597–610.

    Article  CAS  PubMed  Google Scholar 

  • Haverkamp J, Veh RW, Sander M, Schauer R, Kamerling JP & Vliegenthart JG (1977): Demonstration of 9-O-acetyl-N-acetylneuraminic acid in brain gangliosides from various vertebrates including man. Hoppe Seylers Z. Physiol. Chem. 358, 1609–1612.

    Article  CAS  PubMed  Google Scholar 

  • Hayakawa K, De Felice C, Watanabe T, Tanaka T, Iinuma K, Nihei K, Higuchi S, Ezoe T, Hibi I & Kurosawa K (1993): Determination of free N–acetylneuraminic acid in human body fluids by high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. 620, 25–31.

    Article  CAS  PubMed  Google Scholar 

  • Horwood LJ & Fergusson DM (1998): Breastfeeding and later cognitive and academic outcomes. Pediatrics 101, E9.

    Article  CAS  PubMed  Google Scholar 

  • Idota T, Kawakami H, Murakami Y & Sugawara M (1995): Inhibition of cholera toxin by human milk fractions and sialyllactose. Biosci. Biotechnol. Biochem. 59, 417–419.

    Article  CAS  PubMed  Google Scholar 

  • Inokuchi J, Mizutani A, Jimbo M, Usuki S, Yamagishi K, Mochizuki H, Muramoto K, Kobayashi K, Kuroda Y, Iwasaki K, Ohgami Y & Fujiwara M (1997): Up-regulation of ganglioside biosynthesis, functional synapse formation, and memory retention by a synthetic ceramide analog (L-PDMP). Biochem. Biophys. Res. Commun. 237, 595–600.

    Article  CAS  PubMed  Google Scholar 

  • Jensen RG (1995): Handbook of Milk Composition. San Diego:Academic Press.

    Google Scholar 

  • Kario K, Matsuo T, Imiya M, Kayaba K, Kuroda T, Nago N et al (1994): Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects >75 years of age. Am. J. Cardio. 73, 1187–1190.

    Article  CAS  Google Scholar 

  • Karlsson I & Svennerholm L (1978): Biochemical development of rat forebrains in severe protein and essential fatty acid deficiencies. J. Neurochem. 31, 657–662.

    Article  CAS  PubMed  Google Scholar 

  • Karpiak SE & Mahadik SP (1990): Enhanced cortical maturation: gangliosides in CNS plasticity. Prog. Brain Res. 85, 299–308.

    Article  CAS  PubMed  Google Scholar 

  • Kawakami H (1997): Biological significance of sialic acid-containing substances in milk and their application. Agric. Biolo. Chem. 1, 193–208.

    CAS  Google Scholar 

  • Kitagawa H, Nakada H, Numata Y, Kurosaka A, Fukui S, Funakoshi I et al (1990): Occurrence of tetra- and pentasaccharides with the sialyl-Le(a) structure in human milk. J. Biol. Chem. 265, 4859–4862.

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa H, Takaoka M, Nakada H, Fukui S, Funakoshi I, Kawasaki T et al (1991): Isolation and structural studies of human milk oligosaccharides that are reactive with a monoclonal antibody MSW 113. J. Biochem. (Tokyo) 110, 598–604.

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa H, Nakada H, Fukui S, Funakoshi I, Kawasaki T, Yamashina I, et al (1993): Novel oligosaccharides with the sialyl-Le(a) structure in human milk. J. Biochem. 114, 504–508.

    Article  CAS  PubMed  Google Scholar 

  • Kobata A & Ginsburg V (1972a): Oligosaccharides of human milk. 3. Isolation and characterization of a new hexasaccharide, lacto-N-hexaose. J. Biol. Chem. 247, 1525–1529.

    Article  CAS  PubMed  Google Scholar 

  • Kobata A & Ginsburg V (1972b): Oligosaccharides of human milk. IV. Isolation and characterization of a new hexasaccharide, lacto-N-neohexaose. Arch. Biochem. Biophys. 150, 273–281.

    Article  CAS  PubMed  Google Scholar 

  • Kracun I, Rosner H, Cosovic C & Stavljenic A (1984): Topographical atlas of the gangliosides of the adult human brain. J. Neurochem. 43, 979–989.

    Article  CAS  PubMed  Google Scholar 

  • Kuhn R (1959): Biochemie der rezeptoren und resistenzfaktoren. Von der widerstands fahigkeit der lebewesen gegen einwirkungen der umwelt. Naturwissenschaften 46, 43–50.

    Article  Google Scholar 

  • Kuhn R & Brossmer R (1959): Uber das durch viren der influenza-gruppe spaltbare trisaccharid der milch. Chem. Ber. 92, 1667–1671.

    Article  CAS  Google Scholar 

  • Kuhn R & Gauhe A (1965): Bestimmung der bindungsstelle von sialinsaureresten in oligosacchariden mit hilfe von perjodat. Chem. Ber. 98, 395–413.

    Article  CAS  Google Scholar 

  • Kuizenga AB, van Agtmaal EJ, van Haeringen NJ & Kijlstra A (1990): Sialic acid in human tear fluid. Exp. Eye. Res. 50, 45–50.

    Article  CAS  PubMed  Google Scholar 

  • Kunz C & Lönnerdal B (1990): Human-milk proteins: analysis of casein and casein subunits by anion-exchange chromatography, gel electrophoresis, and specific staining methods. Am. J. Clin. Nutr. 51, 37–46.

    Article  CAS  PubMed  Google Scholar 

  • Kunz C & Rudloff S (1993): Biological functions of oligosaccharides in human milk. Acta Paediatr. 82, 903–912.

    Article  CAS  PubMed  Google Scholar 

  • Lanting CI & Boersma ER (1996): Lipids in infant nutrition and their impact on later development. Curr. Opin. Lipidol. 7, 43–47.

    Article  CAS  PubMed  Google Scholar 

  • Ledeen RW (1978): Ganglioside structures and distribution: are they localized at the nerve ending? J. Supramol. Struct. 8, 1–17.

    Article  CAS  PubMed  Google Scholar 

  • Leskawa KC & Rosenberg A (1981): The organization of gangliosides and other lipid components in synaptosomal plasma membranes and modifying effects of calcium ion. Cell Mol. Neurobiol. 1, 373–388.

    Article  CAS  PubMed  Google Scholar 

  • Lindberg G, Rastam L, Gullberg B, Eklund GA & Tornberg S (1991): Serum sialic acid concentration and smoking: a population based study. BMJ 303, 1306–1307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loo YH, Hyde KR, Lin FH & Wisniewski HM (1985): Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins. Life. Sci. 37, 2099–2109.

    Article  CAS  PubMed  Google Scholar 

  • Lucas A, Morley R & Cole TJ (1998): Randomised trial of early diet in preterm babies and later intelligence quotient. BMJ 317, 1481–1487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lucas A, Morley R, Cole TJ, Gore SM, Lucas PJ, Crowle P, Pearse R, Boon AJ & Powell R (1990): Early diet in preterm babies and developmental status at 18 months. Lancet 335, 1477–1481.

    Article  CAS  PubMed  Google Scholar 

  • Lucas A, Morley R, Cole TJ, Lister G & Leeson-Payne C (1992): Breast milk and subsequent intelligence quotient in children born preterm. Lancet 339, 261–264.

    Article  CAS  PubMed  Google Scholar 

  • Makrides M, Neumann MA, Byard RW, Simmer K & Gibson RA (1994): Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am. J. Clin. Nutr. 60, 189–194.

    Article  CAS  PubMed  Google Scholar 

  • Makrides M, Neumann M, Simmer K, Pater J & Gibson R (1995): Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 345,1463–1468.

    Article  CAS  PubMed  Google Scholar 

  • Mancini GM, Hu P, Verheijen FW, van Diggelen OP, Janse HC, Kleijer WJ et al (1992): Salla disease variant in a Dutch patient. Potential value of polymorphonuclear leucocytes for heterozygote detection. Eur. J. Pediatr. 151, 590–595.

    Article  CAS  PubMed  Google Scholar 

  • McVeagh P & Miller JB (1997): Human milk oligosaccharides: only the breast. J. Paediatr. Child. Health 33, 281–286.

    Article  CAS  PubMed  Google Scholar 

  • Menkes JH (1977): Early feeding history of children with learning disorders. Dev. Med. Child Neurol. 19, 169–171.

    Article  CAS  PubMed  Google Scholar 

  • Merat A & Dickerson JW (1973): The effect of development on the gangliosides of rat and pig brain. J. Neurochem. 20, 873–880.

    Article  CAS  PubMed  Google Scholar 

  • Miller MW (1993): Migration of cortical neurons is altered by gestational exposure to ethanol. Alcohol. Clin. Exp. Res. 17, 304–314.

    Article  CAS  PubMed  Google Scholar 

  • Montreuil J, Biserte G, Strecker G, Spik G, Fontaine G & Farriaux JP (1968): Description d'un nouveau type de meliturie: la sialurie. Clin. Chim. Acta. 21, 61–69.

    Article  CAS  PubMed  Google Scholar 

  • Morgan BL (1990): Nutritional requirements for normative development of the brain and behavior. Ann. NY Acad. Sci. 602, 127–132.

    Article  CAS  PubMed  Google Scholar 

  • Morgan BL & Naismith DJ (1982): The effect of early postnatal undernutrition on the growth and development of the rat brain. Br. J. Nutr. 48, 15–23.

    Article  CAS  PubMed  Google Scholar 

  • Morgan BL, Oppenheimer J & Winick M (1981): Effects of essential fatty acid deficiency during late gestation on brain N-acetylneuraminic acid metabolism and behaviour in the progeny. Br. J. Nutr. 46, 223–230.

    Article  CAS  PubMed  Google Scholar 

  • Morgan BL & Winick M (1980a): Effects of administration of N–acetylneuraminic acid (NANA) on brain NANA content and behavior. J. Nutr. 110, 416–424.

    Article  CAS  PubMed  Google Scholar 

  • Morgan BL & Winick M (1980b): Effects of environmental stimulation on brain N-acetylneuraminic acid content and behavior. J. Nutr. 110, 425–432.

    Article  CAS  PubMed  Google Scholar 

  • Mortensen EL, Michaelsen KF, Sanders SA & Reinisch JM (2002): The association between duration of breastfeeding and adult intelligence. JAMA 287(18), 2365–2371.

    Article  PubMed  Google Scholar 

  • Neeser JR, Golliard M & Del Vedovo S (1991): Quantitative determination of complex carbohydrates in bovine milk and in milk-based infant formulas. J. Dairy Sci. 74, 2860–2871.

    Article  CAS  PubMed  Google Scholar 

  • Newburg DS (1999): Human milk glycoconjugates that inhibit pathogens. Curr. Med. Chem. 6, 117–127.

    Article  CAS  PubMed  Google Scholar 

  • Newburg DS (2000): Oligosaccharides in human milk and bacterial colonization. J. Pediatr. Gastroenterol. Nutr. 30(Suppl 2), S8–S17.

    Article  CAS  PubMed  Google Scholar 

  • Newburg DS & Neubauer SH (1995): Carbohydrates in milks: analysis, quantities, and significance. In Handbook of Milk Composition. ed. RG Jensen, pp 273–338. San Diego: Academic Press.

    Chapter  Google Scholar 

  • Nöhle U & Schauer R (1981): Uptake, metabolism and excretion of orally and intravenously administered, 14C- and 3H-labeled N-acetylneuraminic acid mixture in the mouse and rat. Hoppe Seylers Z. Physiol. Chem. 362,1495–1506.

    Article  PubMed  Google Scholar 

  • Ounsted M, Moar VA, Cockburn J & Redman CW (1984): Factors associated with the intellectual ability of children born to women with high risk pregnancies. Br. Med. J. (Clin. Res. Ed.) 288, 1038–1041.

    Article  CAS  Google Scholar 

  • Pan XL & Izumi T (2000): Variation of the ganglioside compositions of human milk, cow's milk and infant formulas. Early Hum. Dev. 57, 25–31.

    Article  CAS  PubMed  Google Scholar 

  • Parkkinen J & Finne J (1987): Method in Enzymology, p 289. New York: Academic press.

    Google Scholar 

  • Parkkinen J, Finne J, Achtman M, Vaisanen V & Korhonen TK (1983): Escherichia coli strains binding neuraminyl alpha 2–3 galactosides. Biochem. Biophys. Res. Commun. 111, 456–461.

    Article  CAS  PubMed  Google Scholar 

  • Poduslo JF & Curran GL (1994): Glycation increases the permeability of proteins across the blood-nerve and blood-brain barriers. Brain Res. Mol. Brain Res. 23, 157–162.

    Article  CAS  PubMed  Google Scholar 

  • Puente R & Hueso P (1993): Lactational changes in the N-glycoloylneuraminic acid content of bovine milk gangliosides. Biol. Chem. Hoppe Seyler. 374, 475–478.

    Article  CAS  PubMed  Google Scholar 

  • Rahmann H (1989): Calcium–ganglioside interactions as modulators for synaptic transmission and long-term neuronal adaptation (memory). Fortschr Zool. 37, 349–368.

    CAS  Google Scholar 

  • Rahmann H & Rahmann M (1992): The Neurobiological Basis of Memory and Behavior. New York: Springer-Verlag.

    Book  Google Scholar 

  • Renlund M, Tietze F & Gahl WA (1986): Defective sialic acid egress from isolated fibroblast lysosomes of patients with Salla disease. Science 232, 759–762.

    Article  CAS  PubMed  Google Scholar 

  • Reuter G & Gabius HJ (1996): Sialic acids structure-analysis metabolism-occurrence-recognition. Biol. Chem. Hoppe Seyler. 377, 325–342.

    Article  CAS  PubMed  Google Scholar 

  • Richards M, Wadsworth M, Rahimi-Foroushani A, Hardy R, Kuh D & Paul A (1998): Infant nutrition and cognitive development in the first offspring of a national UK birth cohort. Dev. Med. Child Neurol. 40, 163–167.

    CAS  PubMed  Google Scholar 

  • Rodgers B (1978): Feeding in infancy and later ability and attainment: a longitudinal study. Dev. Med. Child Neurol. 20, 421–426.

    Article  CAS  PubMed  Google Scholar 

  • Rogan WJ & Gladen BC (1993): Breast-feeding and cognitive development. Early Hum. Dev. 31, 181–193.

    Article  CAS  PubMed  Google Scholar 

  • Romer H & Rahmann H (1979): Effects of exogenous neuraminidase on unit activity in frog spinal cord and fish optic tectum. Exp. Brain Res. 34, 49–58.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg A (1995): Biology of the Sialic Acids. New York: Plenum Press.

    Book  Google Scholar 

  • Rosenberg A & Noble EP (1994): Ethanol attenuation of ganglioside sialylation and neuritogenesis. Alcohol 11, 565–569.

    Article  CAS  PubMed  Google Scholar 

  • Rudloff S & Kunz C (1997): Protein and nonprotein nitrogen components in human milk, bovine milk, and infant formula: quantitative and qualitative aspects in infant nutrition. J. Pediatr. Gastroenterol. Nutr. 24, 328–344.

    Article  CAS  PubMed  Google Scholar 

  • Rueda R, Garcia-Salmeron JL, Maldonado J & Gil A (1996a): Changes during lactation in ganglioside distribution in human milk from mothers delivering preterm and term infants. Biol. Chem. 377, 599–601.

    CAS  PubMed  Google Scholar 

  • Rueda R, Maldonado J & Gil A (1996b): Comparison of content and distribution of human milk gangliosides from Spanish and Panamanian mothers. Ann. Nutr. Metab. 40, 194–201.

    Article  CAS  PubMed  Google Scholar 

  • Sadoul R, Hirn M, Deagostini-Bazin H, Rougon G & Goridis C (1983): Adult and embryonic mouse neural cell adhesion molecules have different binding properties. Nature 304, 347–349.

    Article  CAS  PubMed  Google Scholar 

  • Salvolini E, Di Giorgio R, Curatola A, Mazzanti L & Fratto G (1998): Biochemical modifications of human whole saliva induced by pregnancy. Br. J. Obstet. Gynaecol. 105, 656–660.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Diaz A, Ruano MJ, Lorente F & Hueso P (1997): A critical analysis of total sialic acid and sialoglycoconjugate contents of bovine milk-based infant formulas. J. Pediatr. Gastroenterol. Nutr. 24, 405–410.

    Article  CAS  PubMed  Google Scholar 

  • Sandra D, Frisson S & Daems F (1999): Why simple verb forms can be so difficult to spell: the influence of homophone frequency and distance in Dutch. Brain Lang. 68, 277–283.

    Article  CAS  PubMed  Google Scholar 

  • Schauer R (1982): Sialic Acids, Chemistry, Metabolism, and Function. Wien, New York: Springer-Verlag.

    Book  Google Scholar 

  • Schauer R & Kamerling JP (1997): Chemistry, biochemistry and biology of sialic acids. In Glycoproteins II, ed. H Schachter, J Montreuil & JFG Vliegenthart, Vol. 19B, pp 243–372. Amsterdam, New York:Elsevier.

    Chapter  Google Scholar 

  • Schauer R, Kelm S, Reuter G & Roggentin P (1995): Biochemistry and role of sialic acid. In Biology of the Sialic Acids, ed. A Rosenberg, pp 7–49. New York: Plenum Press.

    Chapter  Google Scholar 

  • Schengrund CL & Mummert CM (1998): Exogenous gangliosides. How do they cross the blood-brain barrier and how do they inhibit cell proliferation. Ann. N Y Acad. Sci. 845, 278–284.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt R (1989): Glycoproteins involved in long-lasting plasticity in the teleost brain. Fortschr. Zool. 37, 327–339.

    CAS  Google Scholar 

  • Seppala R, Tietze F, Krasnewich D, Weiss P, Ashwell G, Barsh G, Thomas GH, Packman S & Gahl WA (1991): Sialic acid metabolism in sialuria fibroblasts. J. Biol. Chem. 266, 7456–7461.

    Article  CAS  PubMed  Google Scholar 

  • Shaw L & Schauer R (1988): The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol. Chem. Hoppe Seyler 369, 477–486.

    Article  CAS  PubMed  Google Scholar 

  • Shen Z, Warren CD & Newburg DS (2000): High-performance capillary electrophoresis of sialylated oligosaccharides of human milk. Anal. Biochem. 279, 37–45.

    Article  CAS  PubMed  Google Scholar 

  • Silva RH, Bergamo M, Vital BB & Frussa-Filho R (1998): Effects of neonatal GM1 administration on the discriminative avoidance behavior of adult rats. Ann. NY Acad. Sci. 845, 425.

    Article  CAS  PubMed  Google Scholar 

  • Silva RH, Felicio LF & Frussa-Filho R (1999): Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice. Psychopharmacology 141, 111–117.

    Article  CAS  PubMed  Google Scholar 

  • Silva RH, Felicio LF, Nasello AG, Vital MA & Frussa-Filho R (1996): Effect of ganglioside (GM1) on memory in senescent rats. Neurobiol. Aging 17, 583–586.

    Article  CAS  PubMed  Google Scholar 

  • Smith DF, Prieto PA, McCrumb DK & Wang WC (1987): A novel sialylfucopentaose in human milk. Presence of this oligosaccharide is not dependent on expression of the secretor or Lewis fucosyltransferases. J. Biol. Chem. 262, 12040–12047.

    Article  CAS  PubMed  Google Scholar 

  • Sorbi S, Piacentini S & Amaducci L (1987): Intralaminar distribution of neurotransmitter-related enzymes in cerebral cortex of Alzheimer's disease. Gerontology 33, 197–202.

    Article  CAS  PubMed  Google Scholar 

  • Spik G, Strecker G, Fournet B, Bouquelet S, Montreuil J, Dorland L et al (1982): Primary structure of the glycans from human lactotransferrin. Eur. J. Biochem. 121, 413–419.

    Article  CAS  PubMed  Google Scholar 

  • Sturman JA, Lin YY, Higuchi T & Fellman JH (1985): N-acetylneuramin lactose sulfate: a newly identified nutrient in milk. Pediatr. Res. 19, 216–219.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki K (1965): The pattern of mammalian brain gangliosides. II. Evaluation of the extraction procedures, postmortem changes and the effect of formalin preservation. J. Neurochem. 12, 629–638.

    Article  CAS  PubMed  Google Scholar 

  • Svennerholm L (1980): Structure and biology of cell membrane gangliosides. Cholera and Related Diarrheas: Molecular Aspects of a Global Health Problem: 43rd Nobel Symposium, Stockholm, August 6–11, 1978, eds Ouchterlony & J Holmgren, pp 5–251. WHO & Nobelstiftelsen, Basel; New York:S. Karger.

    Google Scholar 

  • Svennerholm L, Bostrom K, Fredman P, Mansson JE, Rosengren B & Rynmark BM (1989): Human brain gangliosides: developmental changes from early fetal stage to advanced age. Biochim. Biophys. Acta. 1005, 109–117.

    Article  CAS  PubMed  Google Scholar 

  • Svennerholm L, Bostrom K, Jungbjer B & Olsson L (1994): Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem 63, 1802–1811.

    Article  CAS  PubMed  Google Scholar 

  • Taniuchi K, Chifu K, Hayashi N, Nakamachi Y, Yamaguchi N, Miyamoto Y et al (1981): A new enzymatic method for the determination of sialic acid in serum and its application for a marker of acute phase reactants. Kobe J. Med. Sci. 27, 91–102.

    CAS  PubMed  Google Scholar 

  • Tram TH, Brand Miller JC, McNeil Y & McVeagh P (1997): Sialic acid content of infant saliva: comparison of breast fed with formula fed infants. Arch. Dis. Child 77, 315–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Troy FAI (1995): Sialobiology and the polysialic acid glycotope: occurrence, structure, function, synthesis, and glycopathology. In Biology of the Sialic Acids. ed. A Rosenberg, Vol. xv, p 378. New York: Plenum Press.

    Google Scholar 

  • Uauy R & Peirano P (1999): Breast is best: human milk is the optimal food for brain development. Am. J. Clin. Nutr. 70, 433–434.

    Article  CAS  PubMed  Google Scholar 

  • Uauy R, Mena P & Peirano P (2001): Mechanisms for nutrient effects on brain development and cognition. Nestle Nutr. Workshop Ser. Clin. Perform. Program 5, 41–70.

    Article  CAS  Google Scholar 

  • Ueno K, Ando S & Yu RK (1978): Gangliosides of human, cat, and rabbit spinal cords and cord myelin. J. Lipid. Res. 19, 863–871.

    Article  CAS  PubMed  Google Scholar 

  • Urashima T, Saito T, Nakamura T & Messer M (2001): Oligosaccharides of milk and colostrum in non-human mammals. Glycocon. J. 18, 357–371.

    Article  CAS  Google Scholar 

  • Varki A (1992): Diversity in the sialic acids [published erratum appears in Glycobiology 1992 Apr;2(2):following 168]. Glycobiology 2, 25–40.

    Article  CAS  PubMed  Google Scholar 

  • Varki A (1993): Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3, 97–130.

    Article  CAS  PubMed  Google Scholar 

  • Varki A, Cummings R, Kesko J, Freeze H, Hart G & Marth J (1999): Sialic acids. In The Essentials of Glycobiology, eds A Varki, R Cummings, J Kesko, et al, pp 195–209. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Varki A & Diaz S (1984): The release and purification of sialic acids from glycoconjugates: methods to minimize the loss and migration of O-acetyl groups. Anal. Biochem. 137, 236–247.

    Article  CAS  PubMed  Google Scholar 

  • Veh RW, Michalski JC, Corfield AP, Sander-Wewer M, Gies D & Schauer R (1981): New chromatographic system for the rapid analysis and preparation of colostrum sialyloligosaccharides. J. Chromatogr. 212, 313–322.

    Article  CAS  PubMed  Google Scholar 

  • von Itzstein M & Thomson RJ (1997): Sialic acids and sialic acid-recognising proteins: drug discovery targets and potential glycopharmaceuticals. Curr. Med. Chem. 4, 185–210.

    Article  CAS  Google Scholar 

  • Wakabayashi I, Sakamoto K, Yoshimoto S & Masui H (1992): Relation of serum sialic acid to lipid concentrations. BMJ 305, 562–563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang B, Brand Miller J, McNeil Y & McVeagh P (1998): Sialic acid concentration of brain gangliosides: Variation among eight mammalian species. Comp. Biochem. Physiol. 119A(1), 435–439.

    Article  CAS  Google Scholar 

  • Wang B, Brand Miller J, Sun Y, Ahmad Z, McVeagh P & Petocz P (200la): A longitudinal study of salivary sialic acid in preterm infants: comparison of human milk-fed vs formula-fed infants. J. Pediatr. 138, 914–916.

    Article  Google Scholar 

  • Wang B, Brand-Miller J, McVeagh P & Petocz P (2001b): The concentration and distribution of sialic acid in human milk vs infant formulas. Am. J. Clin. Nutr. 74, 510–515.

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Brand-Miller J, McVeagh P & Petocz P (2001c): Brain sialic acid concentration: comparison of breast-fed vs formula-fed infants. Asia. Pacific. J. Clin. Nutr. 10(suppl): S33.

    Google Scholar 

  • Warren L (1994): Bound Carbohydrates in Nature. Cambridge; New York, NY, USA: Cambridge University Press.

    Book  Google Scholar 

  • Waters PJ, Lewry E & Pennock CA (1992): Measurement of sialic acid in serum and urine: clinical applications and limitations. Ann. Clin. Biochem. 29, 625–637.

    Article  CAS  PubMed  Google Scholar 

  • Wiegandt H (1994): Principles of glycosphingolipid-oligosaccharide constitution. Prog. Brain. Res. 101, 63–73.

    Article  CAS  PubMed  Google Scholar 

  • Wieruszeski JM, Chekkor A, Bouquelet S, Montreuil J, Strecker G, Peter-Katalinic J & Egge H (1985): Structure of two new oligosaccharides isolated from human milk: sialylated lacto-N-fucopentaoses I and II. Carbohydr. Res. 137, 127–138.

    Article  CAS  PubMed  Google Scholar 

  • Yamashita K, Tachibana Y & Kobata A (1976): Oligosaccharides of human milk. Isolation and characterization of three new disialyfucosyl hexasaccharides. Arch. Biochem. Biophys. 174, 582–591.

    Article  CAS  PubMed  Google Scholar 

  • Yamashita K, Tachibana Y & Kobata A (1977): Oligosaccharides of human milk: structures of three lacto-N-hexaose derivatives with H-haptenic structure. Arch. Biochem. Biophys. 182, 546–555.

    Article  CAS  PubMed  Google Scholar 

  • Yu RK, Macala LJ, Farooq M, Sbaschnig-Agler M, Norton WT & Ledeen RW (1989): Ganglioside and lipid composition of bulk-isolated rat and bovine oligodendroglia. J. Neurosci. Res. 23, 136–141.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, B., Brand-Miller, J. The role and potential of sialic acid in human nutrition. Eur J Clin Nutr 57, 1351–1369 (2003). https://doi.org/10.1038/sj.ejcn.1601704

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601704

Keywords

This article is cited by

Search

Quick links