The role and potential of sialic acid in human nutrition
〖 09/19,2018 | Hits 1306 〗


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.



The rapid growth and development of the newborn infant puts exceptional demands on the supply of nutrients. Any deficit has profound effects on somatic growth and organ structural and functional development, especially the brain. Brain growth, including cell number, organ structural and synaptic connectivity, etc, reaches its peak at 26 weeks gestation and then continues at a high rate throughout the first year of life (Uauy and Peirano, 1999Uauy et al, 2001). The rapid initial growth of the brain exceeds that of other body tissues. At 6th month gestation, it comprises 21% of total body weight and 15% at term (Friede, 1989). The brain weight more than doubles during the first 9 postnatal months to reach over 90% of the adult weight by the 6th year. Once the time for the critical period of brain growth has passed, it cannot be restarted. The challenge is accentuated in the premature infants, particularly in relation to nutritional support for brain growth.

Recently, neurodevelopmental research has focused attention on the role of long-chain polyunsaturated fatty acids (LCPUFAs), and particularly docosahexaenoic acid (DHA) in improving visual acuity and cognitive ability in preterm infants (Carlson et al, 1996Gibson, 1999). There are many factors, however, that may support brain growth. One promising new candidate is sialic acid (also known as N-acetylneuraminic acid), a nine-carbon sugar that is a structural and functional component of brain gangliosides and correlates with the amounts of DHA and total long-chain polyunsaturated fatty acids in the ceramide tail of brain gangliosides. Sialic acid may be a conditionally essential nutrient in infancy, if demand outstrips the rate of endogenous synthesis.

Breastfeeding and cognition

Several studies show that children who were breast-fed as babies attain higher scores on intelligence tests than those who were bottle-fed (Rodgers, 1978; Fergusson et al, 1982; Lucas et al, 19921998). On average, scores are 2–9 points higher, a difference that is considered biologically significant. The difference becomes more pronounced as the duration of breastfeeding increases (Dewey et al, 1995). Lucas et al (1992) reported that preterm infants fed human milk in the first month of life have an 8-point advantage in verbal IQ at 7–8 y of age compared with infants fed standard infant formulas. In a large cohort study of several thousand adults, sentence completion, reading ability, and vocabulary were all related to patterns of infant feeding (Richards et al, 1998). In a retrospective study, Menkes (1977) found a significantly greater incidence of bottle feeding among learning-disabled children than among controls being followed for other neurological symptoms. Rodgers (1978) described a large, stratified sample of British children. Covariates included social class, parental interest in education, material home conditions, parental education, family size and birth rank, and age at weaning. After control of confounding variables, there was a significant advantage to breast-fed children on a picture vocabulary test at 8 y of age and on nonverbal ability, mathematics, and sentence completion at 15 y. A few studies have examined reading ability or school attainment, and breast-fed children tended to do better (Ounsted et al, 1984Rogan & Gladen, 1993Horwood & Fergusson, 1998). The most recent follow-up study in a New Zealand cohort of 1000 children reported that breastfeeding is associated with small but detectable increases in cognitive ability and academic achievement, extending from 8 to 18 y (Horwood & Fergusson, 1998). The difference was significant after adjustment for social and family history, including maternal age, education, social economic status, marital status, smoking during pregnancy, family living conditions, and family income, and perinatal factors, including gender, birth weight, child's estimated gestational age, and birth order in the family. Not all studies yield significant differences after adjustment (Sandra et al, 1999). A meta-analysis of 20 controlled studies showed that breastfeeding was associated with a 3.2 point higher cognitive development score than formula feeding after adjusting for significant covariates. The IQ advantage increased with duration of breastfeeding, reaching a plateau at 4–6 months of age. Low birth weight infants received the greatest benefits (Anderson et al, 1999). More recently, Mortensen et al (2002)also reported that duration of breastfeeding was associated with significantly higher scores on all components of the Wechsler adult intelligence scale.

There is little direct evidence for a causative mechanism whereby breastfeeding might enhance or, conversely, bottle feeding might impair cognitive growth. Rodgers (1978) suggested possible mediating factors might be differences between breast and bottle milk osmotic load or protein and lipid concentrations or differences in the feeding situation such as infection risk and psychological effects. Menkes (1977) proposed that tyrosinemia due to increased protein levels in formula milk might produce an increased incidence of learning disabilities in bottle-fed children. Improved maternal–child interaction and reduced morbidity could account for the effect or contribute to it (Grantham-McGregor et al, 2000). Interpretation is further complicated by associations between breastfeeding, social status and education of parents. Women who make a decision to breastfeed are often better educated with positive health attitudes concerning immunisation and smoking, and may provide a more desirable environment for their young to develop intellectually (Lucas et al, 19901992). Statistical adjustment for these associations may not remove the full confounding effect of all these factors.

It is highly possible that any benefit from breastfeeding is due to the unique nutritional content of human milk. Since the brain is undergoing rapid development during the first few weeks or months after birth, not only in anatomic terms but also in physiological, biochemical, and psychological parameters, early nutrition may modulate nervous system development. Infant formulas are the sole source of nutrition for infants who are not breast-fed and differences between them may be important. In a randomised multicenter study (Lucas et al, 1990), preterm infants fed a standard term formula for 1 month performed more poorly at 18 months than those given a nutrient-enriched preterm formula. Those infants given the enriched formula had 15 points higher score than those infants given standard term formula. Recently, neurodevelopmental research has focused on the role of LCPUFAs, and particularly, docosahexaenoic acid (DHA) (Makrides et al, 19941995Lanting & Boersma, 1996). Clinical studies in which infant formula was supplemented with DHA suggested possible improvements in visual acuity and cognitive ability in preterm infants (Carlson et al, 19941996). Infants fed with formula containing DHA had significantly better visual-evoked potential scores than infants fed with control formula without DHA at both 16 and 30 weeks (Makrides et al, 1995). DHA may be the limiting factor in milk formula because the brain, in particular the visual cortex, lays down large amounts in the first year of life. However, if diet is a key to mental development, then there are many factors besides DHA that may be important, such as enzymes, hormones, growth factors, and sialic acid, which are found in human milk but poorly represented in the milk of other species and in infant formulas (Goldman & Garza, 1987). Of these, sialic acid is most intriguing because of its simultaneous presence in large amounts in both human milk and human grey matter.

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