Importance of "Sialic Acid" in infant nutrition

The term "Sialic Acid" is used for one of the monosaccharides in the human body whose chemical name is "N-acetyl D-neuraminic acid" (NANA). The term Sialic Acids (Sia) refers to a family of monosaccharides having more than 60 members and all derived from "D-neuraminic acid" (9-carbon sugar) (figure below).

In 1952, Kuhn (awarded the Nobel Prize in Chemistry in 1938 for research on carotenoids and vitamins) named milk saccharides "milk vitamins".

"Sialic Acids" are bioactive compounds present in human milk. 100 ml of human milk contain 9-155 mg of Sialic Acid. The differences in these numbers are due to a variety of reasons, including lactation period and testing method.

Biosynthesis of "Sialic Acid" in the body:

"Sialic Acid" is made in human body, but at times, such as during learning and development of the brain, as well as during infancy (due to the lack of activity of the constitutive enzymes of "Sialic Acid"), the needed amount of "Sialic Acid" is greater than the amount made in the body. So Sialic Acid must be provided by feeding.

The amount of "Sialic Acid" in different liquids and tissues:

The highest concentrations of “Sialic Acid” are in colostrum (879-1872 mg/l), infant feces fed with breast milk (412-1977 mg/l), gray matter (481- 1067 mg/l), human milk (1122-208 mg/l), white matter (453-275 mg/l), saliva (253-32 mg/l) respectively.

Sometimes the amount of "Sialic Acid" which is needed is greater than the amount made in the body, such as:

1. Pregnancy and lactation

During different lactation periods, the amount of "Sialic Acid" also varies, with the highest amount in colostrum (figure below).

Breast milk for preterm infants also contains higher levels of "Sialic Acid" than infants. Also, feces, brains, and saliva of infants fed with breast milk had higher levels of "Sialic Acid" than infants. These observations show that the breastfed baby is able to use the "Sialic Acid" in the diet. Therefore, the benefits of breast milk can be achieved by enriching the formula with "Sialic Acid".
Research has shown that the amount of "Sialic Acid" in the saliva of pregnant women decreases as pregnancy progresses and rapidly returns to normal after delivery. So the need for "Sialic Acid" in this period is increasing.

Research has shown that the concentration of "Sialic Acid" in the serum and the red blood cell membrane in healthy pregnant women increases markedly as pregnancy progresses, and continues to increase for up to 12 weeks after delivery.

Lack or absence of "Sialic Acid" in the fetal tissue reduces placental function. Consequently, it affects the development of embryonic vessels and the efficiency of the placenta in material exchange between the fetus and the mother. This may lead to a decrease in fetal growth and development.

During pregnancy, the amount of "Sialic Acid" in the saliva increases. The rate of "Sialic Acid" rises from 54 mg/l in the tenth week of pregnancy to 150 mg/l in the 21st week and 130 mg/l in the 40th week. Simultaneously, accumulation of "Sialic Acid" in the fetal brain also increases. The amount of "Sialic Acid" in urine reaches to 32 mmol/mol at the 12th week of gestation.  The amount of "Sialic Acid" in urine reaches to 54 mmol/mol from 26th week to 40th week. This value remains constant for up to 2 weeks after childbirth. The amount of "Sialic Acid" reaches in amniotic fluid 965 in the second trimester and 1458 in the third trimester, and 1802 postpartum. Based on this information, it can be concluded that in a healthy pregnant mother, there is always sufficient "Sialic Acid" to feed the fetus.


2. Aging

Research has shown that the amount of "Sialic Acid" in the brain increases from infancy to 40 years old and gradually declines after 60 (drastically decreases above age 90).

Sialic Acid in human milk

Human milk is the best food for newborns, but when breastfeeding is not possible, bottle feeding is replaced. Most "Sialic Acid" (69-76%) in milk is bonded to "oligosaccharides". 21-28% of "Sialic Acid" in milk is bonded to proteins and about 3% is free and bounded to "gangliosides".


The role of Sialic Acid in the cognitive development

Consideration to "Sialic Acid" as a nutrient to enhance the cognitive development originates from the discovery of "Sialic Acid" in the brain tissue (especially the gray cortex). Sialic Acid plays an important role in brain development and function.

The results of study on 1021 babies (in the New Zealand) from birth to 18 years old showed that IQ scores, standardized tests, teacher evaluation, and school performance in infants who were breastfed is higher than infants fed with normal formula (not enriched with Sialic Acid). Also, the longer the lactation period is, the higher the scores on these assessments are. This is due to the presence of "Sialic Acid" in breast milk.


Importance of Sialic Acid in brain development

Initial brain growth is faster than all other organs and tissues of the body, and by 2 years old, the infant’s brain weight is about 80% of an adult's brain weight. Because of the rapid growth of the brain in newborns, there is an urgent need for nutrients and precursors to build new tissues and cell growth. Malnutrition during this crucial period (early stages of brain development) leads to adverse effects on cognition and comprehension performance in adulthood. Breast milk contains unique nutrients for optimal brain growth and proper functioning. Many of these compounds are not found in cow's milk and infant formula. One of these important nutrients is "Sialic Acid". "Sialic Acid" is an important monosaccharide unit in "gangliosides", brain glycoproteins, and "polysialic Acid". "Sialic Acid" is an important compound of human milk oligosaccharides that are essential for brain development and perception.

"Sialic Acid" is present in all human tissues and is higher in the central nervous system. The amount of "Sialic Acid" in nerve cell membranes is 20 times as much as other cell membranes. Human brain gangliosides make up 6 to 10% of all brain fat.

"Gangliosides" consist of "Glycosphingolipids" (ceramide + oligosaccharides) and one or more units of "Sialic Acid" (attached to the sugar chains). The name of the compounds derives from brain ganglion cells because they were first found in these cells. More than 200 types of "gangliosides" have been identified so far, the difference is mainly in the number and position of "Sialic Acid". "Gangliosides" are amphipathic molecules that contain hydrophobic moiety (ceramide) and hydrophilic moiety (oligosaccharide chains containing "Sialic Acid"). The biological properties of "gangliosides" are most affected by their oligosaccharide part.


The role of Sialic Acid in the immune system

"Sialic Acid" plays an important role in the immune system and also acts as a prey for invading pathogens. By adhering to pathogens, they excrete them through the intestine and prevent disease.


The role of Sialic Acid in nutrient absorption

"Sialic Acid" plays an important role in the absorption of minerals and vitamins. By binding "Sialic Acid" to nutrients, they are absorbed more rapidly through the intestine.


Antioxidant role of Sialic Acid

The researchers reported that free "Sialic Acid" in the physiological condition consumes the toxic substance of hydrogen peroxide using a radical mechanism. In 2009, researchers reported that the reaction between free "Sialic Acid" and "lipid hydroperoxides" also took place. Lipid hydroperoxides, through a variety of reactive oxygen species, cause oxidative stress and are involved in inflammatory processes such as arteriosclerosis.

The antioxidant property of "Sialic Acid" allows it to be used in diseases that have an important role in oxidative stress, such as type 2 diabetes, cancer and aging.

Prebiotic role of Sialic Acid

The prebiotic activity of "Sialic Acid" is a hypothesis, although there is some evidence. Bacterial neuraminidases (such as bifidobacterium bifidum) are present in the human intestine. These enzymes release "Sialic Acid" and give it to useful intestinal bacteria. Accordingly, the potential prebiotic activity of "Sialic Acid" on "bifidobacter" species has been proposed.


References

Bing Wang. 2009. Sialic Acid Is an Essential Nutrient for Brain Development and Cognition. Annu. Rev. Nutr. 29:177–222.

Yang P, Major D, Rutishauser U. 1994. Role of charge and hydration in effects of polysialic acid on molecular interactions on and between cell membranes. J. Biol. Chem. 269:23039–44.

Christoph H. Röhrig, Sharon S. H. Choi & Nigel Baldwin (2015): The Nutritional Role of Free Sialic Acid, a Human Milk Monosaccharide, and Its Application as a Functional Food Ingredient, Critical Reviews in Food Science and Nutrition.

NEYRA, C., PALADINO, J. & LE BORGNE, M. 2014. Oxidation of sialic acid using hydrogen peroxide as a new method to tune the reducing activity. Carbohydr. Res., 38692-98.

LEE, H., GARRIDO, D., MILLS, D. A. & BARILE, D. 2014. Hydrolysis of milk gangliosides by infant-gut associated bifidobacteria determined by microfluidic chips and high-resolution mass spectrometry. Electrophoresis, Epub ahead of print.

Claumarchirant, Lorena, et al. "Evaluation of Sialic Acid in Infant Feeding: Contents and Bioavailability." Journal of agricultural and food chemistry 64.44 (2016): 8333-8342.

Varki, Ajit, and Pascal Gagneux. "Multifarious roles of sialic acids in immunity." Annals of the New York Academy of Sciences 1253.1 (2012): 16-36.