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Nutritional and Physiologic Significance of Human Milk Proteins1–4

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Nutritional and Physiologic Significance of Human Milk Proteins1–4 Nutritional and physiologic significance of human milk proteins1–4 Bo Lönnerdal ABSTRACT NUTRITIONAL ASPECTS OF HUMAN MILK PROTEINS Human milk contains a wide variety of proteins that contribute to The protein content of human milk decreases rapidly during its unique qualities. Many of these proteins are digested and pro- the first month of lactation (1) and declines much more slowly vide a well-balanced source of amino acids to rapidly growing after that. Most proteins are synthesized by the mammary gland, infants. Some proteins, such as bile salt–stimulated lipase, amy- with a few possible exceptions, such as serum albumin (which ␤ ␣ lase, -casein, lactoferrin, haptocorrin, and 1-antitrypsin, assist appears from the maternal circulation). Milk proteins can be clas- in the digestion and utilization of micronutrients and macronutri- sified into 3 groups: mucins, caseins, and whey proteins. Mucins, ents from the milk. Several proteins with antimicrobial activity, also known as milk fat globule membrane proteins, surround the such as immunoglobulins, ␬-casein, lysozyme, lactoferrin, hapto- lipid globules in milk and contribute only a small percentage of corrin, ␣-lactalbumin, and lactoperoxidase, are relatively resist- the total protein content of human milk (2). Because the fat con- ant against proteolysis in the gastrointestinal tract and may, in tent of human milk does not vary during the course of lactation, intact or partially digested form, contribute to the defense of the milk mucin concentration is most likely constant, although breastfed infants against pathogenic bacteria and viruses. Prebi- little information is available concerning this topic. The contents otic activity, such as the promotion of the growth of beneficial of casein and whey proteins, however, change profoundly early in bacteria such as Lactobacilli and Bifidobacteria, may also be pro- lactation; the concentration of whey proteins is very high, vided by human milk proteins. This type of activity can limit the whereas casein is virtually undetectable during the first days of growth of several pathogens by decreasing intestinal pH. Some lactation (3, 4). Subsequently, casein synthesis in the mammary proteins and peptides have immunomodulatory activities (eg, gland and milk casein concentrations increase, whereas the con- cytokines and lactoferrin), whereas others (eg, insulin-like growth centration of total whey proteins decreases, partially because of factor, epidermal growth factor, and lactoferrin) are likely to be an increased volume of milk being produced (Figure 1). As a involved in the development of the intestinal mucosa and other consequence, there is no “fixed” ratio of whey to casein in human organs of newborns. In combination, breast-milk proteins assist milk; it varies throughout lactation (Figure 2). The frequently in providing adequate nutrition to breastfed infants while simul- cited ratio of 60:40 is an approximation of the ratio during the taneously aiding in the defense against infection and facilitating normal course of lactation, but it does vary from Ϸ80:20 in early optimal development of important physiologic functions in new- lactation to 50:50 in late lactation. Because the amino acid com- borns. Am J Clin Nutr 2003;77(suppl):1537S–43S. positions of caseins and whey proteins differ, the amino acid con- tent of human milk also varies during lactation. This is rarely con- KEY WORDS Human milk, breast milk, milk proteins, sidered when estimating requirements. casein, whey proteins, lactoferrin, immunoglobulins, lactoperoxidase, The true protein content of human milk is often overestimated haptocorrin, lysozyme, ␣-lactalbumin because of the high proportion of nonprotein nitrogen (NPN) in human milk (5). The fraction of NPN is low (< 5%) in the milk of most species, which allows a fairly accurate estimation of the true INTRODUCTION milk protein content by total nitrogen analysis. The true milk pro- tein content is estimated by multiplying the nitrogen content of There is no doubt that the proteins in human milk provide an the milk by a dairy protein conversion factor of 6.38, which takes important source of amino acids to rapidly growing breastfed into account such a fraction of NPN. In human milk, however, infants. However, many human milk proteins also play a role in facilitating the digestion and uptake of other nutrients in breast milk. Examples of such proteins are bile salt–stimulated lipase and amylase, which may aid lipid and starch digestion, and 1 From the Departments of Nutrition and Internal Medicine, University of ␤-casein, lactoferrin, and haptocorrin, which may assist in the California, Davis. 2 Presented at the symposium Innovaciones en Fórmulas Infantiles (Inno- absorption of calcium, iron, and vitamin B-12, respectively. vations in Infant Formula), held in Cancun, Mexico, May 23–24, 2002. Human milk proteins also exert numerous physiologic activities, 3 The author’s participation in this symposium was underwritten by Wyeth benefiting breastfed infants in a variety of ways. These activities Nutrition, Philadelphia. include enhancement of immune function, defense against patho- 4 Reprints not available. Address correspondence to B Lönnerdal, Depart- genic bacteria, viruses and yeasts, and development of the gut and ment of Nutrition, University of California, Davis, One Shields Avenue, Davis, its functions. CA 95616. E-mail: [email protected]. Am J Clin Nutr 2003;77(suppl):1537S–43S. Printed in USA. © 2003 American Society for Clinical Nutrition 1537S Downloaded from https://academic.oup.com/ajcn/article-abstract/77/6/1537S/4689886 by guest on 11 January 2018 1538S LÖNNERDAL ᭿ FIGURE 1. Changes in whey protein ( ) and casein ( ) concentrations FIGURE 2. Changes in casein content as a percentage of total protein during lactation in one mother. Data from reference 4. (ie, ratio of whey protein to casein) in 2 mothers during lactation. Data from reference 4. NPN constitutes Ϸ20–25% of total nitrogen, and the use of the nitrogen content and a conversion factor will overestimate milk protein considerably. A more accurate approach is to determine A case could be made that biologically active peptides that are the total nitrogen and NPN contents, subtract the NPN value from formed during the digestion of several human milk proteins, such total nitrogen, and then multiply the value by the conventional as casein phosphopeptides, also represent indigestible protein and Kjeldahl factor of 6.25 (6). This slightly underestimates the total that they should not be included in the total protein content of amino acid equivalents because small peptides and free amino breast milk. However, no such peptides have been detected in the acids are included in the NPN fraction, but this amount is only a stool of breastfed infants, and a likely scenario is that they are few percent of the total. It is, of course, possible to determine the transiently formed during digestion in the upper gastrointestinal precise amino acid content and the true protein content ( amino tract. It is possible that they may be formed in the duodenum or nitrogen) by amino acid analysis, but this procedure is expensive upper jejunum to exert their physiologic activity locally, to sub- and time-consuming. True protein contents determined with the sequently be completely digested and absorbed in the lower use of the “corrected Kjeldahl” method and amino acid analysis jejunum and ileum. Further experimental evidence is needed to have been shown to agree closely (6). support this scenario. The true protein content of breast milk, determined as described above, is 14–16 g/L during early lactation, 8–10 g/L at 3–4 mo of lactation, and 7–8 g/L at 6 mo and later (1, 4). It has been argued ROLE OF HUMAN MILK PROTEINS IN NUTRIENT that these protein concentrations and, consequently, the corre- ABSORPTION sponding intakes do not accurately reflect the utilizable amounts It is well known that nutrients are utilized exceptionally well of amino acids provided to breastfed infants. This argument is from breast milk. Several factors likely contribute to this high based on the observation that intact breast-milk proteins can be degree of utilization, and some of these factors may be proteins found in the stool of breastfed infants; thus, they are incompletely present in human milk. There are proteins that bind essential nutri- digested and do not represent utilizable amino acids (7). It has ents, help keep them in solution, and facilitate their uptake by the therefore been suggested that such proteins [eg, lactoferrin and intestinal mucosa. Other proteins (protease inhibitors) may assist secretory immunoglobulin A (sIgA)] should be subtracted from in this process by limiting the activity of proteolytic enzymes, the protein concentration of breast milk to derive a true digestible thereby preserving the physiologic function of some relatively sta- protein content. However, it is not correct to assume that these ble binding proteins. Furthermore, some enzymes can affect the proteins are completely indigestible, even if they have properties digestion and utilization of macronutrients. that make them more resistant to proteolytic enzymes than are most other proteins. It is only a minor fraction that escapes diges- Activities related to digestive function tion; for example, it has been estimated that 6–10% of lactoferrin Bile salt–stimulated lipase is not digested by breastfed infants (7). The quantitatively most significant of the relatively indigestible human milk proteins are The presence of bile salt–stimulated lipase in human milk may lactoferrin and sIgA. The total concentration of these 2 proteins aid in the digestion of lipids in newborns, particularly in preterm in mature milk (> 30 d of lactation) is Ϸ2 g/L; assuming that infants, who have low lipase activity and poor lipid utilization 6–10% is undigested, there is a potential loss of Ϸ0.12–0.2 g/L (8, 9). It has been shown that the heating of breast milk, which (or Ϸ1.2–2.0% of total protein intake), which may be within the destroys the activity of bile salt–stimulated lipase, results in margin of error for the analysis used.
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