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Breastfeeding: Unraveling the Mysteries of Mother's Milk

, Georgetown University Medical Center

Medscape General Medicine. 1996;1(1)

Abstract and Introduction

Abstract

Most of the major progress in understanding the unique and complex features of human breast milk has emerged in
just the past 2 decades. Since the late 1970s, key research has examined such aspects as the composition of breast
milk, effects of maternal and environmental factors on human milk, and the effect of human milk on the infant, including
the protection against disease that breast milk can confer on the newborn. The composition of human breast milk
includes growth factors, hormones, enzymes, and other substances that are immune-protective and foster proper
growth and nutrition in the newborn. Research suggests that lactation is robust and that a mother's breast milk is
adequate in essential nutrients, even when her own nutrition is inadequate. Mature breast milk usually has constant
levels of about 7g/dL carbohydrate and about 0.9g/dL proteins. But the composition of fats essential for neonatal
growth, brain development, and retinal function varies according to a woman's intake, the length of gestation, and the
period of lactation. Vitamins and minerals also vary according to maternal intake. But even when these nutrients are
lower in breast milk than in formulas, their higher bioactivity and bioavailability more nearly meet the complete needs of
neonates than do even the best infant formulas. Also, in many instances human milk components compensate for
immature function, such as a neonate's inability to produce certain digestive enzymes, immunoglobulin A (IgA),
taurine, nucleotides, and long-chain polyunsaturated fatty acids.

Introduction

Even when a mother's own supply of nutrients and energy is limited, she still is able to produce breast milk of sufficient
quantity and quality to support the growth and health of her infant. This finding that "lactation is robust" is one of
several discoveries to emerge in recent years.[1] The quest to better understand the complex features of human breast
milk has been building in the past 2 decades, as evidenced by the growing number of international meetings, expert
work groups, and publications focusing on human breast milk. Since the late 1970s, key research has addressed such
topics as analyzing human milk,[2-4] identifying how maternal and environmental factors affect breast milk,[5] and
determining the effect of human milk on the infant,[6,7] including the protection against disease that breast milk can
confer on the newborn.[8]

Human milk, like the milk of many other mammals, is specifically adapted to the needs of the newborn. Before birth,
the mother transfers nutrients and bioactive components through the placenta[9]; after birth, these substances are
transferred through colostrum and milk. In contrast to infant formula, human milk offers the infant nutrients with high
bioavailability as well as a large number of bioactive components that confer immune and nonimmune protection
against pathogens in the infant's environment. Also, in many instances human milk components compensate for
immature function, such as a neonate's inability to produce certain digestive enzymes, immunoglobulin A (IgA),
taurine, nucleotides, and long-chain polyunsaturated fatty acids (LC-PUFA), among other substances. Because many
of these components remain intact during pasteurization, it is more advisable to feed pasteurized human donor milk to
infants whose mothers are unable to nurse than it is to substitute formula.[1] Its bioactive components make human
milk superior to even the best infant formulas.

Milk Volume and Composition

Volume. Milk volume is relatively constant irrespective of maternal nutritional status (Fig. 1). In general, healthy infants
consume an average of 750-800mL milk daily for the first 4-5 months after birth (range, 450 to 1200mL/day).[1,10,11]
Similar findings were reported from developing countries where maternal nutrition is sometimes subject to greater
seasonal variation and may be less adequate compared with industrial countries.[1,11] Increasing the intake of fluid
does not seem to affect milk volume.[10] Therefore, lactating women should maintain adequate fluid intake but should
not attempt to boost milk volume by consuming excess fluids.[1]

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Figure 1. In general, healthy infants consume 450 to 1200mL/day first 4-5 months after birth. Milk volume is
relatively constant irrespective of maternal nutritional status. Photo courtesy of Susanrachel Condon.

Major nutrients. Lactose, 5.5-6.0g/dL, is the most constant nutrient in human milk (Table I). Its concentration in breast
milk is not affected by maternal nutrition.

Proteins amount to about 0.9g/dL in mature milk.[12]Recent studies comparing the impact of nutrition on lactation in
industrialized and developing countries suggest that neither maternal diet nor body composition affects milk protein
level.[1] However, limited data from earlier studies seem to indicate that short-term, high-protein diets can increase the
protein and nonprotein nitrogen content of human milk,[13] while limiting maternal food intake can lead to lower milk
protein levels.[13-15]

The majority of milk proteins provide the newborn with immune and nonimmune protection from infection. These
proteins--immunoglobulins A, G, and M; lactoferrin; and lysozyme--have various functions in the newborn.[16] Early
studies suggested that the level of these protective proteins in milk is affected by maternal diet, but more recent
research suggests that immunoglobulins might be stable for a wide range of diets.[17-20]

Fat. While the amount and composition of carbohydrate and protein remain relatively constant in mature human milk,
the composition of fat is highly variable and is affected within hours and to a large extent by maternal nutrition intake.
[21] Gestation, lactation, parity, milk volume, caloric and carbohydrate intake, and weight changes are among the
maternal factors that can alter the fat content and composition of breast milk. Specifically, phospholipid and cholesterol
content are higher in colostrum preterm than term breast milk. Also, long chain polyunsaturated fatty acids (LC-PUFA)
are higher in preterm and transitional milk and remain high for the first 6 months in women who deliver preterm. In term
milk, on the other hand, LC-PUFA declines throughout the first 6 to 12 months of lactation. The endogenous synthesis
of fatty acids (FA) declines with parity, most notably after 10 births, but FAs (C6-C16) rise with a high-carbohydrate
diet. Palmitic acid (C16) content of breast milk increases in a low-calorie diet. Weight gain during pregnancy is
positively associated with higher milk fat content. During infant feedings, fore milk has less fat content than hind milk.
Also, the higher the volume of breast milk, the lower the milk fat concentration.[92] The lengths of both gestation and
lactation affect phospholipid and cholesterol, the lipids that constitute the milk fat globule membrane.[22] In the early
stage of lactation, because the milk fat globules are much smaller than in mature milk,[23,24] the total "membrane" lipid
level is higher in colostrum and transitional milk than in mature milk. The period of colostrum lasts less than 10 days,
but during this short time the higher lipid levels are beneficial in such processes as neonatal cell membrane production

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needed for growth, brain development, and bile salt synthesis. LC-PUFAs--C20:4n6 and C22:6n3, arachidonic, and
docosahexaenoic acids, respectively--are milk fats essential for neonatal growth, brain development, and retinal
function.[25,26] These fatty acids are stored in the fetus only in the last trimester of pregnancy; therefore, preterm
infants are born with low reserves of LC-PUFA, and their best source for these essential fatty acids is human milk. LC-
PUFA levels normally decrease in breast milk during lactation, but in women who have delivered infants before term,
the levels remain constant in preterm milk for at least 6 months[27]. Holman and colleagues[28] have reported that
levels of LC-PUFA often decline in pregnant and lactating women, suggesting that there is a preferential transfer of
these essential fatty acids from mother to fetus or to the newborn through milk, even at the cost of possible depletion
of maternal reserves. Depletion of maternal reserves might suggest the need for supplementation of pregnant and
lactating women with LC-PUFA.

Milk fat content changes dramatically during each feeding[29,30] and fat composition is markedly affected by the
maternal diet.[31] Some studies have shown that the mechanism for endogenous synthesis of fatty acids (ie, mainly
medium chain fatty acids) seems to become exhausted in women of very high parity[32]; that infants who receive milk
with low fat content (ie, less than 3.0 g/dl when the norm is 3.5 to 4.5 g/dl) tend to nurse more frequently and for longer
time periods, thereby causing an increase in milk volume[33]; and that there is a strong positive relationship between
weight gain during pregnancy and milk fat content.[34]

Vitamins and minerals. The vitamin content of human milk depends on the mother's vitamin status; when maternal
intake of specific vitamins is chronically low, these vitamins in turn are found in low levels in the milk. Vitamin
supplementation raises vitamin concentrations in milk. Water-soluble vitamins in milk are generally more responsive to
maternal dietary intake than fat-soluble ones.[1]

The relationship between maternal intake of vitamins and their concentration in milk varies according to the specific
vitamin. For example, excess vitamin C intake does not further increase the level in milk (above that associated with
adequate intake), whereas vitamin B6 concentrations in milk continue to rise with higher intakes. Folate levels in milk
remain normal even at the expense of maternal folate stores and do not decrease until the latter are depleted.[1] Based
on infant needs and the concentrations of fat-soluble vitamins in human milk, the Institute of Medicine (IOM) advises
that in the US all newborns receive 0.5-1.0mg vitamin K by injection or 1.0-2.0mg orally immediately after birth.[1,10]
Infants should receive 5.0-7.5ug vitamin D per day if exposure to sunlight seems inadequate.

The concentration of trace minerals (iron, copper, zinc, selenium) varies as a function of length of lactation.
Concentrations of iron[35,36] and fluoride[37] in milk seem to be independent of maternal nutrition. Concentrations of
manganese,[38] iodine,[39] and selenium[40] depend on maternal nutrition. Iodine is unique among trace elements in
that it is avidly accumulated by the mammary gland[1].

Because of the high bioavailability of iron in human milk, exclusively breast-fed infants do not need iron supplements
during the first 6 months of life. When supplementary foods are introduced (as recommended after 4-6 months of
exclusive breast-feeding), iron supplements should be added to the infant's nutrition[35, 36]. It is recommended that
breast-fed infants receive supplemental fluoride if the water supply in the area has only low levels (<0.3ppm).

It is important to assess not only the concentration of milk components but also the amount delivered to the infant.
Thus, while some milk components are present at a higher concentration in colostrum than in milk, one has to consider
the marked differences in volume: colostrum amounts to about 100mL/day, whereas average milk volumes are 750-
850mL/day.

Bioactivity of Human Milk

Breast milk provides not only essential nutrients but also a great number of other specific functions in the newborn. For
example, major nutrients, protein, carbohydrate, and fat, in addition to serving as building blocks for the infant's tissue,
carry out anti-infective as well as nutrient-enhancing functions, such as transporting essential elements and aiding
digestion. Furthermore, even when concentrations in human milk are markedly lower than in bovine milk or formula,
nutrients from human milk might have much greater bioavailability for the infant because of specific biologic factors,
such as the infant's receptor-mediated uptake of iron from human milk. Thus, in spite of a relatively low concentration
of some nutrients, human milk might be superior to other nutrient sources in providing these nutrients to the infant. The
apparently lower concentration of some nutrients in human milk such as vitamin D, pantothenic acid, and folate, might
be due to the fact that they are bound to other components or, lower concentrations may be due to shifts from the
aqueous phase to the fat phase of milk upon standing after the milk has been expressed from the breast (vitamin D).

Immune and Nonimmune Protecting Agents

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All proteins in human milk have bioactive functions in addition to providing amino acids for protein synthesis by the
newborn. Whey proteins, for example, have been reported to provide immune and nonimmune protection.[41,42]
Recently, casein has been shown to prevent the attachment of Helicobacter pylori to human gastric mucosa.[43]

Most proteins in human milk are heavily glycosylated[44] and are therefore resistant to proteolysis both after ingestion
by the infant[42,45] and after short-term storage (4-24 hours) at low to moderate ambient temperatures
(15deg.-25deg.C).[46,47]

Early in studies of human milk, researchers became aware that certain substances--most notably, IgA, lysozyme, and
lactoferrin--that are abundant in human milk (compared with bovine milk)[41] might protect the infant from infection.[47]
This observation has progressed within the last 2 decades to a fuller appreciation of several characteristics of breast
milk's protective features:

Immunoprotective substances act at mucosal sites.

Because of their resistance to digestive enzymes, protective factors are well adapted to persist in the hostile
environment of the gastrointestinal tract.

They kill certain bacterial pathogens synergistically.

Protection is achieved without triggering inflammatory reactions.

The daily production of many immunoprotective factors changes as lactation proceeds.

The secretion of many soluble defense agents by the mammary gland is inversely related to the capacity of the
recipient infant to produce them at mucosal sites.[41, 49-51]

The presence in milk of immunomodulators that fine-tune the interrelationships among the various protective agents
has recently been reported and is currently being investigated (Table II).[52] Secretory immunoglobulin A (sIgA),
dimeric IgA coupled to the secretory component, is the main immunoglobulin in human milk. IgG and IgM are also
present in milk, but at much lower concentrations. The changing concentration of these immunoglobulins in milk
provides an example of the interaction between milk components and the functional development of the infant: while
IgG and IgM rise rapidly after birth, the newborn maintains low levels of endogenous IgA during the first year of life. IgA
is produced in the mammary gland in B cells, which originate at maternal sites of high environmental pathogen
exposure (eg, the small intestine or respiratory tract), and therefore protects the infant against pathogens present in
the immediate environment.

Table III summarizes the enteric and respiratory pathogens against which the infant is protected by specific IgA
antibodies in human milk. IgA is resistant to proteolysis, acts at mucosal surfaces, and protects by noninflammatory
mechanisms; all of these properties enable efficient action in the infant.

Human milk lacks inflammatory mediators, and contains anti-inflammatory agents such as antiproteases, antioxidants,
and enzymes that degrade inflammatory mediators and modulators of leukocyte activation (Table IV).[49] Furthermore,
IgE (the principal immunoglobulin responsible for immediate hypersensitivity reactions), basophils, mast cells,
eosinophils (the principal effector cells in these reactions), and the mediators from these cells are absent in human
milk. Immune and nonimmune protecting agents are present in milk throughout lactation and some, such as lysozyme,
are present at higher concentrations during prolonged lactation than during the early stages. Therefore, although it is
strongly advocated that breast-fed infants receive food supplements after 4 to 6 months of exclusive breast-feeding, it
is advisable to breast-feed for longer periods in geographic areas where the environment may be contaminated with
pathogenic microorganisms, in order to provide the infant and toddler the benefits of milk-borne protective agents.

Studies also indicate that a glycoconjugate present in human milk, but absent in either human serum or bovine milk,
inhibits the binding of HIV envelope glycoprotein (gp120) to the CD4 receptor of T lymphocytes.[53,54]

In addition to soluble antigens and anti-infective agents, human milk contains leukocytes; the majority (90%) are
neutrophils and macrophages. Lymphocytes account for approximately 10%. The number and type of leukocytes
change with duration of lactation. Most of the lymphocytes in milk are T cells. The proportions of CD4 (helper) to CD8
(suppressor/cytotoxic) cells in human milk are similar to those in blood. Cytokines in human milk (eg, TNF-alpha and
IL-1-beta) have been shown to enhance the anti-infective function of milk leukocytes. Milk macrophages might
participate in the process of immunogenesis in the infant.

The immune and nonimmune protection provided by milk results in a lower incidence of necrotizing enterocolitis[55]
and other gastrointestinal and respiratory infections in breast-fed infants than in formula-fed infants[56]. The incidence

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of otitis media is also lower than in formula-fed infants. In addition to protection against some infectious diseases,
breast-fed infants might also be protected at later ages from diseases that are sequelae of infectious insults (eg,
insulin-dependent diabetes mellitus, lymphoma, and Crohn's disease). Immune factors provided by human milk that
compensate for their delayed production by the infant are summarized in Table V.

Oligosaccharides (which amount to 1.0-1.5g/100mL of human milk),[53] glycoconjugates, mucins, and glycolipids act
as receptor analogs and thereby inhibit the binding of enteric and respiratory microorganisms and their toxins.[57] In
addition, the hydrolysis of milk triglycerides (the major component of milk fat) during digestion in the stomach and
intestine[59] produces free fatty acids and monoglycerides that have been shown to have antiviral, antiprotozoan, and
possibly also antibacterial activity.[60]

Growth Factors and Hormones

The presence of growth factors and hormones in milk and their function has been known for some time (Table VI, VII).
[61-64] Interestingly, the concentration of many growth factors and hormones is higher in a woman's milk than in her
plasma. The milk hormones, however, often differ in structure from their maternal serum counterparts, suggesting
modification (often post-translational processing such as glycosylation) within the mammary gland. These glycosylated
forms often are difficult to detect by standard RIA techniques and have to be quantitated by specific bioassays.[62] The
stronger glycosylation protects these bioactive components during passage through the gastrointestinal tract and
probably enables the newborn to absorb growth factors and hormones from mother's milk.

It appears that variants of prolactin are present in the circulation of the newborn and that the prolactin acquired from
breast milk, and not endogenous prolactin secreted by the newborn's pituitary gland, is essential for the normal
development of the neuroendocrine regulation of prolactin in the newborn.[62,65]

Many hormones act in the newborn. While the exact mechanisms of uptake from milk and their mode and site of action
in the newborn are known for some, further study is needed to identify these mechanisms for most hormones. Agents
in milk seem to stabilize hormones in the gastrointestinal tract of the newborn.

In addition to prolactin, other hormones such as progesterone are present in different form in breast milk than in
maternal serum. Transfer of these hormones from milk to infant was documented in some studies directly; in other
studies, this transfer is inferred from the documentation of higher serum level of the hormone--for example, thyrotropin
releasing hormone (TRH) and somatostatin--in breast-fed than in formula-fed newborns[61]. The milk hormones may
also be modified as they pass through the gastrointestinal tract and prior to release into the newborn's blood.

Enzymes

Human milk contains a great number of enzymes, many of which have specific transport functions (Table VIII). For
instance, xanthine oxidase acts as a carrier of iron[65] and glutathione peroxidase carries selenium.[66] Although
proteases are present in human milk, it is not known how much of that activity is expressed because of the
antiprotease activity of human milk itself.[66] One can postulate that antiproteases might protect the mammary gland
from local proteolysis (caused by leukocytic or lysosomal proteases) and might prevent the proteolytic breakdown of
milk proteins, many of which have to reach the infant intact (eg, immunoglobulins, digestive enzymes). The antitryptic
and antichymotryptic activity of human milk might prevent the absorption of endogenous and bacterial proteases in
infants and thereby contribute to the passive protection of extraintestinal organs such as the liver.[67] The high activity
of antiproteases in colostrum coincides with the period of greatest transfer of nonimmunoglobulin protein from the
intestine to the systemic circulation of the newborn.

The digestive enzymes in milk (amylase and digestive lipase) act in the newborn to compensate for immature
pancreatic function. These enzymes are remarkably stable for years in milk stored at low temperature (-20deg.C or
-70deg.C). Moreover, activity is unchanged after storage for 24 hours at 38deg.C. The stability of enzymes and of
other proteins in milk might be due to the antiprotease activity of milk. Furthermore, many enzymes are stable in the
gastrointestinal tract of the newborn.

Amylase,[68] an enzyme identified in milk more than a century ago,[69] may be more important to the infant after
initiation of starch supplements[70] or when formula that contains oligosaccharides hydrolyzed by amylase is fed to
partially breast-fed infants. Amylase activity in the duodenum of the newborn is only 0.2% to 0.5% of the adult level. At
the time of supplementation (after 4 to 6 months of exclusive breast-feeding), the infant is still deficient in
endogenously produced amylase.[71] The latter secreted from salivary glands and pancreas does not reach adequate
levels until 2 years after birth. Other infants and toddlers who might benefit from milk amylase are those with

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pancreatic insufficiency caused by diseases such as cystic fibrosis[72] or malnutrition.[73-75] Because of the potential of
bile salt-dependent lipase in milk[76] to compensate for the low pancreatic lipase in the newborn,[77,78] this enzyme
has received great attention in the past decade.[44,66] The characteristics of the digestive enzymes of human milk are
summarized in Table IX.

Other Essential Components in Human Milk

Several milk components are essential because they have to be provided to the newborn, while older children and
adults have the ability to synthesize these components. Among these are carnitine,[79] taurine,[80] and LC-PUFAs[26]
that are produced by elongation and desaturation of the precursor fatty acids, linoleic (C 18:2, n-6), and linolenic
(C18:3, n-3) acids, and nucleotides[81] that have to be provided to the intestine and lymphatic tissues because they
cannot be synthesized either from the diet or de novo in other organs.[82] The need for these essential components
might be even greater in premature infants who are born before fetal intrauterine reserves have been laid down.

The breakdown of milk casein produces beta-casomorphins; these short peptides have been shown to affect a variety
of physiologic systems.[83] Because they are opioid agonists, these peptides also have behavioral effects, such as
lowering response to pain and elevating mood, that can affect the nursing mother or the newborn. Most of the effects
of the beta-casomorphins have been studied in such animals as rats, pigs, and chickens[83].

Human Milk After Preterm Delivery

The milk produced by women who deliver prematurely differs from that produced after a full-term pregnancy.
Specifically, during the first month after parturition, preterm milk maintains a composition similar to that of colostrum.
Colostrum, secreted during the first few days after parturition, contains higher concentrations of protein (including
higher levels of protective proteins such as secretory IgA, lactoferrin, and lysozyme), sodium, and chloride, and
contains lower amounts of potassium, carbohydrate, fat, and certain vitamins. While the transition from colostrum to
mature milk is rapid after full-term pregnancy, it proceeds much more slowly after premature delivery.[84]

Some of the nutritional needs of preterm infants, therefore, cannot be met by feeding the preemie breast milk only.
While the mother's own preterm milk is preferable to donor-banked full-term milk, either diet has to be supplemented
with protein, calcium, and phosphorus in the preterm infant.[85] However, given the many benefits to the preterm infant
that accrue from the mother's own milk, efforts should be made to encourage mothers of preterm infants to breast-
feed, even if during the early stages this might necessitate milk pumping while the infant is hospitalized or is too
immature to nurse.

Long-Term Effects of Breast-feeding

Human milk not only is beneficial during infancy,[1,2,7,8] but it also may protect the child from chronic diseases that
develop at later ages, such as Crohn's,[86] diabetes mellitus,[87] and lymphomas.[88] Also, cognitive development,
assessed at 7.5-8.0 years of age, seems to be affected by early diet in the preterm infant. A significantly higher score
on the Wechsler Intelligence Scales for Children-Revised (WISC-R) was found in children fed expressed human milk
than in those fed formula in early infancy.[89,90] Similar findings have been reported for full-term infants.[91]

Conclusion: Continuing the Progress in Understanding and Promoting Breast-feeding

Given the short-term and long-term benefits of breast-feeding, many working women continue to breast-feed after
returning to work. Collection and proper storage of milk in the workplace might not always be easy, because it may be
difficult to find a quiet, isolated place where the mother can pump milk, or a refrigerator for milk storage. However, one
study showed that milk can be safely stored for up to 24 hours at 60deg.F,[47] a temperature that can be maintained in
a styrofoam box with a frozen ice pack. Efforts should be made to make the workplace an easier environment in which
women who choose to breast-feed can do so.

We have just begun to assess the many components in human milk and their interaction with the infant. Much work
lies ahead to understand in depth the immediate and long-term effects of feeding mother's milk to newborns. As
researchers continue to discover the unique features of breast milk, clinicians need to encourage the practice for the
sake of the benefits breast-feeding can bring to both mothers and infants.

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Tables

Table I. Concentrations of Nutrients in Mature Human Milk

Major nutrients g/liter

Carbohydrate 72.0±2.5
Protein 10.5±2.0
Fat 39.0±4.0
Macronutrients
Minerals mg/liter
Calcium 280±26
Chloride 420±60
Magnesium 35±2
Phosphorus 140±22
Potassium 525±35
Trace Elements ug/liter
Chromium 50±5
Copper 250±30
Fluoride 16±5
Iodine 110±40
Iron 300±100
Manganese 6±2
Molybdenum NR
Selenium 20±5
Zinc 1200±200
Vitamins
Fat-soluble mg/liter
Vitamin A, RE* 670±200 (2230 IU)
Vitamin D 0.55±0.10
Vitamin E 2300±1000
Vitamin K 2.1±0.1
Water-soluble mg/liter
Vitamin B6 93,000±8,000
Vitamin B12 0.97
Biotin 4±1
Vitamin C 40,000±10,000
Folate 85±37

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Niacin 1500±200
Pantothenic acid 1800±200
Riboflavin 350±25
Thiamin 210±35
Reprinted from Hamosh et al: Nutrition During Lactation, (1991, p 116), Copyright (c) 1991, National Academy
Press.Data (means ± SD); IU = international units; NR = not reported; RE = retinol equivalents.

Table II. Cytokines in Human Milk: Mean Concentrations and Potential Functions*

Cytokines Possible Functions Concentrations

IL-1b Activates T cells ~ 1130pg/mL
IL-6 Enhances IgA production ~ 151pg/mL
IL-8 Chemotaxin for neutrophils/T cells ~ 3500pg/mL
IL-10 Decreased inflammatory cytokine synthesis ~ 3500pg/mL
TNF-a Increased secretory component production ~ 620pg/mL
TGF-b Enhances Ig isotype switching to IgA+ B cells ~ 130pg/mL
M-CSF Induce proliferation and differentiation of macrophages ~ 2000-9000 U/mL
*Milk collected during the first several days of lactation. Data are mean values.
From Goldman AS, et al. [42]

Table III. Enteric and Respiratory Pathogens Commonly Targeted By Secretory IgA Antibodies Found in
Human Milk

Enteric Pathogens Respiratory Pathogens

* Bacteria, Toxins, Virulence Factors * Bacteria
Clostridium difficile Haemophilus influenzae
Escherichia coli Streptococcus pneumoniae
Salmonella spp Klebsiella pneumoniae
Shigella spp
Vibrio cholerae * Viruses
Influenza viruses
* Parasites Respiratory syncytial virus
Giardia lamblia
* Fungi
* Viruses Candida albicans
Polioviruses
Rotaviruses * Food Proteins
Cow's milk
Soy
From Goldman AS, Goldblum RM. Immunologic systems in human milk: Characteristics and effects, in Lebenthal
E (ed): Textbook of Gastroenterology and Nutrition in Infancy, ed 2. New York, Raven Press, 1989, pp 135-142.

Table IV. Anti-Inflammatory Components in Human Milk

Component Enzymes Function

Catalase Degrades hydrogen peroxide
Histaminase Degrades histamine
Arysulfatase Degrades leucotrienes
Antioxidants Scavengers of oxygen radicals

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a-Tocopherol
Cysteine
Ascorbic acid
Antiproteases Neutralize enzymes that act in inflammation
a -1-antitrypsin
a -1-antichymotrypsin
Prostaglandins Cytoprotective
PG-E2
PG-F2
Reprinted from Acta Paediatr Scand (1986; 689), Copyright (c) 1986, Scandinavian University Press.

Table V. Immune Factors in Human Milk that Compensate for Delayed Production in Infants

Immune Factors in Human Milk When Immune Factors Mature in the Infant
Secretory IgA (sIgA) ~ 4-12 months
Full antibody repertoire ~ 24 months
Lysozyme ~ 1-2 years
Lactoferrin ?
Interleukin-6 ?
PAF-acetylhydrolase ?
Memory T cells 2 years
Reprinted from Pediatr Infect Dis J (1993; 12:664-672), Copyright (c) 1993, Williams and Wilkins.

Table VI. Growth Factors in Human Colostrum and Milk

Growth Factor Colostrum Milk

EGF* 6-73 nM 3-19 nM
NGF Not quantified
Insulin* 21.5±5mg/L 2.6±0.3mg/L
IGF-I 10.9±5.3mg/L 7.1-19.1mg/L
IGF-II NR 2.7±0.7mg/L
Relaxin 327±110mg/L 509±5.3ng/L
TGF-a 2.2-7.2mg/L 0-8.4mg/L
* EGF concentration higher in preterm colostrum and milk, insulin concentration lower in preterm colostrum and
milk than in term milk. From Donovan et al. [64]

Table VII. Function of Milk-Growth Factors and Hormones in the Mammary Gland and Newborn

Growth Maternal Mammary Gland Newborn

Factor/Hormone
PRL Maintenance of lactation Neuroendocrine and immune system
Corticosterone Synthetic capacity (enzymes, specific Response to stress in the adult
proteins, etc.)
Insulin Growth via IGF-II or IGF-I Neonatal glycemia
IGFs Growth and (?) differentiation of gland GI growth, affect IGF receptors in intestine (?)

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systemic growth effects

Relaxin Growth and differentiation
EGF, TGF-a Growth GI growth, gut closure, eye opening
TGF-b Inhibits growth Inhibits enterocyte growth in ovarian GnRH
receptors
GnRH (?) GH secretion
GRH (?) GH secretion
TRH (?) TSH secretion
PTHrP (?) Ca/P/Mg in milk
Salmon calcitonin-like PRL inhibiting factor
peptide
Erythropoietin Stimulates erythropoiesis
Prostaglandins Cytoprotection for intestine
EGF: epidermal growth factor; IGF: insulin like growth factor; PRL: prolactin.
From Grosvenor et al. [62]

Table VIII. Functions of Enzymes in Human Milk

Function Enzyme(s) Process(s)

Biosynthesis of milk Phosphoglucomutase
components in the mammary
gland Lactose synthetase
Fatty acid synthetase
Lipoprotein lipase
Digestive function in the infant Amylase
Lipase (bile salt-dependent)
Proteases*
Transport in the infant Xanthine oxidase
Glutathione peroxidase
Alkaline phosphatase
Preservation of milk Antiproteases
components
Sulfhydryl oxidase
Anti-infective agents Lysozyme
Peroxidase
Lipases (lipoprotein lipase, bile Release of free fatty acids that have
salt-dependent lipase)
Protection against enterocolitis PAF-AH
Synthesis of lactose
Synthesis of lactose
Synthesis of medium-chain fatty acids
Uptake of circulating triglyceride fatty acids
Hydrolysis of polysaccharides
Hydrolysis of triglycerides
Proteolysis (not verified)
Carrier of iron, molybdenum
Carrier of selenium
Carrier of zinc, magnesium
Protection of bioactive proteins (ie, enzymes and
immunoglobulins)
Maintenance of structure and function of proteins
containingS-S bonds
Bactericidal
Bactericidal
antibacterial, antiviral,and antiprotozoan actions
Hydrolysis of platelet necrotizing activity factor

*It is not known whether the proteolytic enzymes of milk are active because of possible interaction with milk
antiproteases. PAF-AH = Platelet activity factor acetyl hydrolase.
From Hamosh.[66]

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Table IX. Characteristics of Milk Enzymes Active in Infant Digestion Enzyme

Characteristic Maternal factors Amylase Bile salt-dependent lipase

High parity (>10) Low activity
Malnutrition ? Decrease in activity
Diurnal and within feed activity Constant Constant
Pattern of secretion
Prepartum ? Present
Colostrum Colostrum greater than milk Colostrum lower than milk
Milk after preterm (PT) and term (T) Equal activity PT and T Equal activity PT and T
delivery
Weaning ? Activity constant independent of milk
volume
Distribution in milk Aqueous phase Aqueous phase
Effect of milk storage Temperature
Cold: -20deg.C to -70deg.C Stable Stable
Warm: +15deg.C to +38deg.C Stable (at least 24 hrs)
Stable (at least 24 hrs)
Effect of pH
Low pH (pH>3.0) (passage through Stable Stable
stomach)
pH optimum 6.5-7.5 7.4-8.5
Enzyme character Identical to salivary amylase Identical to pancreatic carboxyl ester
isozyme lipase
Evidence of activity in infant's intestine Yes Yes
Presence in milk of other species ? Yes, in primates and carnivores
From Hamosh. [66]
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