Perfect Evolutionary Food:

Breast MilkGeza Bruckner, PhD

Professor Clinical Nutrition

Division of Clinical Nutrition

Graduate Center for Nutritional Sciences

Objectives

• To introduce the audience to some of the myriad of bioactive compounds in human milk

• To differentiate between the nutrient content of human versus cows milk and infant formulas

• To elucidate the role of n3 fatty acids found in breast milk

• To illuminate the importance of oligosaccharides in breast milk

• To impart knowledge to the audience regarding breast milk’s composition and the bio-functionality of it’s constituents

Human milk, being the sole source of early

infant nourishment, has evolved as a result of

200 million years of Darwinian pressure on

mammalian lactation to become the perfect

species specific

neonatal nutrient.

Human milk components while nourishing

growth of the infant also provide a myriad of

bioactive compounds that modulate the immune

system, cognitive development, protection from

toxins and pathogenic diseases, and remarkably

the establishment of the intestinal microbiota.

Benefits of Breast Milk

• The most important short-term immunological benefit of breast-feeding is the protection against infectious diseases

• Another consistent findings of breast-feeding is a positive effect on later intelligence tests with a few test points advantage for breast-fed infants

– Plausible explanations include the LCPUFA content of human milk

– Stimulation and reinforcement of beneficial maternal behaviors during breast-feeding.

J. Nutr. 137: 503S–510S, 2007

Benefits of Breast Milk

• There is also some evidence of

– lower prevalence of:

• inflammatory bowel diseases,

• childhood cancers, and

• type I diabetes

– small protective effect for developing overweight and obesity

– Blood pressure and blood cholesterol seem to be slightly lower

– Slightly taller as adults

J. Nutr. 137: 503S–510S, 2007.

Antibodies and Other Defense Agents

in Human Milk• sIgA1 (polymeric IGA) – protective against E. coli, S. pneumoniae, influenza

viruses, etc.

• Leukocytes

• – B lymphocytes

• – Macrophages

• – Neutrophil

• – T lymphocytes*

• Oligosaccharides - prevent attachment of H. influenzae and S.pneumoniae to the respiratory epithelium - N-acetyl-glucosamine

• Bifidus factor - specifically enhances the growth of bifidobacteria in intestines of neonates - N-acetyl-glucosamine

• Lysozyme - lyses mostly gram-positive and few gram-negative bacteria

• Lactoferrin - bactericidal, antiviral, anti-inflammatory and modulates cytokine function

• Interferon-γ * - activation of intestinal T lymphocytes to enhance mucosal immunity

• Nucleotides* - enhance intestinal repair and potentiate the immune response to certain vaccines

• Cytokines*

*Factors that potentially may impart an imprint on the child’s own immune system.

Microbial phagocytosis, production of

lymphokines and cytokines, interaction and

enhancement with other protective agents

Benefits of Breast Milk

• Some of the effects of breast-feeding on the child’s

risk of acquiring infectious diseases continue after

breastfeeding is terminated.

– Protection against

• Haemophilus influenzae type B may last for 10 y

• respiratory tract infections for 7 y

• against otitis media for 3 y and

• against diarrhea for 2 y, accompanied by a reduced rate of hospital

admission

Int J Epidemiol. 1997;26:443–50

Int J Epidemiol. 1999;28:152–6

BMJ. 1998;316:21–5.

BMJ. 1990;300:11–6.

Milk Adapting to Need

• Human breast milk changes over the period of a few months. These changes in composition parallel the babies nutrient needs.

• Colostrum (late pregnancy, first week after child birth)

– Three times as much protein as mature milk.

– Low in fat and sugar

– Acts as a natural laxative helping the

– baby pass merconium.

– More antibodies

Milk Adapting to Need

• Colostrum also contains numerous growth factors, such as:

– insulin-like growth factors I, and II,

– transforming growth factors alpha, beta 1 and beta 2,

– fibroblast growth factors,

– epidermal growth factor,

– granulocyte-macrophage-stimulating growth factor

– platelet-derived growth factor,

– vascular endothelial growth factor,

– colony-stimulating factor-1

Milk Adapting to Need

• Transitional Milk is the milk made after

colostrum and before mature milk

(sometime between day 6 and day 14 after

birth).

– Its composition is somewhere between

that of colostrum and mature milk.

Mature Milk

Milk Adapting to NeedHuman Foremilk compared to Hind-milk

Milk/Formula Macro-Nutrient Comparisons

Nutrient/

100 gram

Breast

Milk

Cow

Whole

Milk

Formula

Pedisure

Formula

EnfamilFormula

Similac

Energy

kcal

70 71 99 71 78

Protein

gram

1.03 3.15

~3X

2.86

~2.5X

2.00

~2X

2.12

~2X

Lipid

gram

4.38 3.25

~3/4

2.86

~1/2

2.00

~1/2

2.12

~1/2

Sugars

gram

6.89 5.26

~3/4

10.50

~1.5X

7.40 8.20

Milk/Formula Nutrient ComparisonsNutrient/

100 gram

Breast

Milk

Cow

Whole

Milk

Formula

Pedisure

Formula

EnfamilFormula

Similac

Ca

mg

32 113

~4X

93

~3X

86

~3X

163

~5X

Fe

mg

.03 .03 1.34

~44X

1.28

~44X

.29

~9X

Mg

mg

3.0 10.0

~3X

19.0

~6X

6.0

~2X

9.0

~3X

P

mg

14.0 84.0

~6X

76.0

~5X

47.0

~3X

91.0

~6.5

K

mg

51.0 132.0

~3X

125.0

~2.5X

75.0

~1.5X

101.0

~2X

Na

mg

17.0 43.0

~2.5X

36.0

~2X

6.0

~1/3

34.0

~2X

Inadequacy of Cows Milk

• Whole cow's milk does not contain sufficient vitamin E, iron, or essential fatty acids, which can make infants fed on cow's milk anemic.

• Whole cow's milk also contains excessive amounts of protein, sodium, and potassium which may put a strain on an infant's immature kidneys.

• The proteins and fats in whole cow's milk are more difficult for an infant to digest and absorb than the ones in breast milk

• Evaporated milk may be easier to digest due to the processing of the protein but is still nutritionally inadequate.

• A significant minority of infants are allergic to one or more of the constituents of cow's milk, most often the cow's milk protein.

• These problems can also affect infant formulas derived from cow's milk.

Breastfeeding also provides health

benefits for the mother

• It assists the uterus in returning to its pre-

pregnancy size and reduces post-partum

bleeding

• Assists the mother in returning to her pre-

pregnancy weight.

• Reduces the risk of breast cancer later in life

n3 Fatty Acids and Breast Milk

• Why are n3 fatty acids important to the developing

fetus and the neonate?

– Needed for Brain Development

• Brain cortex in infants contains 8.5 ± 1.2 DHA in Breast Feed

infants versus 7.5 ± 0.8 DHA in Formula Fed (wt%)

• Retina contains ~ 12% DHA

• During the third trimester, approximately 50 to 60 mg/day of

maternal DHA stores are transferred to the fetus via the placenta

Am J Clin Nutr l994;60:l89-94.J Am Diet Assoc. 2009;109:668-679.

H3C COOH

C18:3 w-3

w-3 family

a-LinolenicFlaxseed Oil

Canola Oil

Soybean Oil

COOH

C20:5 w-3 Eicosapentaenoic

EPA

H3C

COOH

C22:6 w-3 Docosahexaenoic

DHA

H3C

Essential Fatty Acid Families

Oily Fish

Fish Oil Capsules

H3C

H3C

COOH

COOH

w-6 family

C20:4 w-6

C18:2 w-6 Linoleic

Arachidonic

Eicosanoids

Thrombotic

Inflammatory

Corn Oil

Safflower Oil

Sunflower Oil

Eicosanoids

Less thrombotic Less inflammatory

Meat, Eggs,

Brains

Milk fatty acid composition in first month of lactation (% wt/wt)

Selected

Fatty Acid

Colostrum Transitional

Milk

Mature Milk Formulas

Average 10

18:2n6 LA 16.10 15.74 16.59 15.0

20:4n6 AA 0.74 0.67 0.53 0 to 0.22

22:4n6 0.44 0.23 0.15 ND

Total n6 18.89 17.79 18.33 15.1

18:3n3 ALA 0.41 0.58 0.75 2.0

20:5n3 EPA 0.19 0.11 0.10 0 to 0.04

22:5n3 0.35 0.23 0.15 ND

22:6n3 DHA 0.56 0.50 0.29 0 to 0.28

Total n3 2.10 1.80 1.50 2.3

SFA total 44.66 45.05 45.49 43.00

MUFA 42.29 38.59 39.63 40.00

PUFA 20.34 19.26 19.71 15.00

EJCN December 2002, Volume 56, Number 12, Pages 1242-1254

n6 and n3 PUFA Glycerol Position

SN2

Milk Fatty Acids in the Sn2 Position %wt/wt

FA C TM MM F

20:4n6 1.16 0.88 0.67 ND

20:5n3 0.33 0.28 0.27 ND

22:6n3 0.93 0.81 0.64 ND

EJCN December 2002, Volume 56, Number 12, Pages 1242-1254

Summation of Studies on n3 and Neonatal Development

Breast Milk vs Formula Fed

• Most studies show improved cognitive scores

• Most studies show improved vision

! Note: improvement in cognition and vision was negated by

alcohol or marijuana use by the mother

Food and Nutrition Bulletin

Volume 17, Number 4, December 1996

Recent Study: Effect of DHA Supplementation During

Pregnancy on Neurodevelopment of Young Children

• Key Points

– STUDY - At 18 months detected no brain development benefits in those born to mothers who took 800mg of omega-3 DHA daily from gestation week 21 to birth.

– The brain function test used cannot predict the mental advantages seen at four years or later as found positive in other clinical trials

– The wisdom of higher maternal (and infant) fish and DHA consumption is supported by other clinical evidence and by reams of mutually reinforcing cell, animal, and population research.

– Average American women and children do not get the recommended amounts of omega-3s.

– Higher maternal fish intake may be a better fetal brain-booster, compared with taking omega-3 fish oil supplements during pregnancy.

– Study did not compare whether infants were breast fed or formula

• Perhaps DHA in Milk is more important to improve cognition than in utero

JAMA. 2010;304(15):1675-1683

Recommendations: Infants & Children• The American Academy

of Pediatrics recommends that infant milk formula should provide at least 2.7% of total kilocalories in the form of linoleic acid.

• Of note, human milk provides 3.5% to as high as 12% of total kilocalories in the form of linoleic aciddepending on the fat composition of the maternal diet.

AI for Infants and Children0-6 mos 0.5 g/day of n-3 PUFA

7-12 mos 0.5 g/day of n-3 PUFA

1-3 yrs 0.7 g/day of a-linolenic acid

4-8 yrs 0.9 g/day of a -linolenic acid

Boys

9-13 yrs 1.2 g/day of a -linolenic acid

14-18 yrs 1.6 g/day o a-linolenic acid

Girls

9-13 yrs 1.0 g/day of a -linolenic acid

14-18 yrs 1.1 g/day of a -linolenic acid

Food and Nutrition Board, Institute of Medicine (FNBIOM,2001)

Recommendations During Pregnancy

• Eat up to 12 ounces of fish or shellfish (2 average meals) a week, including shrimp, canned light tuna, salmon, trout, catfish (found consistently low in mercury)

• Limit albacore tuna to 6 oz per week.

• Do not eat shark, swordfish, king mackerel, or tilefish because they contain high levels of mercury.

• If supplementing with fish oil capsule 100 to 200 mg EPA & DHA/day (most fish oil capsules are low in mercury and other harmful contaminants)

Oligosaccharides

• Quantitatively, oligosaccharides are the third largest solute in human milk after lactose (70g/l) and fat (40g/l). Mature milk contains over 15 g human milk oligosaccharides/l compared with only about 9 g protein/l

• Function has only recently been investigated.

• HMOs are

• Composed of both neutral and anionic species with building blocks of five monosaccharides: D-glucose, D-galactose, N-acetylglucos-amine, L-fucose, and N-acetylneuraminic acid

Oligosaccharides

• One of the most remarkable functions of breast milk

is to support the selective colonization and support of

a beneficial gut microflora.

• There are over 200 different human milk

oligosaccharide (HMO) structures that differ in their

size, charge, and sequence

• A direct mechanistic link has been demonstrated

between specific HMO structures and bifidobacterial

growth

Oligosaccharides – How do they Work?

• Various oligosaccharides in milk are believed to inhibit the binding of pathogenic bacteria and toxins, presumably by acting as decoys and binding to the bacterial surface, thus inhibiting their ability to bind to target oligosaccharides on the surface of epithelial cells

• Only Bifidobacterium and Bacteriodes species are able to consume HMOs as a sole carbon source and achieve high cell densities

• Bifidobacteria constitute >80% of the colonic microbiota in breast fed infants which are able to prevent or alleviate infectious diarrhoea through their effects on the immune system and resistance to colonization by pathogens

Conclusion: Breast is Best

http://www.heelpress.com/piece/image/1574/display/Breast_Feeding.jpg

Appendix:

Bioactive Factors in Human Milk

• Table 1. Multiple Functions of the Major Nutrients of Human Milk in the Infant• ______________________________________________________________________________________

____________________

• Nutrients Amount Function Protein mg/dL

• sIgA 50-100 Immune protection

• IgM 2 Immune protection

• IgG 1 Immune protection

• Lactoferrin 100-300 Anti-infective, iron carrier

• Lysozyme 5-25 Anti-infective

• α Lactalbumin 200-300 Ion carrier (Ca++), part of lactose synthase

• Casein 200-300 Ion carrier, inhibits microbial adhesion to mucosal membranes

• Carbohydrate g/L

• Lactose 6.5-7.3 Energy source

• Oligosaccharides 1.0-1.5 Microbial ligands

• Glycoconjugates Microbial and viral ligands

• Fat g/L

• Triglyceride 3.0-4.5 Energy source

• LC-PUFA* Essential for brain and retinal development and for infant growth

• FFA** Anti-infective

• __________________________________________________________________________________________________________

• * LC-PUFA: long chain polyunsaturated fatty acids

• ** FFA: free fatty acids, produced from triglycerides during fat digestion in the stomach and intestine

•BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D.

Professor of Pediatrics, Department of Pediatrics

Georgetown University Medical Center Washington, D.C. 20007-2197

Table 2. Protective Components in Human Milk__________________________________________________________________________________________________________

Immune protection Function

pIgA, IgG, M, D, E Specific antigen targeted anti-infective activity

Nonspecific protection Antibacterial, antiviral and antimicrobial-toxin enhancing newborn’s immune system maturation

Major nutrients (See Tables 1, 3 and 5)

Minor nutrients

Nucleotides Enhance: T cell maturation NK cell activity, antibody response to certain vaccines,

intestinal maturation and repair after diarrhea

Vitamins

A (b-carotene) anti-inflammatory (scavenging of oxygen radicals)

C (ascorbic acid) anti-inflammatory (scavenging of oxygen radicals)

E (α-tocopherol) anti-inflammatory (scavenging of oxygen radicals)

Enzymes

Bile salt dependent lipase production of FFA with antiprotozoan and antibacterial activity

Catalase anti-inflammatory (degrades H2O2)

Glutathione peroxidase anti-inflammatory (prevents lipid peroxidation)

PAF - acetylhydrolase protects against necrotizing enterocolitis (hydrolysis of PAF)

Hormones

Prolactin enhances the development of B and T lymphocytes, differentiation of intestinal

lymphoid tissue

Cortisol, thyroxine, promote maturation of the newborn’s intestine and insulin and growth factors development of

intestinal host-defense mechanism

Cells

Macrophages, PMNs Microbial phagocytosis, production of lymphokines and cytokines, interaction and enhancement with

other protective agents

Cytokines Modulate functions and maturation of the immune system

__________________________________________________________________________________________________________

PAF: platelet activating factor; PMN: polymorphonuclear

BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D.

Professor of Pediatrics, Department of Pediatrics

Georgetown University Medical Center Washington, D.C. 20007-2197

Table 3. Protective Function of Human Milk Protein______________________________________________________________________________

____________________________Protein Protective Function

Lactoferrin Iron chelation: bacteriostatic for siderophilic bacteria and fungi

(500-600 mg/dL Lactoferricin, 18 amino acid loop has broad spectrum

colostrum, 150 antimicrobial action

mg/dL in mature Antiviral activity (HIV, CMV, HSV) probably by interfering

with milk) the stage of virus adsorption and/or penetration

Immunomodulating activity: reduced release of IL-1, -2 and -6

and TFN-a from monocytes and of PgE2 from macrophages;

activation of NK cells, effect on complement activation and

coagulation Antiadhesive for E. coli and antiinvasive for S. flexneri

Antiadhesive for E. coli and antiinvasive for S. flexneri

Affects neonatal intestinal growth and recovery from injury,

thereby reducing intestinal infection

Lysozyme Bacterial lysis: hydrolysis of b1-4 link between N-acetyl-

5-25 mg/dL glucosamine and N-acetylmuramic acid in bacterial walls

increases with Immunomodulating activity: muramyl dipeptide enhances IgA prolonged lactation

production, macrophage activation

Binding to bacterial lipopolysaccharides: reduces endotoxic effect

k-casein Antiadhesive: Inhibits binding of H. pylori to human gastric

< 100 mg/dL mucosa and S. pneumoniae and H. influenzae to human respiratory

tract epithelial cells

Casein macropeptide is a strong growth promoting factor for B.

bifidum

____________________________________________________________________________________________________

______

HIV: human deficiency virus, CMV: cytomegalovirus, HSV: herpes symplex virus

BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D. Professor of Pediatrics, Department of Pediatrics

Georgetown University Medical Center Washington, D.C. 20007-2197

Table 4. Protective Functions of Oligoconjugates in Human Milk______________________________________________________________________________

____________________________

Structure Distribution in Milk Function

Oligosaccharides skim milk Protect against heat stable E. coli enterotoxin,

attachment of H. influenzae and S. pneumoniae

to respiratory epithelium, V. cholerae

hemagglutinin activity

Glycoproteins MFGM/skim milk Prevent binding of V. cholerae El Tor

Mucin MFGM Prevents binding of S. fimbriated E.

coli

Lactadherin MFGM/skim milk Prevents binding of Rotavirus

Gangliosides MFGM Receptor analogs for heat labile toxins of V.

cholerae and E. coli

Glycosaminoglycan MFGM Inhibits binding of HIV gp 120 to CD4

receptor

______________________________________________________________________________

____________________________

MFGM: milk fat globule membrane. Most of the listed activities are based on in vitro studies,

however, lactadherin prevents rotavirus-caused diarrhea in mice and human infants.

BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D. Professor of

Pediatrics, Department of Pediatrics

Georgetown University Medical Center Washington, D.C. 20007-2197

Table 5. Protective Functions of Human Milk Lipids______________________________________________________________________________

____________________________

Structural determinants FFA and MG. Most active: Lauric acid (C12:0) and

of anti-infective activity linoleic acid (C18:2).

Role of digestion Milk TG (98% of milk fat) have to be hydrolyzed in the

stomach* and intestine** to FFA and MG

Anti-infective function Antiprotozoan - Giardia lamblia

Antimicrobial - H. influenzae, group B Streptococci,

Staph. epidermidis

Antiviral - RSV, HSV-1

______________________________________________________________________________

____________________________

FFA: free fatty acid; MG: monoglyceride; TG: triglyceride; RSV: reticulo syncicial virus; HSV-1:

herpes simplex virus.

* Gastric lipolysis of milk TG higher in human milk-fed (25%) than formula-fed (14%) infants

(1); ** Human milk bile salt dependent lipase enhances intestinal fat digestion in breastfed

infants.

BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D. Professor of Pediatrics,

Department of Pediatrics Georgetown University Medical Center Washington, D.C. 20007-2197

Table 6. Immunomodulating Agents in Human Milk______________________________________________________________________________

Component Function Endogenous production by

infant

IL-1 Production of defense agents in

mammary gland

IL-3 markedly lower by T and

MN cells

IL-4 <10% of adult T cells

IL-5 reduced mRNA expression

IL-6 Regulates function of mammary gland normal in term, reduced in preterm

IL-8 Chemotactic for intestinal intraepithelial reduced mRNA and protein*

leukocytes

IL-10 Modulates epithelial barrier integrity 15-20% of adult level*

IL-12 Enhances production of inflammatory

cytokines ?

INF-g Modulates epithelial barrier integrity <10% of adult level

TNF-a Regulates function of mammary gland ~20-50% of adult level

TGF-b Anti-inflammatory

______________________________________________________________________________

____________________________

Cytokines IL-1b, IL-6, IL-8, INF-g and TNF-a are proinflamatory, whereas IL-10 and TGF-b are

anti-inflammatory

* After stimulation of mononuclear cells (IL-8), and Lps or TNF-a (IL-10).BIOACTIVE FACTORS IN HUMAN MILK Margit Hamosh, Ph.D. Professor of Pediatrics,

Department of Pediatrics Georgetown University Medical Center Washington, D.C. 20007-2197

Table 7. Antiinflammatory Components of Human Milk______________________________________________________________________________

Component Function

Vitamins A Scavenge oxygen radicals

C Scavenge oxygen radicals

E Scavenge oxygen radicals

Enzymes Catalase Degrades H2O2

Glutathione peroxidase Prevents lipid peroxidation

PAF*-acetylhydrolase Degrades PAF, a potent ulcerogen

Antienzymes a-1-antitrypsin inhibit inflammatory proteases

a-1-antichymotrypsin inhibit inflammatory proteases

Prostaglandins PGE1 cytoprotective

PGE2 cytoprotective

Growth factors EGF Promotes gut growth and functional

maturation

TGF-a Promotes epithelial cell growth

TGF-b Supresses lymphocyte function

Cytokines IL-10 Supresses function of macrophages, NK & T

cells

Cytokine receptors TGF-a - RI, RII Bind to and inhibit TGF-a

______________________________________________________________________________

_________________________________

*PAF: platelet activating factor.

Table 8. Enzymes with Digestive Function in the Infant______________________________________________________________________________

Characteristic Lipase (BSDL) Amylase

Maternal Factors

Parity (=10) ? Low activity

Diurnal and within feed activity Constant Constant

Secretion

Prepartum* Present ?

Postpartum Constant Decrease before

1st month

Preterm vs. term delivery** Equal activity Equal activity

Milk characteristics

Distribution Skim milk Skim milk

Storage (-20o,-70 o) Stable years Stable years

Storage (15-38 o) Stable (24 hrs) Stable (at least 24 hrs)

Stability to pH (stomach) >3.0 >3.0

pH optimum 7.4-8.5 6.5-7.5

Enzyme characteristics Identical to pancreatic CEL Isoenzyme of

salivary amylase

Evidence of activity in infants yes yes

Present in milk of other species Primates, carnivores,rodents ?

______________________________________________________________________________

__________________________________

BSDL: bile salt dependent lipase; CEL: cholesteryl ester lipase

* Prepartum - 2-3 months secretion; ** Infants delivered preterm (26-36 weeks gestation) and

term (37-40 weeks) gestation.

Table 9. Hormones in human milkHormone Concentration Milk:Plasma Mammary Effects newborn

/mL Ratio SynthesisPituitary

PRL 20-90ng >1.0 yes

Neuroendocrine

GH 5-30mU >1.0 ?

TSH 2.7-5.0mU <1.0 ? T3/T4

levels

Hypothalamus

TRH 0.025-1.5ng >1.0 no GH,

TSH

LHRH ? ? ? ?

Somatostatin 23-113pg >1.0 no ?

GnRH 0.1-4.0ng >1.0 yes ovarian

receptors

GHRH 23-430pg >1.0 ? GH

secretion

Thyroid

Thyroxine(T4) 0.3-12ng ? yes

Triiodothyronine 0.2-0.4ng ? yes

ReverseT3 (rT3 ) 0.008-0.15ng ? ?

Parathyroid

Parathormone(PTH) 15pg ? ?

PTH related peptide 30-50ng >1.0 yes

Calcitonin/CIP 0-5ng ? ?

Steroid

Estrogen 15-840 ng >1.0 yes

Progesterone 10-40 ng =1.0 no

Adrenal steroids 0.2-32ng <1.0 ? organ maturation

Table 10. Growth Factors in Human MilkGrowth Factor Concentration Milk:Plasma Mammary Effects in the newborn

/mL Ratio Synthesis

______________________________________________________________________________

EGF 3-107ng >1.0 yes GI growth and

gut closure

NGF ? ? ? ?

Insulin -20 mg >1.0 yes glycemia

IGF-I 1.3-11.0ng >1.0 yes stimulate

systemic growth

not epithelial

IGF-II ? >1.0 yes

TGF-α 0-8.4ng GI growth

Relaxin 0.3-0.5mg >1.0 ?

TGF-β ? ? ? inhibits GI growth

______________________________________________________________________________

Table 11. Erythropoetin, Melatonin and Leptin in Human Milk______________________________________________________________________________

Erythropoetin* Melatonin**

Leptin***

day night

Concentration in milk 11.7±0.75 <43 99 73

Concentration in mother’s serum 3.4-24.8 280 9-18

Concentration in infant’s serum 14.2±0.81 ? decrease pp#

Synthesis in mammary gland ? ? ?

Distribution in milk skim milk fat globules

Concentration throughout lactation < 2 months < ? ?

Absorption by newborn probable yes yes

Function in newborn ? awareness ?

______________________________________________________________________________

______________________________

*: mU/mL; **: fm/mL; ***: ng/mL; #: pp: post partum