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Differences in chemical composition between cow colostrum and milk



Summary Penchev Georgiev, I., 2008. Differences in chemical composition between cow colostrum and milk. Bulg. J. Vet. Med. , 11, No 1, 312. The aim of the present paper is to review the differences in chemical composition between colostrum and milk in cows. The concentrations of many nutrients (proteins, vitamins, minerals etc.) and bio- logically active substances (immunoglobulins, enzymes, hormones, growth factors etc.) are many times higher in colostrum than in milk. A special attention is given to insulin-like growth factors (IGF-1 and IGF-2)  the predominant growth factors in the colostrum of cows (especially in the first portions) unlike many other species and men. Furthermore, IGF-1 and IGF-2 are the most important factors stimulating tissue and body growth and development in newborn calves.
Bulgarian Journal of Veterinary Medicine (2008), 11, N
1, 312
Department of Pharmacology, Animal Physiology and Physiological Chemistry,
Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
Penchev Georgiev, I., 2008. Differences in chemical composition between cow colostrum
and milk. Bulg. J. Vet. Med., 11, No 1, 312.
The aim of the present paper is to review the differences in chemical composition between colostrum
and milk in cows. The concentrations of many nutrients (proteins, vitamins, minerals etc.) and bio-
logically active substances (immunoglobulins, enzymes, hormones, growth factors etc.) are many
times higher in colostrum than in milk. A special attention is given to insulin-like growth factors
(IGF-1 and IGF-2) the predominant growth factors in the colostrum of cows (especially in the first
portions) unlike many other species and men. Furthermore, IGF-1 and IGF-2 are the most important
factors stimulating tissue and body growth and development in newborn calves.
Key words: chemical composition, colostrum, cows, insulin-like growth factors, milk
The formation of colostrum in cow’s ud-
der occurs during the first 57 days after
calving. Its composition is similar to that
of blood and differs significantly from
milk. Colostrum contains both nutrients
(proteins, fats, lactose, essential fatty
acids and amino acids) and non-nutrients
(biologically active substances). This is
the first food for neonates after the partu-
rition that provides them with all neces-
sary nutrients. Also, colostrum is particu-
larly important for the passive immuniza-
tion of the newborn, as the combination of
its various specific (immunoglobulins, Ig)
and non-specific (humoral and cellular)
antibacterial factors passes in the off-
spring and largely supports their protec-
tion against infections during the first days
after birth (Tomov, 1984; Medvezki,
1989; Iliev & Tomov, 1992; Blum &
Hammon, 2000; Playford et al., 2000). It
is also considered that the high concentra-
tions of growth factors in cow colostrum
(mainly insulin-like growth factors 1 and
2 IGF-1 and IGF-2) and hormones (in-
sulin) control the growth and development
of gastrointestinal tract and contribute for
the functional maturation of the organism
during the first days after birth (Blum &
Hammon, 2000; Blum & Baumrucker,
2002; Sauter et al., 2004; Blum, 2006).
The aim of the present paper was to
review and analyze the available informa-
tion upon the differences in the composi-
tion between cow colostrum and milk.
Compared to milk, colostrum contains
higher levels of proteins lactalbumins,
Differences in chemical composition between cow colostrum and milk
BJVM, 11, No 1
lactoglobulins and especially immu-
noglobulins (IgG
, IgG
, IgM, IgA), pep-
tides (lactoferrin, transferrin), hormones
(insulin, prolactin, thyroid hormones, cor-
tisol), growth factors, prostaglandins, en-
zymes, cytokines (tumor necrosis factor-
α), acute-phase proteins
nucleotides, polyamines, minerals (iron,
magnesium and sodium salts), (pro)vita-
mins: especially β-carotene, vitamins A,
Е, D, B, cell elements lymphocytes,
monocytes, epithelial cells etc. (Gerov et
al., 1987; Medvezki, 1989; Blum &
Hammon, 2000; Ontsouka et al., 2003;
Blum, 2006). The concentrations of most
ingredients, especially those of immu-
noglobulins (Ig) and growth factors, are
the highest in the first portions colostrum
immediately after calving, and thereafter
are rapidly decreasing (Rauprich et al.,
2000a; 2000b; Blum & Hammon, 2000;
Playford et al., 2000; Kirk, 2005; Blum,
2006). It should be noted that Ig account
for more than 50% of the total amount of
colostrum proteins and contain almost all
antibodies, encountered in maternal blood
(Tomov, 1984), about 90% of colostrum
Ig being from the IgG
type. At the same
time, the contents of lactose and casein in
colostrum are lower than those in milk
(Ontsouka et al., 2003).
Many of non-nutrient e.g. biologically
active substances of colostrum come di-
rectly from the blood, for instance, IgG,
somatotropin, prolactin, insulin and glu-
cagon. Other non-nutrients are locally
produced in the udder from lactocytes and
the stroma.
Both the nutritive and immune-related
functions of colostrum are essential for
newborn calves. Experimental data sug-
gest that unlike that in women, the pla-
centa of ruminants is not permeable to
macromolecules such as Ig from the ma-
ternal blood (Мedvezki, 1989). That is
why calves are born with very weak
mechanisms of defense and are particu-
larly susceptible to various infections.
According to numerous data, blood serum
of calves prior to suckling colostrum lacks
Ig, or contains only traces of Ig, whereas
the bactericidal and lysozyme activities
and the alternative pathway of comple-
ment activation (APCA) are very low or
absent (Tomov, 1984; Gerov et al., 1987;
Iliev, 1988; Tomov et al., 1989; Levieux,
1999). Therefore, the intake of colostrum
in the first hours after birth is extremely
important for increasing the specific and
non-specific resistance of calves against
harmful pathogens, causing alimentary,
respiratory and other disorders in the
postnatal period (Kirk, 2005).
Calves obtain antibodies ready-to-use
under the form of Ig, mainly from the
, IgG
, IgM and IgА classes with co-
lostrum the so-called colostrum antibo-
dies, bound to the globulin protein frac-
tion (Iliev, 1988; Medvezki, 1989; Tomov
et al., 1989; Blum, 2006). Colostrum
globulins are identical to those of mater-
nal blood serum and during the first days
of life, pass in the blood of calves through
alimentary tract epithelium (Medvezki,
1989). According to Tomov et al. (1989),
during the first hours after birth, IgM are
absorbed more rapidly whereas IgG are
mostly retained on the apical surface of
the intestinal mucous coat, and exert there
a local protective function. Also, there is a
correlation between blood serum Ig of
newborn calves and both peripheral blood
cortisol and maternal blood cortisol, con-
firming the view that in physiological
concentrations, glucocorticoids stimulate
antibody formation (Tomov et al., 1989).
The earliest colostrum intake is of
primary importance for the passive immu-
nization of calves, when colostrum’s value
is the most complete from biological point
I. Penchev Georgiev
BJVM, 11, No 1
of view (high titre of colostrum Ig, high
lysozyme, bactericidal and APCA activi-
ties, high content of growth factors), the
permeability of the epithelium of small
intestine is the highest, and the acidity of
abomasum content the lowest due to the
lack of hydrochloric acid (Iliev, 1988;
Gueorguiev et al., 1996; Kirk, 2005). Re-
gardless of the fact that the content of
biologically active substances in colos-
trum is preserved relatively high up for
24–36 hours, it is most appropriate that
the intake of first colostrum occurs within
6 hours after calving, when Ig concentra-
tions are the highest (Kirk, 2005). Iliev
(1988) observed maximum values of IgG,
vitamin A, carotene and vitamin C in the
first portions of colostrum immediately
after the parturition, this high level being
persistent for 24 hours, and thereafter de-
creasing by the 5
and the 12
Ig are absorbed by small intestine mu-
cosa by pinocytosis for a relatively short
time (812 hours after birth). Then, the
permeability of intestinal mucosa in calves
strongly decreased and becomes entirely
impermeable after the 36
hour, in lambs
after the 3
day (Tomov, 1984; Gerov,
1987). The absorption times of the differ-
ent Ig classes are different. Thus, the ab-
sorption of IgG stops after the 27
and that of IgA after the 16
hour follow-
ing birth (Gerov, 1987). It is established
that the strong reduction of colostrum Ig
occurs simultaneously with the so-called
closure period of small intestine epithe-
lium with regard to the absorption of large
macromolecules, including Ig.
The highest proportion of colostrum Ig
consists of IgG, mostly IgG
that accounts
for 90% of all Ig and at a lesser extent
(Levieux, 1999; Ontsouka et al.,
2003). The content of these Ig in colos-
trum depends on their blood concentra-
tions. IgG content in the first portions
varies within a very wide range in the dif-
ferent cattle breeds from 18 mg/mL
92 mg/mL (Kiddy et al., 1971, McGuire
et al., 1983). According to Levieux
(1999), the colostrum IgG level in Hol-
stein-Friesian cattle immediately after the
parturition was about 60 mg/mL, in Hol-
stein 50 mg/mL, and in meat-type
breeds was higher 100 mg/mL. It should
be noted that IgG
concentration de-
creases twice in every subsequent milking
and by the 7
day, is about 1 mg/mL,
reaching normal milk values by the 2
month: 0.250.5 mg/mL (Levieux,
1999). IgG
in colostrum varies from 1.6
mg/mL 6.4 mg/mL, whereas in normal
milk its concentration is about 0.05
The class M immunoglobulins (IgM)
in colostrum vary between 5 mg/mL and
8.7 mg/mL whereas in milk their concen-
trations are 0.040.05 mg/mL (Levieux,
1999). Colostrum and milk IgA levels are
1.7 and 4 mg/mL, respectively. The con-
tent of β-lactoglobulin and α-lactoglobulin
in colostrum is also higher than in milk
(14 and 2 mg/mL vs 4.5 and 1.46 mg/mL,
respectively). Colostrum contains rela-
tively high amounts of lactoferrin (1.22.6
mg/mL), albumin (1.22.66 mg/mL) and
transferrin (0.91.07 mg/mL), that decline
very rapidly reaching normal values in
milk of 0.15-0.30 mg/mL by the 8
day (Levieux, 1999). By immunoelectro-
phoresis, some acute-phase proteins as α
glycoprotein are discovered in colostrum.
Its concentrations range between 1 and
1.65 mg/mL in colostrum and 0.09–0.016
mg/mL in milk (Mesa et al., 1994).
Our previous data (Georgiev, 2005)
demonstrate that the chemical composi-
tion of colostrum (dry matter, solid non-
fat extract, lactose, milk fat and protein)
changes very rapidly with time, so that by
the 3
day post partum it is already simi-
Differences in chemical composition between cow colostrum and milk
BJVM, 11, No 1
lar to that of normal milk. These results
correspond to the data of Kráčmar & Ze-
man (2004). The lysozyme activity in the
colostrum of cows with high and low milk
yield changes from 0.401±0.09 µg/mL
and 0.327±0.07 µg/mL at parturition to
0.096±0.03 µg/mL and 0.073±0.01 µg/mL
on the 3
post partum day, respectively
(Gueorguiev et al., 1996).
The most consistent changes occur in
milk protein content that is reduced more
than twice by the 3
post partum day
compared to initial values. This is mostly
due to the sharp decrease in Ig fractions
(Ontsouka et al., 2003), whose concentra-
tion, as already mentioned, was the high-
est in the first colostrum portions (Ont-
souka et al., 2003). It was also found out
that the differences in milk secretion rates
had no significant effect upon the chemi-
cal composition of colostrum as the dif-
ferences in the concentrations of fats, pro-
teins, lactose, dry matter and the solid
non-fat extract among cows with different
milk yields were low and statistically in-
significant. Furthermore, the differences
in the milk yield of cows did not affect
noticeably the levels of lysozyme in colos-
trum and in the blood of neonatal calves
(Gueorguiev et al., 1996).
Cow colostrum contains also compo-
nents with concentration lower than 1
mg/mL (trace components). These are
various proteins, enzymes, enzyme inhibi-
tors, hormones, growth factors, vitamins,
macro- and trace elements etc. Despite
their low concentrations, trace compo-
nents are physiologically important for
both the local protection of the udder and
the growth and development of neonates.
Using cross electrophoresis, more than 30
proteins are detected in colostrum apart
those already mentioned IgG, IgA, IgM,
β-lactoglobulin, α-lactalbumin etc. (Levi-
eux, 1999). According to data from this
author, colostrum contains some proteins
of blood origin prealbumins, C3 com-
ponent of complement, haptoglobin and
others, that together with lysozyme, lacto-
ferrin, properdin, the lactoperoxidase-
thiocyanate-hydrogen peroxide system,
exhibit a strong antibacterial effect and
are essential elements of the local non-
specific resistance. The concentration of
all those proteins in colostrum is consid-
erably higher than in milk. From colos-
trum and milk are isolated also β
microglobulins with concentrations of 6
and 2 µg/mL, respectively, as well as bra-
dykinin, various kininogens etc. (Levieux,
Milk and colostrum contain about 60
enzymes, most of them being identified as
endogenous: glucose-6-phosphate isome-
rase, phosphodiesterase, α-manosidase,
galactosyltransferase (Levieux, 1999).
Of all enzymes present in milk, the
highest content is that of lactoperoxidase
0.03 mg/mL. In colostrum, the levels of
this enzyme increase rapidly after birth
and peak by the 4
day, and thereafter
gradually decrease. The activities of alka-
line phosphatase and N-acetyl-β-glucosa-
minidase are 5 and 20 times higher in co-
lostrum compared to milk, respectively
(Levieux, 1999). The activity of the cell
membrane-bound enzyme γ-glutamyl
transferase in colostrum (19000 U/L) is
2.53 times higher than in milk and 300
times compared to serum (Vacher &
Blum, 1993).
Of proteinases group, the amount of
plasmin in milk is the highest. Its concen-
tration in colostrum is about 10 times
higher than that of milk, 0.49 µg/mL and
0.04 µg/mL (Dupont et al., 1998). The
presence of cathepsin D that breaks down
caseins (α-S1, α-S2, β), α-lactalbumin, but
not β-lactoglobulin is also detected (Lar-
sen et al., 1996).
I. Penchev Georgiev
BJVM, 11, No 1
Colostrum and milk contain a number
of enzyme inhibitors that protect udder
tissues from the proteolytic effect of leu-
kocyte proteases. The concentration of
enzyme inhibitors is the highest in the first
portions of colostrum and then decreases
rapidly. The α-macroglobin (390 µg/mL
in colostrum and 4.5 µg/mL in milk), α
antitripsin (250800 µg/mL in colostrum,
620 µg/mL in milk) belong to this group
(Levieux, 1999). Other low-molecular
enzyme inhibitors (1260 kDa) are also
isolated from colostrum with a not entirely
obvious physiological role: serine and
cysteine protease inhibitors, α
min, plasminogen activator inhibitor etc.
A number of hormones are detected in
colostrum and milk, whose concentrations
in the first colostrum are many times
higher than in milk (Levieux, 1999) (Tab-
le 1).
Table 1. Contents of some hormones in colos-
trum and milk
colostrum: 4.234.4 ng/mL
milk: 0.0420.34 ng/mL
Total cortisol
colostrum: 4.4 ng/mL
milk: 0.35 ng/mL
Free cortisol
colostrum: 1.8 ng/mL
milk: 0.3 ng/mL
colostrum: 150 ng/mL
milk: 50 ng/mL
colostrum: 2.6 ng/mL
milk: 0.8 ng/mL
The content of oestrogens (oestron,
oestradiol-17β) in colostrum is similar to
that of plasma and almost twice higher
than that of milk. The levels of somato-
tropin and thyroxine however are higher
in milk than in colostrum (Blum &
Hammon, 2000).
Many growth factors are isolated from
cow colostrum. They are discovered in the
beginning of the 80-ties of the last cen-
tury, but are not fully investigated. At
present, the physiological importance of
the following main growth factors in cow
colostrum is studied: IGF-1, IGF-2; colos-
tric basic growth factor, prolin rich poly-
peptide etc. (Levieux, 1999). Some of
them are absorbed in very low amounts
and exert a local stimulating effect upon
the growth and development of the gastro-
intestinal tract of newborn calves, whereas
others, together with endogenous growth
factors, are essential for the growth and
development of the other organs.
The highest proportion of cow colos-
trum growth factors is that of insulin-like
growth factors (IGFs). IGFs could originate
from blood or be synthesized in the udder.
There are species-related differences in the
content of growth factors in colostrum. For
instance, in human milk predominates the
epidermal growth factor, that is not found
in cow colostrum, where IGF-1 is the most
abundant. Growth factors in human milk
persist at relatively high levels during the
entire lactation period whereas in cows,
their concentrations are high only in the
first portions of colostrum and then, rapidly
decrease (Blum & Hammon, 2000; Rau-
prich et al., 2000 а; 2000b).
The concentrations of IGFs and insulin
are higher in colostrum than in blood
unlike some hormones (somatotropin,
glucagon and thyroid hormones). The
levels of growth factors, insulin and other
peptides is different in the various colos-
trum portions, being the highest in the cis-
ternal fraction, then decreasing and rising
again by the end of milking, respectively
suckling. This determines the differences
in the delivery of these components to
Differences in chemical composition between cow colostrum and milk
BJVM, 11, No 1
suckling calves with the different colostrum
fractions (Ontsouka et al., 2003).
Little is known about the physiological
characteristics of IGFs. It is suggested that
in neonatal calves they are essential for
the regulation of growth and development
of the GIT, affecting cellular proliferation
and differentiation.
IGF-1 and IGF-2 are single-chain low-
molecular polypeptides with proinsulin-
like structure. Among the more important
physiological effects of IGFs are their
effects upon the transmembrane transport
and metabolism of glucose, amino acids,
nucleotides etc. Also, IGFs stimulate the
synthesis and inhibit the breakdown of
proteins, DNA, RNA and regulate cell
proliferation and differentiation in tissues,
at the same time inhibiting apoptosis
(programmed cell death) (Disenhaus et
al., 1988; Bühler et al., 1998; Jehle et al.,
1999; Brеier et al., 2000; Blum, 2006).
The concentration of IGF-1 in cow co-
lostrum (383500 µg/L) is many times
higher than in women’s colostrum (18
µg/L) (Baxter et al., 1984; Vacher &
Blum, 1993; Rauprich et al., 2000a;
2000b). The lowest IGF-1 level is that of
cow milk (410 µg/L) (Collier et al.,
1991; Ontsouka et al., 2003). It should be
noted that IGFs are not species-specific
and are not destroyed during milk pas-
teurization at 79
С for 45 s, as well as by
gastric juice acidity (Collier et al., 1991;
Lowe 1991). IGF-1 is destroyed after heat-
ing milk to 121
С for 5 min (Collier et al.,
1991). It was also established that at the
beginning of lactation, milk IGF-1 level is
higher compared to that in middle lacta-
tion and correlates negatively to milk pro-
ductivity (Collier et al., 1991).
About the origin of IGFs in colostrum
and milk, it is proved that a part could go
through from blood into milk by transport
via the mammary alveolar epithelium
(Vega et al., 1991). More recent data,
based on polymerase-chain reaction and
immunohistochemistry show that IGF-1,
IGF-2 and the insulin-like growth factor
binding proteins (IGF-BP) are produced
locally, not in secretory cells, but in adi-
pocytes, fibroblasts and blood vessels’
smooth muscles, their expression varying
during the different physiological states of
the udder mammogenesis, lactogenesis,
lactopoiesis and involution (Plath-Gabler
et al., 2001). It is also found out that in
colostrum, IGFs could be either free or
bound to IGF-BP. The free (biologically
active) forms prevail during the perinatal
period whereas bound forms are prevalent
in milk (Schams & Einspanier, 1991;
Playford et al., 2000). Although the exact
role of IGF-BP is not completely known,
it is thought that they are important for
regulation of the IGFs binding to their
receptors. (Playford et al., 2000). It is also
demonstrated that one of IGF-BP, namely
IGF-BP-3, binds also lactoferrin (Blum &
Baumrucker, 2002). IGF-BP-3 and lacto-
ferrin enter the nuclei of glandular epithe-
lial cells and there, via yet unknown
mechanisms, influence apoptosis, there-
fore they are important for the involution
of the mammary gland (Blum & Baum-
rucker, 2002).
As mentioned above, IGFs concentra-
tion is the highest in the first portion of
colostrum, then decreases rapidly and in
milk, they are found at levels, many times
lower than in colostrum (Rauprich et al.,
2000 a; 2000b). Therefore, the intake of
colostrum during the first hours after birth
is extremely important to provide the
needed nutrients (proteins, carbohydrates,
lipids, vitamins, minerals etc.) and for the
normal growth and the morphological and
functional maturation of the gastrointesti-
nal tract of the organism, i.e. for the ade-
quate adaptation of newborns to the new
I. Penchev Georgiev
BJVM, 11, No 1
environment, especially in the early post-
natal period when the abrupt change from
parenteral nutrition in the foetal period to
exceptionally enteral nutrition after the
birth occurs (Blum, 2006). The normal
accomplishment of all these events is
regulated by the high content of biologi-
cally active peptides, growth factors, hor-
mones, cytokines etc. in colostrum
(Hammon & Blum, 1997; Hadorn et al.,
1997; Blum & Hammon, 2000; Playford
et al., 2000; Blum, 2006). This view is
supported by the studies of Roffler et al.
(2003), showing that the stimulating effect
of colostrum upon the growth of the gas-
trointestinal tract in newborn calves is due
not only to IGF-1, but rather to an entire
set of growth factors, as the exogenous
application of first colostrum extract,
where growth factors are the most abun-
dant, stimulated at a greater extent the size
of intestinal villi than the administration
only of IGF-1 did.
Apart IGFs, cow colostrum and milk
contain other growth factors from the
group of transforming growth factors
(TGF) TGF-α; TGF-β at lower concen-
trations. Their levels in colostrum (20–40
mg/L) are significantly higher than in milk
(1–2 mg/L) (Playford et al., 2000). Al-
though their precise physiological role is
not entirely clear, it is suggested that they
are involved in the proliferation of intesti-
nal epithelial cells (Playford et al., 2000).
As TGF-α and TGF-β are expressed at
considerable amounts in cow’s udder, they
are believed to participate in the regula-
tion of proliferation and reorganization of
the glandular parenchyma during the
mammogenesis, lactogenesis, lactopoiesis
and involution (Plath et al., 1997).
By the 7
day after birth, serum levels
of γ-globulins, glucose, albumin, essential
and non-essential amino acids, triglyce-
rides, cholesterol, insulin, IGF-1, thyroid
hormones and prolactin were statistically
significantly higher in calves that suckled
colostrum immediately after calving than
in calves, receiving colostrum after 23
days (Hadorn et al., 1997). The delay in
colostrum intake by 24 hours results in
sharp increased in the concentrations of
non-esterified fatty acids, an indicator of
energy deficiency in calves. Furthermore,
the intake of full value colostrum in-
creases to a large extent the absorption
capacity of small intestine that is essential
for the complete utilization of nutrients
and immunoglobulins (Hammon & Blum,
1997; Blum & Hammon, 2000). All those
data evidence the strong stimulating effect
of colostrum on anabolic processes in the
In order to manifest their effect, IGF-1
and IGF-2 are bound to specific receptors,
present in many tissues of neonatal calves,
including the gastrointestinal tract, the liver
etc. (Hammon & Blum, 2002; Ontsouka et
al., 2004a; 2004b). It is established that
growth factors receptors are present mainly
to the basolateral membrane of mucosal
epithelial cells, rather than on the apical
surface, that would impede the direct effect
of growth factors ingested with colostrum
(Playford et al., 2000). During the early
postnatal period however, the intestine per-
meability to many of colostrum ingredients,
including growth factors, is considerably
higher, facilitating the binding of these fac-
tors to their receptors and hence, their ef-
fect on gut growth and development
(Playford et al., 2000).
Factors such as the rearing technology
and nutrition during the pregnancy, and
especially during the dry period, the
health status of cows etc. have an impact
on colostrum composition and its biologi-
cal value. The reduced biological value of
colostrum has a rather negative effect on
the status of newborn calves, with regard
Differences in chemical composition between cow colostrum and milk
BJVM, 11, No 1
to their vitality, weight gain, specific and
non-specific resistance (Tomov, 1986;
Iliev, 1988; Blum, 2006). Iliev (1988)
established a direct correlation between
the maternal blood lysozyme, comple-
ment, bactericidal and phagocytic activi-
ties and Ig content, the biological value of
colostrum and blood serum concentrations
of these parameters in newborn calves
during the first days of life. The author
has also found out that the colostrum of
cows, reared in stalls, contained conside-
rably lower levels of Ig, lysozyme, vita-
mins and С) compared to cows, reared
either in stall and pasture or freely in
boxes. The offspring of immobilized cows
exhibited lower lysozyme and comple-
ment activities, Ig and vitamin A and C
levels. This is explained by the systemic
strain in immobilized cows, accompanied
by increased incretion of some stress hor-
mones ACTH, cortisol, that in supra-
physiological concentrations exert sup-
pressive effect on antibody formation and
systemic immune status (Iliev, 1988).
In conclusion, we could summarize
that there are significant differences in the
chemical composition between colostrum
and milk. The concentration of many nu-
trients (proteins, vitamins, minerals etc.)
and biologically active substances (Ig,
enzymes, hormones, growth factors etc.)
is many times higher in colostrum than in
milk. Of growth factors, cow colostrum is
the richest in IGF-1 and IGF-2, especially
in the first portions. These factors, to-
gether with insulin, play a very crucial
role in controlling the growth and deve-
lopment of gastrointestinal tract and the
organism in newborn calves during their
first days of life, when a sudden change in
the mode of nutrition from entirely paren-
teral during the foetal stage to entirely
enteral after birth does occur.
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Paper received 23.04.2007; accepted for
publication 12.11.2007
Assoc. Prof. I. Penchev Georgiev
Department of Pharmacology, Animal
Physiology and Physiological Chemistry,
Faculty of Veterinary Medicine,
Trakia University, Student Campus,
6000 Stara Zagora, Bulgaria
... The mean concentration of growth hormone is far greater in BC (41 ng/L) than mature milk (0.03 ng/L). The concentrations of total and free cortisol hormone in BC were found to be 4.4 and 1.8 ng/ml, respectively, while the respective concentrations of total and free cortisol hormone in mature milk is 0.35 and 0.3 ng/ml (Georgiev, 2008). Regulation of the hormones occurs via hypophyseal (somatostatin, prolactin, oxytocin), thyroid (calcitonin and thyroxine), sexual (progesterone and estrogen), and some other body systems. ...
... Regulation of the hormones occurs via hypophyseal (somatostatin, prolactin, oxytocin), thyroid (calcitonin and thyroxine), sexual (progesterone and estrogen), and some other body systems. These regulated hormones have positive effects on the growth and development of organs, celiac disease, and many physiological conditions (Georgiev, 2008;Playford et al., 2000). ...
... Due to this low-level of lactose, colostrum produces more viscous and has less water in it due to the absence of lactose osmoregulator. Lactose consists of glucose and Source: Buttar et al., 2017;Farkye, 2002;Georgiev, 2008;Hanušovský et al., 2014;Kehoe et al., 2011;McGrath et al., 2016;Miciński et al., 2017;Ontsouka et al., 2003;Poulsen et al., 2010. ...
ABSTRACT: Bovine colostrum (BC) consists of highly concentrated nutritional and bioactive components after parturition. BC supplements are promoted for prevention and management of neurological disorders (dementia, cognition, Parkinson's disease, and Alzheimer's disease), cardiovascular diseases, immunity-related and allergy problems, skin disorders, inflammatory bowel disease, gut microbial symbiosis as well as type-2 diabetes, and improved athletic performance. This review provides succinct insights into emerging evidence from preclinical and clinical studies which suggest that BC constituents have enormous potential in nutraceuticals and non-pharmacological therapies. The overall composition, factors affecting, traditional and commercial products, health attributes of bovine colostrum particularly, B-type vitamins, oligosaccharides, immunoglobins, growth factors and the role of lactoferrin and lactalbumin in cancer therapy, are also briefly explained. Naturally produced bioactive components, immunoglobulins lay the foundation of life-long immunity, while the other components in colostrum promote growth and maturation of the gastrointestinal tract as well as promote differentiation of bone marrow stem cells, increase lean muscle mass, and decrease the body fat level. The bovine colostrum is rich in versatile iron-binding lactoferrin that has strong anti-oxidant, anti-inflammatory, anti-carcinogenic, and anti-microbial properties. Additionally, BC products like ginna, kharwas, aguz, and processed BC supplements like colostrum powder, capsules, and infant-formulas are marketed by many companies all over the world. Considering the escalating cost of synthetic drugs, people in developing countries are desperately looking for affordable and cost effective therapies for curing the non-communicable diseases (NCDs) and infectious diseases. It will be interesting to see if BC might have viricidal effects against COVID-19 virus.
... This may be one of the explanations in that IGF-1 level at birth was slightly increased in favor of dams that gave birth to males. The concentration of IGF-1 was higher in the colostrum, compared to the dam's blood unlike some other hormones as somatotropin, glucagon, and thyroid hormones (Georgiev, 2008). Ashmawy (2015a) indicated that colostrum has a higher concentration of IGF-1 hormone than in mature milk, but it rises again by the end of milking. ...
... It was previously reported by Brian et al. (2016) that immunoglobulins make up 70-80% of the total protein in colostrum, which represent most of the immune bodies transported from maternal blood to colostrum. Additionally, about 90% of colostrum immunoglobulins are being in the form of IgG (Georgiev, 2008), and the whey protein values of the colostrum samples obtained from the animals gave male calves were significantly higher than those animals that gave female calves (Nazir et al., 2018). This result agreed with Ashmawy (2015a) who indicated that the most consistent change occurring in the chemical composition of colostrum is in protein content where it is reduced by half of its concentration at one day postpartum compared to the initial value. ...
An The aim of the present research was to determine the effect of both the gender of the new-born calf and the pre-partum vaccination status of the dam (ScourGuard-4K) on the chemical composition and some biological parameters of the colostrum. Blood serum was collected from four groups of pregnant dams (four animals in each group) during the dry period (vaccinated buffalo dams pregnant with a male fetus, vaccinated buffalo dams pregnant with a female fetus, unvaccinated buffalo dams pregnant with a male fetus, and unvaccinated buffalo dams pregnant with a female fetus), in the pregnancy period, at the giving-birth period and after 24 hours of postpartum. The levels of insulin-like growth factor hormone (IGF-1) and immunoglobuline G (IgG) were calculated in the maternal blood serum at the assigned periods. Colostrum samples were collected at the birth time and 6, 12, 24, 48, and 72 hours after birth for measuring the chemical composition of the colostrum, as well as levels of IgG and IGF-1. Results of the current study showed that colostrum of dams that gave birth to male fetus had a richer content of IgG and IGF-1 levels and a higher percentage of total solids, solids-not-fat, total protein, fat, and lactose. Additionally, vaccination improved the same colostrum components except for IGF-1, which was not positively influenced by the vaccination. Generally, colostrum components were the highest at the birth time, then it decreased gradually up to 72 hours after the birth except that for the percentage of fat and lactose which showed gradual increases up to 72 hours to reach the normal composition of milk.
... profiles, specifically affecting total serum solids (Brix) and plasma IgG. Colostrum management is key to calf rearing, health, and profitability, as newborns rely on both the immune-and nutrient-related qualities of colostrum (39). In the current study, stimulating DMI of cows fed AA during the closeup period resulted in greater energy and total metabolizable protein intake, which supported colostrum quality and was mainly attributed to increased efficiency of indispensable AAs, as discussed in our study (36). ...
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The objective of this study was to evaluate the effect of supplying ruminally-protected lysine (RPL), methionine (RPM), or the two in combination (RPML) to transition dairy cows on the immunity and performance of their offspring. Eighty heifer calves (n = 20 calves per group) were assigned to four treatments based on their dam diet; basal diet (CON), a basal diet with lysine [RPL, 0.33% of dry matter (DM)], a basal diet with methionine (RPM, 0.16% DM), or with the combination (RPML). Calves were fed colostrum from their dams within 2 h of birth. Calves were then fed milk only (d 2–22), a combination of milk and milk replacer (d 23–25), and milk replacer (d 25–60). Starter feed was fed to the calves twice daily after liquid feeding. Calves blood samples were collected after calving on 0, 12, 24, and 48 h and 5 and 7 d after birth. Data were analyzed by SAS software v9.4. Providing ruminally-protected amino acids (RPAA) to transition cows improved colostrum quality compared to the CON (Brix; P < 0.01). Serum total protein concentrations were higher in calves from supplemented cows than in calves from unsupplemented cows (P < 0.01). Calves born to dams in the RPM, RPL, and RPML groups had higher plasma immunoglobulin G (IgG) concentrations 0, 12, 24, and 48 h and 7 d after birth than those born to dams in the CON group (P < 0.05). The percentage of calves with adequate passive immunity transfer was increased with RPM and RPL or the two in combination (P < 0.01). However, there was no difference in the percentage of calves with adequate passive immunity transfer between the RPM and RPL groups (P = 0.21). Calves from cows that receive supplemental RPAA have a greater average daily gain (ADG) than those born to cows in the CON group (P < 0.01). These results indicate that maternal supplementation with RPM or RPL or the two in combination during the periparturient period could be an alternative strategy to improve the performance of calves, especially in accelerated growth programs in calves.
... respectively. Georgiev (2008) investigated that the fat content of colostrum changes very rapidly with time, so that by 3 rd day postpartum, it is already similar to that of normal milk. Similarly, Abd El Fattah et al. (2012) also reported that decrease in fat content, total solid and ash per cent while as increase in lactose per cent during first five days of parturition. ...
Full-text available
Present study was undertaken to determine the composition al changes in colostrum and milk of Hill cow of Uttarakhand during different stages of lactation period. Fifteen colostrum samples per day were collected during first five postpartum days while as six milk samples of Hill cows were collected at fortnightly interval up to 36 weeks of lactation period and were subjected to various physico-chemical analyses. Maximum mean fat, protein, total solid, ash per cent, and electric conductivity in colostrum of Hill cow was observed on first postpartum days as 6.79±0.16, 13.28±0.13, 23.02±0.27, 1.10±0.06 and 3.41±0.23, respectively and later on decreased as postpartum days advances. But lactose per cent and pH showed an increasing trend during first five postpartum days. In milk of Hill cows minimum mean fat (4.26±0.39 %), protein (3.37±0.50 %) and total solids (12.78±0.42 %) per cent were observed in III, VII and IX stage of lactation, respectively and showed an increasing trend as lactation advances. While as maximum mean lactose (4.62±0.51 %) per cent was observed in III stage of lactation and decreased during last stage of lactation. It can be concluded that colostrum of Hill cow was richer in fat, protein, lactose, total solids and ash content as while as its milk had higher content of fat, protein, SNF, total solids and lower pH, electric conductivity and somatic cell count.
... Bio-actives, such as IGFs, are also present in cow colostrum (Francis et al., 1988;Elfstrand et al., 2002;Georgiev, 2008); however, information available on the effect of these bio-actives on the reproductive development of ruminant offspring is limited (Bach, 2012). In regards to future ruminant offspring production, the quantity of IgG obtained from ingesting colostrum affected future milk production in heifers (DeNise et al., 1989;Faber et al., 2005;Cuttance et al., 2019). ...
In contrast to pigs and cattle, research focussed on sheep colostrum is limited, especially regarding measuring and defining colostrum quality. Colostrum is the first mammary gland secretion available to offspring and it is accumulated during the last term of gestation. Colostrum is an essential source of nutrition, immunoglobulins and bio-actives, and adequate consumption significantly increases the neonate's chance of surviving the challenging ex utero environment. Colostrum plays an important role during development of the immune system, post-natal growth and thermoregulation, and also mediates the creation of the ewe-lamb bond. In addition to increasing the neonate's ability to survive, access to colostrum during the neonatal period has the potential to improve the future production, development and reproductive efficiency of lambs, as studies in pigs have shown that access to colostrum during the neonatal period promotes maturation of the reproductive tract and increases reproductive efficiency later in life. Colostrum effects many developmental aspects of the neonate therefore, it is important that it is of high quality to ensure maximum future productivity. This review summarises the information currently available on sheep colostrum, including supporting research conducted in cattle and pigs, with particular focus on the impact of colostrum composition and quality on progeny performance.
... Immuno-supplementation with bovine milk antibodies has been shown to provide local protection to the gastrointestinal tract against disease [2]. The concentration of many nutrients and biologically active substances is many times higher in colostrum than in milk [3]. Historically, bovine colostrum use in India has occurred since the domestication of this animal species [4] and presenting therapeutic action in the fight against influenza in older adult patients [5] and to irrigate the eye during surgeries in the ocular region is documented in an ancient Indian medicine known as Ayurveda [6]. ...
Early Recovery of COVID-19 Patients by Using Immunoglobulins Present in Cow Colostrum Food Supplement-A Clinical Study
... Immuno-supplementation with bovine milk antibodies has been shown to provide local protection to the gastrointestinal tract against disease [2]. The concentration of many nutrients and biologically active substances is many times higher in colostrum than in milk [3]. Historically, bovine colostrum use in India has occurred since the domestication of this animal species [4] and presenting therapeutic action in the fight against influenza in older adult patients [5] and to irrigate the eye during surgeries in the ocular region is documented in an ancient Indian medicine known as Ayurveda [6]. ...
Full-text available
Background: Immunoglobulins in cow colostrum have proven benefits against various dis-eases including recurrent infections. Objective: To evaluate the effect of Immunoglobulins present in cow colostrum for early re-covery in COVID-19 patients. Materials and Methods: Randomized, controlled trial of cow colostrum supplement performed at ‘vishwaraj super speciality hospital’ Pune, Maharashtra, India in September 2020, after appropriate approval by Institutional Ethics Committee. 200 COVID-19 patients were selected by randomization method, in which 100 patients in study group who received colostrum supplement and 100 patients in control group who did not receive colostrum supplement. COVID-19 patients categorized in Mild (n=55), Moderate (n=39) and Severe (n=6) cases, depending on HRCT Chest scan severity score and severity of symptoms present in patients. Results: Comparative statistical analysis done to check any significant difference in days required for cure in the symptoms and hypoxia in between study and control group. The test used was ‘t’ test for two independent samples. Level of significance is less than 0.05(p<0.05).The early recovery is significant in study group compared to control group at significance level 0.05 (p<0.05) for all symptoms in mild, moderate, severe and all combined categories (p<0.05) but not significant for Off O2 day in mild, CRP blood test in moderate, both Off O2 day and CRP blood test in Severe COVID-19 and CRP blood test in all three combined categories (p>0.05). Conclusion: This study concluded that cow colostrum food supplement may be beneficial in COVID-19 patients for early recovery in mild, moderate and severe categories. Further study can be done in critically ill patients admitted in an ICU and those who are on nasogastric tube feed (RT feed). Key words: Cow colostrum, COVID-19, CRP blood test, Early recovery, Early relief from hypoxia, Immunoglobulins
... whey proteins, Ig, lactoferrin, and lysozyme), oligosaccharides, vitamins, minerals, hormones, growth factors, cytokines, and nucleotides than mature milk (McGrath et al., 2016;Penchev Georgiev, 2008). Indeed, it should be mentioned that the compositions of colostrum relied on several factors, e.g., animal breeds, postpartum period, lactation cycle, length of the dry period of cows, animal physiology, animal nutrition, dairy production management, and environmental factors (McGrath et al., 2016;Puppel et al., 2019). ...
The objectives of this study were to characterize and compare non-volatile polar metabolite profiles of bovine colostrum, collected within 1 h and at 72 h after parturition, from crossbred Holstein cows raised in northeastern Thailand. The colostrum serum was characterized and compared using a non-targeted proton nuclear magnetic resonance (1H-NMR) technique combined with chemometric analysis. Results demonstrated that the main effect of post-parturition time provided a significant impact on the physical properties and major chemical constituents of colostrum, while the influence of farm origin and sampling month were likely undetectable. The 1H-NMR technique enabled to identify 45 non-volatile polar metabolites in the samples. Partial least-squares-discriminant analysis (PLS-DA) allowed discrimination of colostrum metabolome not only according to different times after parturition, but also the origins of the farm as well as sampling months. Differential metabolites were statistically identified as potential biomarkers accountable for the discrimination. Besides basic nutritive compounds (amino acids and sugars), several bioactive metabolites such as ascorbate, creatine, carnitine, choline, acetylcarnitine, N-acetylglucosamine, ornithine, orotate, and UPD-glucose could be successfully elucidated. Our finding reveals the application of non-targeted 1H-NMR metabolomics as an effective tool to assess the biomolecular profiles of bovine colostrum and their essential dynamics during the first three days after parturition.
Milk oligosaccharides are the prebiotic gold standard for neonates. This work investigated the concentration and profile of bovine milk oligosaccharides (BMO) in colostrum and other types of liquid feeds. Sialylated BMO displayed a broad range of concentrations (from nearly 1.7 g L⁻¹ to 100 mg L⁻¹) with 3′-sialyllactose, 6′-sialyllactose, and 6′-sialyl-N-acetyllactosamine having the highest concentration in the 1st milking postpartum but decreasing rapidly until reaching a stable concentration at the 3rd–5th milking. While 3′-sialyllactose was present at the highest concentration in all samples, 6′-sialyl-N-acetyllactosamine concentration was higher than 6′-sialyllactose in the 1st milking but lower than 6′-sialyllactose in the 3rd–5th milking. BMO abundance in colostrum was 7–9 fold higher than in other liquid feeds (saleable, non-saleable, and saleable mixed with non-saleable milk). Sialylated BMO were the predominant type in colostrum, whereas neutral non-fucosylated were similar in all feeds. Five fucosylated BMO were also identified.
Maternal colostrum contains immunological and nutritional components that are essential for the calf's survival and health during the first months of life. Immunoglobulins and leukocytes present in colostrum provide the newborn with specific immunity against common infectious pathogens. Colostrum intake is important for normal plasma concentrations of β‐carotene, vitamin A, and vitamin E. Consumption of colostrum can occur naturally by suckling directly from the dam or through artificial human intervention with a nipple bottle or an esophageal feeder. The quality of colostrum is the most important factor in any colostrum management program. Several factors from the dam, calf, general management, and environment can affect adequate consumption of colostrum and absorption of IgG and other immune factors increasing the risk of transfer of passive immunity. Colostrum management programs should ensure production of high quality colostrum, appropriate colostrum collection, and storage of high quality and pathogen‐free colostrum.
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Changes in the colostrum nutritive value were studied in dairy cows of the Czech Red Pied x Holstein (n = 10) from the 2nd to 72nd hour post partum. Of them, five and five animals were in the first and the second (or higher) lactation, respectively. Dry matter (DM) content ranged from 20.37 to 13.78% (mean value 15.61%). Within the first 12 and 72 hours after parturition, the shares of crude protein in DM were more than 60% (14.33 – 9.71%) and nearly 50% (6.34 – 4.06%; mean 5.61%), respectively. Milk fat made one quarter (2.29 - 5.16%; mean 3.72%) and lactose approximately 22% (2.74 - 3.93%; mean 3.43%) of DM content, respectively.
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Georgiev I. Penchev, 2005. Alterations in chemical composition of colostrum in relation-ship to post-partum time. Bulg. J. Vet. Med., 8, No 1, 3539. Experiments were designed to study the alterations in colostrum composition in relationship to post-partum time in dairy cows differing in milk yield. Two groups of 5 cows each, with high or low milk yield, respectively were used. Colostrum samples were collected on day 1 and day 3 after birth. Concentration of the major colostrum constituents (milk protein, lactose, dry matter and solid non-fat extract) changed significantly after birth, the levels on day 3 being similar to those of mature milk. The most signifi-cant changes were those in the concentration of milk protein, that on day 3 was more than twice lower as compared to the first portion of colostrum. There was no effect of milk secretion intensity on chemical composition of colostrum.
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An experiment with two groups of dairy cows, differing in milk yield and their offsprings was performed. This study provides informations about the influence of milk production on lysozyme activity in colostrum and in blood serum of newborn calves. Serum lysozyme activity in calves, which was not significantly different between groups, correlated positively with milk production of cows, but was not closely related to the activity of lysozyme in colostrum.
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Concentrations of IGF-I and IGF-II, and IGF binding proteins (IGFBP) in serum and mammary gland secretions were surveyed during the dry period and early lactation of 30 Holstein cows. Although there was a threefold drop in the concentration of IGF-I in serum from the last week of the dry period to parturition (81 +/- 7 to 24 +/- 3 ng/ml, P less than .01), there was no significant change in serum IGF-II concentration during this period (150 +/- 17 vs 173 +/- 13 ng/ml, P greater than .05). Furthermore, a 57% increase in serum IGF-I was observed from the last week of lactation to the second week of drying off (100 +/- 5 to 157 +/- 8 ng/ml, P less than .05). Changes in serum IGF-II were not observed (126 +/- 11 vs 150 +/- 10 ng/ml, respectively; P greater than .05). Although IGF-I, IGF-II, and IGFBP concentrations in mammary secretions peaked 2 wk before parturition (2.95 +/- 1.1, 1.83 +/- .6, and 7.27 +/- .76 micrograms/ml, respectively), total output/quarter was highest in colostrum (394 +/- 119, 295 +/- 132, and 2,680 +/- 1,967 micrograms/quarter, respectively). Weekly milking of two individual quarters during the dry period did not affect (P greater than .05) IGF-I or IGF-II concentration (ng/ml) or total output (microgram/quarter) and milk yield in colostrum and milk (2 wk and 7 wk) compared with the ipsilateral quarter. The data support the hypothesis that IGF-I may be transported by the mammary gland epithelium. Furthermore, the secretion mechanisms of IGF-I, IGF-II, and IGFBP by the gland may be related to each other.
To determine by ELISA the variation of plasmin (PLM) and plasminogen (PLG) with lactation and the origin of this variation, 18 high-yielding Holstein cows were milked during 1 year, throughout pregnancy. PLM, PLG, immunoglobulin G (IgG), serumalbumin (BSA), somatic cell (SCC), protein content (PC) and milk yield (MY) were determined in these individual milks. It was observed that parturition is accompanied by a dramatic increase in PLM, PLG, IgG, BSA, PC and SCC and with decrease in MY. The intense increase in the blood-originating proteins in milk proves that calving is characterized by an important influx of blood into milk.
Colostrum, a milk particulariy rich in numerous components. Is it possible to detect its unlawful addition in milk supplies? The concentration of numerous proteins, enzymes, hormones, growth factors, vitamins, minerai and trace elements decreases abruptly during the first milk- ings post-partum and then increases in late lactation and during the udder involution before calving. Therefore, colostrum cannot be precisely defined since it is a milk ail the more abnormal than it is milked closer from calving. So its unlawful addition to milk supply may only be detected by the modification of the normal composition of the' milk. From ail the components reviewed, IgG are the most documented and sensitive indicators of an abnormai milk. They can he easily quantified using a semi-automatised single radial immunodiffusion technique and threshold values characteristic of an abnormal milk have been defined taking into account the volume of the milk supply. © Inra! Elsevier, Paris. colostrum / milk quality / IgG / automatised radial immunodiffusion
Newborn calves are characterised by marked cardio-respiratory, metabolic and endocrine changes which continue during ensuing weeks and months. Thus, although the somatotrophic axis is basically functioning in neonatal calves, it is not yet mature. The speed of the adaptations of the various traits differs widely. The ability to digest colostrum and milk requires specific structures and functions of the gastrointestinal tract. Colostrum composition exhibits major changes after the onset of lactation. Colostrum intake is important for passive immunity, but also for the provision of carbohydrates, lipids, proteins, minerals and vitamins. In addition, colostrum contains hormones, growth factors, cytokines, enzymes, polyamines and nucleotides, which in the neonatal calf can exert biological effects. Thus, insulin-like growth factor I, which in colostrum is present in high amounts, may enhance gastrointestinal tract development and function of neonatal calves. Colostrum should be ingested as soon as possible after birth for efficient and sufficient absorption not only of immunoglobulins, but apparently also of (essential and non-essential) fatty acids and fat-soluble vitamins (β-carotene, retinol and α-tocopherol). The pattern of essential amino acids and the glutamine/glutamate ratio in blood plasma also greatly depend on whether and when colostrum is fed. In addition, there are considerable effects on hormones (especially on concentrations of insulin, glucagon, insulin-like growth factor-I, including its binding proteins, and cortisol) that are dependent on time and amount of colostrum fed.
The effects of feeding different amounts of colostrum or only milk replacer and the effects of Long-R3-IGF-I (administered s.c. or orally; 50 microg/[kg BW x d] for 7 d), and of s.c. injected recombinant bovine GH (rbGH; 1 mg/[kg BW x d] for 7 d) on small intestinal mucosal morphology in newborn calves were studied by histomorphometry. Neonatal calves fed colostrum six times exhibited greater (P < .01) villus circumferences, areas, and heights in total small intestine and especially in the duodenum than calves fed only milk replacer. Furthermore, villus circumferences and areas in total small intestine were greater (P < .05) in calves fed colostrum once than in calves fed no colostrum. Villus size in total small intestine was smaller (P < .05) in rbGH-treated than in control calves; jejunum villus circumferences and heights were especially reduced (P < .05). Crypt depths in ileum were greater (P < .05) in rbGH-treated calves. In conclusion, prolonged colostrum supply significantly enhanced small intestinal villus size in neonatal calves. In contrast, Long-R3-IGF-I had no significant influence on small intestinal morphology, and rbGH in supraphysiological amounts even reduced small intestinal mucosal variables after 1 wk of treatment. The study demonstrated enhanced postnatal development of the gastrointestinal tract by prolonged colostrum feeding, but not by Long-R3-IGF-I or GH.