Bovine Colostrum and Its Potential for Human Health and Nutrition

Abstract

Colostrum is the first milk produced post-partum by mammals and is compositionally distinct from mature milk. Bovine colostrum has a long history of consumption by humans, and there have been a number of studies investigating its potential for applications in human nutrition and health. Extensive characterization of the constituent fractions has identified a wealth of potentially bioactive molecules, their potential for shaping neonatal development, and the potential for their application beyond the neonatal period. Proteins, fats, glycans, minerals, and vitamins are abundant in colostrum, and advances in dairy processing technologies have enabled the advancement of bovine colostrum from relative limitations of a fresh and unprocessed food to a variety of potential applications. In these forms, clinical studies have examined bovine colostrum as having the substantial potential to improve human health. This review discusses the macro-and micronutrient composition of colostrum as well as describing well-characterized bioactives found in bovine colostrum and their potential for human health. Current gaps in knowledge are also identified and future directions are considered in order to elevate the potential for bovine colostrum as a component of a healthy diet for a variety of relevant human populations.

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REVIEW
published: 21 June 2021
doi: 10.3389/fnut.2021.651721
Frontiers in Nutrition | www.frontiersin.org 1June 2021 | Volume 8 | Article 651721
Edited by:
Nicole Clemence Roy,
University of Otago, New Zealand
Reviewed by:
Isabelle Le Huërou-Luron,
INRA Centre
Bretagne-Normandie, France
Louise M. Arildsen Jakobsen,
Aarhus University, Denmark
*Correspondence:
Sercan Karav
sercankarav@comu.edu.tr
Specialty section:
This article was submitted to
Nutrition and Metabolism,
a section of the journal
Frontiers in Nutrition
Received: 10 January 2021
Accepted: 27 May 2021
Published: 21 June 2021
Citation:
Arslan A, Kaplan M, Duman H,
Bayraktar A, Ertürk M, Henrick BM,
Frese SA and Karav S (2021) Bovine
Colostrum and Its Potential for Human
Health and Nutrition.
Front. Nutr. 8:651721.
doi: 10.3389/fnut.2021.651721
Bovine Colostrum and Its Potential
for Human Health and Nutrition
Ay ¸senur Arslan 1, Merve Kaplan 1, Hatice Duman 1, Ay ¸se Bayraktar 1,2 , Melih Ertürk 2,
Bethany M. Henrick 3,4 , Steven A. Frese 4,5 and Sercan Karav 1
*
1Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey, 2Uluova Dairy,
Canakkale, Turkey, 3Evolve Biosystems, Inc. Davis, CA, United States, 4Department of Food Science and Technology,
University of Nebraska Lincoln, Lincoln, NE, United States, 5Department of Nutrition, University of Nevada Reno, Reno,
NV, United States
Colostrum is the first milk produced post-partum by mammals and is compositionally
distinct from mature milk. Bovine colostrum has a long history of consumption by
humans, and there have been a number of studies investigating its potential for
applications in human nutrition and health. Extensive characterization of the constituent
fractions has identified a wealth of potentially bioactive molecules, their potential
for shaping neonatal development, and the potential for their application beyond
the neonatal period. Proteins, fats, glycans, minerals, and vitamins are abundant
in colostrum, and advances in dairy processing technologies have enabled the
advancement of bovine colostrum from relative limitations of a fresh and unprocessed
food to a variety of potential applications. In these forms, clinical studies have examined
bovine colostrum as having the substantial potential to improve human health. This review
discusses the macro-and micronutrient composition of colostrum as well as describing
well-characterized bioactives found in bovine colostrum and their potential for human
health. Current gaps in knowledge are also identified and future directions are considered
in order to elevate the potential for bovine colostrum as a component of a healthy diet
for a variety of relevant human populations.
Keywords: bovine colostrum, human health, bioactive proteins, oligosaccharides, infants
INTRODUCTION
Colostrum is the earliest milk produced from the mammary glands for the first few days
after giving birth and is unique in its composition of essential nutrients, immune factors, and
oligosaccharides that benefit the newborn (1,2). In the case of cows, bovine colostrum is produced
immediately after calving and quickly wanes to mature milk (3), which lacks the high level of
beneficial nutrients found in bovine colostrum. There are several factors affecting the composition
and physical properties of colostrum such as individuality, breed, parity, pre-partum nutrition,
length of the dry period of cows, and time post-partum (4). Generally, colostrum has more fat,
protein, peptides, non-protein nitrogen, ash, vitamins and minerals, hormones, growth factors,
cytokines, nucleotides, and less lactose compared to mature milk content. The concentration of
these compounds decreases rapidly in the first 3 days of lactation with the exception of lactose
content (5–7).

Arslan et al. Bovine Colostrum for Health, Nutrition
While the consumption of human colostrum by infants has
long been recognized as a source of critical bioactive proteins
for infants (8), the consumption of animal colostrum is also
practiced in many locations beyond the neonatal period (9,10).
In these cultures and regions, colostrum has long been consumed
as a health food or for medicinal purposes, with cultural
practices centered on the belief that animal colostrum was an
important component of the development of healthy children
and supportive of healthy or infirmed adults (9,11,12). While
these cultural or regional beliefs are associated with this practice,
the abundance of well-characterized bioactive compounds and
selective prebiotic components of this food may further support
this cultural knowledge from a scientific perspective.
Historically, liquid fresh colostrum was primarily consumed,
but pasteurized colostrum is also commercially available as a
standalone drink, though production remains small (13). In
European cultures and elsewhere such as India, and Scandinavia,
colostrum is also used in the production of cheeses and other
traditional foods (14). More recently, dried colostrum is collected
and processed as a dietary supplement, which is widely consumed
for perceived health benefits (10). In the US and EU, colostrum
supplements are marketed for a variety of health benefits,
including boosting immunity and gastrointestinal (GI) health.
While attractive in concept, there are limitations to this use of
dried colostrum, which are typically in a pill or tablet form, given
the limited amount of colostrum consumed relative to clinically
studied consumption rates.
Still, colostrum is a complex biological fluid and contains
significant components which are natural anti-microbial factors
for stimulating the maturation of calf immunity (15). In addition,
the development and function of the GI tract are shaped by
colostrum intake (5,6,16–18), and it also affects the metabolic
and endocrine systems as well as the nutritional state of neonatal
calves (5,6,17). Colostrum has muscular-skeletal repair and
growth potential in addition to its immune support function
and many benefits to health because of its content of bioactive
proteins (19). Further, some evidence suggests that the cytokines,
immunoglobulins, growth factors, antimicrobial compounds,
and maternal immune cells are transferred to the newborn with
the feeding of colostrum to support neonatal immunity (20–22).
Bovine colostrum has even been purported to treat viral and
bacterial infections as a nutraceutical (23). Together, the existing
evidence in support of colostrum suggests that there is potential
for colostrum to have a significant role in supporting human
health as well. While there are other studies which have begun
to look at colostrum from other animals (24–27), this review
explores the current knowledge on the bovine colostrum in the
context of nutrition, its bioactive components, and its potential
for human health and nutrition.
Bovine Colostrum Composition
Milk composition changes dramatically over the course
of lactation and bovine colostrum is compositionally and
nutritionally distinct from mature milk (28). In contrast
to mature milk, colostrum has a much higher protein and
moderately higher fat content, with substantially less lactose
(Table 1). This reflects the needs of the developing calf, where the
passive transfer of immunoglobulins is critical for health (41).
Further, as the volume of milk production increases over
lactation, there is a concomitant decrease in the mineral content
of milk (Table 1). Thus, colostrum represents a relatively high-
protein and lower-carbohydrate solution that can be processed
similarly to mature milk in order to reduce fat content and
shape the caloric density for desired nutritional applications.
Further, milk proteins are considered a “complete protein”
source owing to their amino acid profile, and high protein
digestibility, especially of whey proteins (42), though colostrum
contains higher concentrations of immunoglobulins which are
less digestible (Table 1).
While current dietary recommendations of protein intake
for a healthy adult with minimal physical activity are 0.8 g
per kg per day (43,44), a growing body of evidence suggests
that optimal intake may be higher [1.2–1.6 g per kg per day;
(45–47)] and this intake should be balanced across meals to
promote skeletal muscle protein synthesis (48). Especially in
elderly populations, optimal protein intake to reduce skeletal
muscle loss associated with aging is often not achieved, which
is further compounded by diminished proteolytic activity
associated with aging (49). Thus, colostrum may offer an
attractive digestible, complete protein source that can be
integrated into a calorically-appropriate diet. In addition to
macronutrients, bovine colostrum includes vitamins, minerals,
and a broad assortment of protein-derived bioactives which may
offer additive benefits to its macronutrient profile.
Main Factors Affecting Colostrum Composition
The composition and quality of the bovine colostrum are highly
variable due to genetic and environmental factors including
individuality, breed, parity, the timing of milking, diseases, pre-
partum nutrition, season, length of the dry period of cows, and
time post-partum (50–52).
Individual Variation Among Animals
Bovine colostrum quality is different among individuals
and between genetic backgrounds (31). For instance, the
concentration of immunoglobulin G (IgG) in bovine colostrum
and the volume of first milking vary among individual cattle
(53,54). The Jersey cows produce the highest (66.5 g/L) whereas
Friesian-Holsteins produce the lowest (41.2 g/L) concentrations
of IgG among breeds studied (55). In the case of cow parity,
first-calf heifers produce a lower yield of colostrum and lower
IgG concentration in colostrum than those cows in their second
or greater lactation. The quality of bovine colostrum increases
with parity after the second calving, and older cows generally
produce the best quality colostrum (54).
Another individual factor is the disease which influences
bovine colostrum quality. For instance, mastitis is an
inflammation of the mammary gland of the bovine that has
negative consequences including low quality of the colostrum.
The volume and concentration of bovine colostrum IgG are
lower in cows with infected mammary glands than cows with
uninfected glands (56). The age of cows also affects the quality
of colostrum. Some studies’ data are in general agreement that
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Arslan et al. Bovine Colostrum for Health, Nutrition
TABLE 1 | Bovine colostrum and mature milk composition.
Colostrum component naMean Minimum Maximum SE Mature milk
Bovine colostrum
Fat mg/mL 1,226 (29) 64.00 41.00 83.00 33.20 39.00 (28)
54 (30) 67.00 20.00 265.00 41.60
Protein mg/mL 1,226 (29) 140.00 116.00 166.00 36.70 36.00 (28)
55 (30) 149.20 71.00 226.00 33.20
Casein mg/mL – (31) 43.00 – – – 25.00 (31)
Whey mg/mL – (31) 120.00 – – – 5.10 (31)
Lactose mg/mL 1,226 (29) 27.00 23.00 31.00 5.50 49.00 (28)
55 (30) 24.90 12.00 52.00 6.50
Dry matter mg/mL 55 (30) 276.40 183.00 433.00 58.40 125.00 (28)
Ash mg/mL 55 (30) 0.50 0.20 0.70 0.10 7.00 (28)
IgG mg/mL 1,239 (29) 55.00 38.10 67.80 25.75 0.257 (32)
IgA mg/mL 55 (30) 1.66 0.50 4.40 0.50 0.04–0.06 (12,30,33,34)
IgM mg/mL 55 (30) 4.32 1.10 21.00 1.10 0.03–0.06 (12,30,33,35)
Oligosaccharides mg/mL – (36) – 0.70 1.20 – 0.3–0.5 (36)
Lactoferrin mg/mL 55 (37) 0.82 0.10 2.20 0.10 0.10–0.30 (37)
Lactoperoxidase mg/mL – (38) – 11.00 45.00 – 13–30 (38)
Ca mg/kg 55 (30) 4,716.10 1,898.00 1,775.10 8,593.50 1,220.00 (39)
– (40) 1,518.60 – – –
P mg/kg 55 (30) 4,452.10 1,706.29 1,792.40 8,593.5 1,520.00 (39)
– (40) 1586.00 – – –
Mg mg/kg 55 (30) 733.24 286.07 230.30 1,399.60 120.00 (39)
– (40) 219.70 – – –
Na mg/kg 55 (30) 1,058.93 526.02 329.70 2,967.80 580.00 (39)
– (40) 516.70 – – –
K mg/kg 55 (30) 2,845.89 1,159.89 983.20 5,511.40 1,520.00 (39)
– (40) 1,297.50 – – –
Zn mg/kg 55 (30) 38.10 15.90 11.20 83.60 5.30 (39)
– (40) 151.00 – – –
Fe mg/kg 55 (30) 5.33 3.09 1.70 17.50 0.80 (39)
34.66 – – –
Mnbmg/kg 23 (30) 0.10 0.11 0.00 0.36 0.20 (39)
– (40) 2.62 – – –
Vitamin A mg/kg 55 (30) 4.90 1.82 1.40 19.30 460.00 (39)
Vitamin E mg/kg of fat 55 (30) 77.17 33.52 24.20 177.90 2.10 (39)
Vitamin B12 µg/mL 5 (30) 0.60 0.35 0.20 1.10 4.50 (39)
aNumber of colostrum samples reported in the referenced study.
bPart of the samples were quantified as <0.05 and therefore not included in averages.
older cows have a higher quality of colostrum than younger cows
(53,54,57). The association between older age and good quality
of colostrum is thought to be a result of increased pathogen
exposure, improved immunity, and body condition score (31).
Environmental Factors
The timing of the bovine colostrum milking after parturition
has significant effects on concentrations of IgG in the
bovine colostrum. Early or immediate colostrum milking will
significantly increase colostrum quality. Moore et al. (58)
reported that colostrum collected 6, 10, and 14 h after parturition
has lower IgG concentration than colostrum collected 2 h after
parturition. Another study also showed that bovine colostrum
quality is highest immediately after parturition of North
American herds, but it decreased when milking was delayed
(53,58). Bovine colostrum quality is also affected by the calving
season. Cows calving during the summer months have lower
quality colostrum than those calving in the autumn months (53).
The bovine colostrum fat percentage is at 24 and 48 h after birth
is affected by the calving season. Animals born in autumn-winter
seasons have a higher colostrum fat percentage than those in
calving in spring-summer seasons. One cause may be differences
in metabolism, feed, and water consumption in different seasons
(59,60).
The dry period length is an important period for cows which
lasts ∼6–8 weeks. This period is needed for the renewal of
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Arslan et al. Bovine Colostrum for Health, Nutrition
milk secretion tissue, preparation for lactation, and completion
of fetus development (61–63). Colostrum starts to be secreted
in the last 15–20 days of the dry period and its composition
changes continued until parturition (62,64). Le Cozler et al. (65)
also reported that there is a positive coefficient of correlation
(R2=0.22; P<0.01) between IgG concentration and dry period
length (65).
Fats
Colostrum contains a higher percentage of fat than mature
milk (66) and the composition of these fats is also distinct.
O’Callaghan et al. (67) examined the composition of colostrum
and the changes observed during the transition to mature milk,
reporting that colostrum is higher in palmitic, palmitoleic, and
myristic acids, relative to mature milk (67). While these fat
profiles are well-suited to the developing calf (68), the profiles
of these fats and the higher concentration of saturated fat have
been associated with long-term negative health outcomes, though
there is some disagreement within the literature as to the level of
support for the role of dairy fats in cardiovascular disease (69).
There is evidence that these fatty acids play a role as signaling
molecules and, as dietary fatty acids, contribute to the regulation
of lipogenesis in the liver (70). Further, many vitamins found in
milk are fat soluble (e.g., vitamin A, D) and removal of these fats
also reduces the concentration of these vitamins in colostrum.
It is of relevance to consumers that the advances in dairy
technology which enable efficient separation of fats from the
aqueous fraction of milk (that is, the fraction which contains
proteins, carbohydrates, minerals, and some vitamins) enable
the reduction or removal of these fats from colostrum, ahead
of downstream processing, making the potential for a low-fat
or fat-free colostrum product possible. However, some have
speculated that the tradeoff between dairy fats and the removal of
bioactive found in the fat fraction of dairy foods may not always
be a net benefit (69). To resolve this conflict in the literature,
it is clear that well-controlled clinical studies investigating the
relationship between the dietary fats found in colostrum and
health are needed.
Vitamins/Minerals Found in Colostrum
Bovine colostrum contains also high levels of fat-soluble and
water-soluble vitamins that are critical to human health (4).
Notably, vitamin A is reported to be found at high concentrations
in colostrum in a variety of forms including retinol, retinal,
retinoic acid, retinyl esters and as provitamin A carotenoids
(71–73). Vitamin E, in the form of tocopherols and tocotrienols
(∼mean 77.17 mg/kg) are found in low density lipoproteins
in colostrum (4,30). Vitamin K is also found in greater
concentration in colostrum compared to mature milk in two
forms, phylloquinone, and menaquinones (71). Vitamin D is
found in higher concentrations in colostrum than mature milk
(74). Vitamin D has important roles in immune activities and
promotes the uptake of calcium and phosphorus in the small
intestine (75). It has two major forms as cholecalciferol (vitamin
D3) and ergocalciferol (vitamin D2) and their concentration
decreases from 1.2 to 0.36 IU. g−1 during the first 5 days post-
partum (76). Vitamin C and the B vitamins are also found in
the water-soluble fraction of colostrum at a higher concentration
compared to mature milk (77) and together provide a natural
source of essential vitamins critical to human health.
Bovine colostrum and mature milk are known to be good
sources of several minerals especially calcium and phosphorus
(75). Recent studies revealed that the mean concentrations of
several important minerals in colostrum are significantly higher
than in mature bovine milk. Calcium is necessary for the
maintenance of calf development and their healthy bones and
teeth. Phosphorus is also crucial for the metabolic rate and
physiological functions including development of skeletal tissue,
energy utilization, protein synthesis, and transport of fatty acids
(78). Magnesium is present in a relatively large amount, along
with zinc and selenium in bovine colostrum (75).
Bioactive Proteins
Immunoglobulins (Igs)
Immunoglobulins (Igs) are complex proteins, known as
antibodies, that make up a significant part of the total protein in
bovine colostrum. The immunoglobulins in bovine colostrum
mainly come in 3 different varieties called isotypes including IgG
(IgG1 and IgG2), IgA, IgM. IgG is the dominant immunoglobulin
in bovine colostrum, which makes up 85–90% of the total
immunoglobulin content. IgG1 represents 80–90% of the total
IgG content in bovine colostrum, followed by IgM, IgA, and IgG2
(23,79,80). These immunoglobulins are essential in the survival
of the calves and their immune systems and they neutralize
enteric pathogens such as bacteria, microbes, and viruses. Using
bovine colostrum as a source of antibody preparations to support
bovine and human health is an important research subject that
has been studied for decades (81).
One of the key differences between mature milk and
colostrum is the high concentration of IgG found in colostrum,
which reaches up to 50–100 mg/mL in the first days after birth
(33,82,83). Bovine serum IgG1 and IgG2 concentration decrease
before parturition, they are transferred from the blood into the
colostrum. In fact, nearly all IgG in colostrum is transferred from
bovine serum into the colostrum and milk (84,85).
The high concentration of IgG is necessary for the survival of
calves, which is strongly dependent on the transfer of IgG from
bovine colostrum to calves to provide passive immunity as cows
cannot transfer IgG through the placenta (86). Indeed, if calves
do not receive colostrum immediately after birth, they are prone
to infection and will suffer from a higher risk of morbidity and
mortality (31,87,88).
Lactoferrin
Lactoferrin is a cationic, iron-binding glycoprotein present
as about 0.80 mg/mL in bovine colostrum (37). It has
multiple functions including antibacterial, antifungal,
antiviral, antiparasitic, antitumor and immunomodulatory
(anti-inflammatory) effects (23,35,89,90), and is the major
protein in the milk serum of all mammals (91). Bovine
colostrum-derived lactoferrin has antimicrobial activity by
inhibiting the growth of disease-causing protozoa, yeasts,
bacteria, and viruses, and lactoferrin may prevent the attachment
of pathogens to epithelial cells and help maintain intestinal
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Arslan et al. Bovine Colostrum for Health, Nutrition
permeability and stability (83,92,93). Moreover, there are some
studies showing that bovine colostrum-derived lactoferrin can
increase the proliferation of cells involved in the bone formation
such as osteoblasts, and the release of some growth factors from
osteoblasts (94,95).
Furthermore, it is known to play a role in iron uptake in the
intestine and activation of phagocytes and immune responses.
Receptors for lactoferrin are expressed on intestinal tissue,
monocytes, macrophages, neutrophils, lymphocytes, platelets,
and on some bacteria (96). Bovine lactoferrin supplements are
thought to support the immune system and influence immune
cell activity potentially via these antioxidant, antibacterial, and
antiviral properties (97). The greatest concentration of this
protein is found in colostrum, which has been determined to be
four times greater than mature milk (98).
Lactoperoxidase
Lactoperoxidase is a major antibacterial enzyme found in
bovine colostrum, it is a basic glycoprotein that catalyzes
the oxidation of thiocyanate and generates intermediate
compounds with antimicrobial activities (99). The concentration
of lactoperoxidase is 11–45 mg/L in bovine colostrum and
13–30 mg/L in mature bovine milk (38). Its concentration in
bovine colostrum is low initially, but it reaches the maximum
level within 3–5 days after parturition. Lactoperoxidase catalase
activity is also higher in bovine colostrum than in mature milk
(100,101).
Lactoperoxidase activity produces toxic oxidation products
that inhibit bacterial metabolism by oxidation of essential
sulfhydryl groups in proteins. This system is toxic to some gram-
positive and negative bacteria like Pseudomonas aeruginosa,
Salmonella typhimurium,Listeria monocytogenes,Streptococcus
mutans, and Staphylococcus aureus (102). The lactoperoxidase
system also inactivates the poliovirus, vaccinia virus, and HIV
(93,103,104).
Oligosaccharides
Bovine colostrum is a rich source of complex and highly
selective oligosaccharides and glycans. The concentration of
oligosaccharides in colostrum is 0.7–1.2 mg/mL and the
majority of these structures are acidic oligosaccharides which
are lower in mature bovine milk (36,105). Forty distinct
oligosaccharides compositions have been detected in bovine
colostrum so far (106–108). The total colostrum oligosaccharides
differ between cows because of their genetic variability (109).
Predominant oligosaccharides in bovine colostrum are 3′
sialyllactose (3′SL), 6′sialyllactose (6′SL), 6′siayllactosamine
(6′SLN) and disialyllactose (DSL). 3’SL is 70% of total
oligosaccharide content in bovine colostrum (105,107,110,
111). 3′SL, 6′SL, and 6′SLN levels in colostrum were highest
following parturition and decreased by 48 h post-partum, while
neutral oligosaccharide level increased (105). Breed specific
differences have also been identified in oligosaccharide content.
Concentrations of 3′SL, 6′SL, 6′SLN and DSL were found as
867, 136, 220, and 283 µg/mL, respectively, in colostrum from
Jersey cows, while these concentrations were 681, 243, 239, and
201 µg/mL, respectively, in Holstein colostrum after parturition
(112). Both free oligosaccharides (bovine milk oligosaccharides,
BMOs) and complex, conjugated N-glycans represent the
majority of the prebiotic components of bovine colostrum (113).
While there are many distinctions between BMOs and human
milk oligosaccharides (HMOs), there has been significant interest
in utilizing milk and colostrum as a source of BMOs for human
nutrition and health to modulate the GI microbiome (114).
In contrast to HMOs, BMOs are predominantly sialylated (i.e.,
acidic) oligosaccharides, with a low propensity for fucosylation
(106) and a lower structural diversity (106). Recent advancements
in enzymatic glycosylation have provided opportunities for the
structural enhancement of BMOs to alter their structure to
resemble HMOs (115). Several complexities in milk processing
have thus far limited the ability of BMOs to be separated
from lactose found at high concentrations in milk (114),
though solutions have begun to emerge (116) which complicates
their utility for human nutrition and health. Further, though
pilot experiments with purified BMOs in adults have not yet
demonstrated generalizable changes to GI microbial populations
(117), future work in infants may be more promising as recent in
vitro experiments with BMOs are more promising (118,119).
Complex and hybrid N-glycans found in bovine mature milk
and colostrum may also provide a source of prebiotic glycans that
can be selectively utilized in a fashion similar to HMOs/BMOs
(120). Further, the conjugation of these N-glycans to milk
proteins enable different strategies for their recovery. Protein
separation from lactose and subsequent treatment to separate
N-glycans from their protein conjugates may offer a potentially
attractive avenue to purification of these glycans (121). Thus, N-
glycans derived from bovine colostrum, which is exceptionally
rich in N-glycosylated proteins (122), may be a potent source
of bioactive glycans to serve as prebiotic substrates. Extensive
characterization of complex N-glycans derived from bovine
milk proteins abundant in colostrum now shows that these N-
glycans are highly selective for certain bacteria in the adult GI
microbiome. The bacteria able to access these glycans are further
restricted, relative to larger repeated polymers of less complex
oligosaccharides which are limited to select Bifidobacterium
species (e.g., Bifidobacterium longum subsp. infantis). Some
strains of these species have been associated with diminished
enteric inflammation and improved GI barrier function in
humans (123,124). Bovine colostrum is also a potential source of
anti-infective glycans and recent work provides evidence for the
anti-infective activity of oligosaccharides sourced from bovine
colostrum against a highly invasive strain of C. jejuni (125).
CLINICAL APPLICATIONS OF BOVINE
COLOSTRUM
Body Composition and Exercise
Performance
The first study investigating the role of colostrum
supplementation in exercise performance was completed in
1997 and showed marked improvements on explosive muscle
power and increased concentration of immunoglobulins in
serum (35). This finding is relevant given intense physical
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Arslan et al. Bovine Colostrum for Health, Nutrition
activity can suppress immunity several hours after training
(126). Subsequent, well-controlled studies in comparison
to whey protein concentrate have demonstrated significant
improvements in lean body mass and weightlifting performance
(127), in athletic performance among male and female athletes
(128), speed in elite cyclists with dose-dependent effects (129),
and in runners for recovery (130). Duff et al. (131) indicated
that bovine colostrum supplementation (60 g/d of colostrum)
on male and female older adults during resistance training
is beneficial for increasing leg press strength and reducing
bone resorption in comparison to whey protein complex
supplementation. Improvement in the upper body strength,
muscle thickness, lean tissue mass, and cognitive function were
noted for colostrum supplemented group as well as whey protein
treated group (131).
Despite this progress, the exact mechanism behind these
marked improvements is not fully elucidated. As human studies
typically use whey protein with similar protein content, observed
differences are unlikely to simply be a response to protein
digestibility or amino acid supplementation. Given that bovine
colostrum immune components are likely not providing passive
immunity to the human, it is possible that bioactive compounds
and/or their metabolites have a direct effect on the immune
system (35,126,132–135). There is currently weak support for
the potential for bovine colostrum supplementation to improve
leukocyte function relating to adaptive immunity (126). While
a 33% increase in saliva IgA was noted after supplementation
of colostrum at 20 g/day for 2 weeks (134) and a 79%
increase in IgA in runners fed 12 g/day for 12 weeks was
reported (132), these results were not repeated in other studies
(35,135–140). Further, colostrum supplementation diminished
exercise-induced intestinal permeability which was replicated
in in vitro culture models of intestinal epithelial cells (141).
Considering the safety profile and generally positive past research
from well-controlled studies, further research is warranted
to understand the underlying mechanism and explain inter-
individual variations and unexplored discrepancies between the
growing number of studies on colostrum supplementation in
regards to body composition and athletic performance.
NSAIDs Induced GI Inflammation and
Permeability
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most
common prescribed medicine and used for the symptomatic
treatment of acute pain, chronic inflammatory, and degenerative
joint diseases (142,143). NSAIDs can cause gastric and intestinal
damage such as peptic ulceration and injury to both the small
and large intestine. Complications from NSAIDs use include
increased intestinal permeability with protein and blood loss,
and also stricture formation (142,144). Approximately 2% of
subjects taking NSAIDs experience adverse effects on the GI
tract including bleeding, perforation, and inflammation. Acid
suppressants and prostaglandin analogs are used to reduce gastric
injury induced by NSAIDs, but these are not adequately effective
in preventing small intestine injury. Hence, additional avenues
for the mitigation of these negative side effects are needed.
Some research suggests that colostrum may be an alternative,
owing to the composition of growth factors like α-IGF-1, β-
IGF-1, transforming growth factor (TGF), and epidermal growth
factors (EGF). These growth factors are capable of stimulating the
repair process of the GI tract (145) and are complementary to
evidence supporting diminished GI permeability associated with
exercise (141).
In a clinical examination of bovine colostrum for protection
against NSAID-induced enteropathy, seven male volunteers (26–
38 years old) who were taking NSAIDs or suffering from
conditions likely to affect intestinal permeability (e.g., coeliac
disease or previous intestinal surgery), were evaluated for the
potential of bovine colostrum to alter intestinal permeability with
concomitant indomethacin supplementation. In this crossover
study, following an initial baseline permeability assessment, these
volunteers were supplemented orally with 125 mL of bovine
colostrum or a whey placebo three times daily for seven days. At
the end of the trial period, intestinal permeability was reassessed
and a 2-week “washout” period was performed between the
crossover. Approximately a 3-fold increase in permeability was
observed in the participants taking the whey placebo with
indomethacin, while no significant increase in permeability was
seen in the participants taking co-administration of bovine
colostrum with indomethacin (146). In support of these findings,
molecular characterization of the mechanism underlying these
effects have been documented. Mir et al., (147) demonstrated
that bovine lactoferrin can act as a carrier for NSAIDs by
binding to these molecules, but with far lower affinity than
the protein targets for NSAIDs which suggests that the efficacy
of NSAIDs may not be affected by co-administration of a
lactoferrin-containing protein source, like bovine colostrum
(147). While further studies will be required to demonstrate that
these compounds, when co-administered with bovine colostrum,
maintain their desired efficacy, there is growing and consistent
evidence supporting the potential for the use of bovine colostrum
to manage the potential side effects of NSAIDs.
Uses of Bovine Colostrum in Specific
Clinical Populations
Bovine colostrum has led to human supplementation trials due
to potential for improvement of GI health and integrity. Several
conditions related to GI conditions associated with chronic
or acute infections have been investigated for the potential
of bovine colostrum to ameliorate symptoms associated with
these conditions or infections. While the mechanisms behind
these findings are difficult to disentangle given the disparate
populations and disease etiologies, there are consistent themes
related to the improvement of GI symptoms and reduced
inflammation associated with each, though not all conditions
demonstrate promising avenues for therapy.
Ulcerative Colitis
Ulcerative colitis, an inflammatory bowel disease associated
with durable inflammation and ulcers in the colon (148),
was investigated as a potential target for a bovine colostrum
enema treatment in a small proof-of-concept trial. The authors
rationalized this approach given the high concentrations of
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Arslan et al. Bovine Colostrum for Health, Nutrition
antimicrobial peptides, immunoglobulins and growth factors
found in colostrum (149). In this pilot study, fourteen patients
with active mild to moderate colitis were compared. Eight
patients received 100 mL (10% solution) of bovine colostrum
and six patients received an albumin placebo twice per day
for 4 weeks. Improvement of the symptom score including
patient well-being, abdominal pain, rectal bleeding, temperature,
anorexia/nausea, bowel frequency, stool consistency, abdominal
tenderness and the presence of extra-intestinal manifestations
was reported in seven of the eight patients in the bovine
colostrum treated groups (149). While this study is small, the
findings show a significant reduction in symptom scores and
follow up studies in a similar population with a larger sample size
may be warranted.
Necrotizing Enterocolitis
Necrotizing enterocolisis (NEC) is one of the most common
morbidities associated with preterm birth, and among the
chief causes of mortality among infants born preterm (150).
Several studies have examined the impact of either human or
bovine-derived colostrum on NEC outcomes and development
of preterm infants. In one clinical trial of 86 low birthweight
infants supplemented with bovine colostrum in a dose of 2 g,
four times per day for infants between 1,000 and 1,500 g and
1.2 g, four times per day for those under 1,000 g at birth. No
significant differences were observed in the occurrence of NEC,
sepsis, or mortality after the administration of bovine colostrum
as compared with placebo (151). In a meta-analysis examining
the use of bovine and human colostrum among preterm infants,
Sadeghirad et al. concluded that the cumulative findings in the
literature suggest that neither human nor bovine colostrum had
an effect on the incidence of severe NEC, mortality, culture-
proven sepsis, feed intolerance, or length (152). The lack of effects
is observed on NEC patients due to some limitations such as
using commercial bovine colostrum supplement and number
of patients is modest (146,147). Given these findings, it will
be difficult to rationalize continued use of bovine or human
colostrum with preterm infants for improvements in these
outcomes. However, the use of human colostrum in preterm
infants should not be curtailed based on these outcomes as other
benefits have been demonstrated for preterm infants (153).
Traveler’s Diarrhea
Acute infection with enterotoxigenic Escherichia coli (ETEC)
represents the most common causes of so-called Traveler’s
Diarrhea, associated with travel to tropic and semitropical
regions throughout the world (154). As bovine colostrum plays
a key role in protecting the neonatal calf from environmental
pathogens via passive immunity and ETEC represents one
of the primary causative agents of neonatal calf diarrhea
(155), researchers have been interested in determining whether
the same effects can be demonstrated in humans at risk of
Traveler’s Diarrhea.
Using hyperimmune bovine colostrum which is rich in
immunoglobulins targeting 14 strains of ETEC, the efficacy and
dose response of consuming bovine colostrum in a tablet form
(400 mg of bovine colostrum protein) demonstrated a dose-
dependent and significant improvement in protecting against
the development of diarrhea among volunteers in a double
blinded, placebo-controlled ETEC challenge study. A 400 mg
serving of hyperimmune bovine colostrum protein administered
with a bicarbonate buffer three times daily conferred 90.9%
protection when compared to the placebo (156). Bicarbonate
buffer contributes to the enhancement the protective effects
of hyperimmune colostrum protein in the ETEC challenge
experiments, but the difference was not statistically significant.
As little as 200 mg consumed three times per day without buffer
gave an estimated 58.3% protection from diarrhea symptoms,
compared to the placebo group (156).
In addition to ETEC, viruses contribute to a significant
proportion of both neonatal calf diarrhea and Traveler’s Diarrhea
(154,155). In a double blinded, placebo-controlled study, Mitra
et al., (157) reported that consuming three daily servings of
100 mL of hyperimmune bovine colostrum targeting human
rotavirus for 3 days conferred a modest but significant reduction
in both the duration of diarrhea and the total stool output among
male infants 6–24 months of age (157). Similarly, another study
reported that purified immunoglobulins from hyperimmune
bovine colostrum conferred a similar effect in acute rotavirus
infection, supporting these findings (158).
While neither study examined the impact of colostrum
from cows which had not been immunized against the target
pathogen, a clinical trial examining the differences between
hyperimmune bovine colostrum and bovine colostrum among
children infected with shigellosis caused by Shigella dysenteriae
(S. dysenteriae) failed to find any improvements among patients
relative to the concurrent antibiotic therapy. However, preclinical
studies in other biomedical models (e.g., gnotobiotic pigs)
have shown promise for hyperimmune bovine colostrum in
preventing diarrhea caused by Clostridioides difficile (C. difficile).
Together, these findings may suggest that infectious mechanisms
of pathogenesis shape the ability of hyperimmune bovine
colostrum to influence disease progression as S. dysenteriae
invades epithelial cells (159), potentially evading hyperimmune
bovine colostrum immunoglobulins, while ETEC and C. difficile
utilize secreted toxins to induce epithelial damage (160,161).
FUTURE DIRECTIONS
Given the biological role of colostrum for neonates (8,162),
its documented bioactive components as outlined here, and the
potential for development as a functional food or food ingredient.
There is a significant interest in developing colostrum as an
ingredient to improve the bioactivity of foods and/or their
potential health benefits. With a higher protein content and
lower lactose concentration, this favorable protein/carbohydrate
ratio is also nutritionally attractive and the potential for the
future development of the ingredients and constituent fractions
of colostrum is promising. However, overcoming processing
challenges to separate bioactive fractions from colostrum remains
a challenge to both study the mechanisms by which this fluid can
act on humans and for practical product development. Future
Frontiers in Nutrition | www.frontiersin.org 7June 2021 | Volume 8 | Article 651721

Arslan et al. Bovine Colostrum for Health, Nutrition
clinical trials should address current gaps in understanding which
populations, such as those with GI disorders, may benefit most
from colostrum consumption and whether whole or fractionated
colostrum offers the most attractive balance of nutrition and
bioactive properties.
AUTHOR CONTRIBUTIONS
SK organized the general content of the paper. AA was
responsible for general editing and organizing the authors and
also responsible for the two sections of the paper. MK contributed
one section of the paper. HD was responsible for writing one
section of the paper. AB was responsible for the one section of
the paper. ME contributed to a section of the paper. BMH was
responsible for the organizing a section. SAF contributed editing
and organizing the paper. All authors contributed to the article
and approved the submitted version.
ACKNOWLEDGMENTS
Uluova Süt Ticaret A.¸S (Uluova Milk Trading Co.) is funding to
achievement of this study.
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Conflict of Interest: BMH is an employee of Evolve Biosystems, Inc. SK has
received funding from Uluova Süt Ticaret A.¸S (Uluova Milk Trading Co.), a
company focused on the production of colostrum and lactoferrin. ME and AB are
employees of Uluova Dairy.
The remaining authors declare that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential
conflict of interest.
Copyright © 2021 Arslan, Kaplan, Duman, Bayraktar, Ertürk, Henrick, Frese and
Karav. This is an open-access article distributed under the terms of the Creative
Commons Attribution License (CC BY). The use, distribution or reproduction in
other forums is permitted, provided the original author(s) and the copyright owner(s)
are credited and that the original publication in this journal is cited, in accordance
with accepted academic practice. No use, distribution or reproduction is permitted
which does not comply with these terms.
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