Nutrition

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Special Article
Clinical applications of bovine colostrum therapy:

a systematic review
Mathias Rathe, Klaus Müller, Per Torp Sangild, and Steffen Husby
Bovine colostrum, the first milk that cows produce after parturition, contains high
levels of growth factors and immunomodulatory components. Some healthy and
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diseased individuals may gain health benefits by consuming bovine colostrum as a
food supplement. This review provides a systematic, critical evaluation of the current
state of knowledge in this area. Fifty-one eligible studies were identified from the
following databases: Medline, Embase, Global Health, the Cochrane Library, and the
Cumulative Index to Nursing and Allied Health Literature. Studies were heteroge-
neous with regard to populations, outcomes, and methodological quality, as judged
by the Jadad assessment tool. Many studies used surrogate markers to study the
effects of bovine colostrum. Studies suggesting clinical benefits of colostrum supple-
mentation were generally of poor methodological quality, and results could not be
confirmed by other investigators. Bovine colostrum may provide gastrointestinal and
immunological benefits, but further studies are required before recommendations
can be made for clinical application. Animal models may help researchers to better
understand the mechanisms of bovine colostrum supplementation, the dosage regi-
mens required to obtain clinical benefits, and the optimal methods for testing these
effects in humans.
© 2014 International Life Sciences Institute
INTRODUCTION Antimicrobial, immunomodulatory, and

growth-stimulating factors in bovine colostrum
Colostrum is the first milk that mammals produce after
parturition, and its composition differs markedly from Bovine colostrum may have direct antimicrobial and
that of milk produced later in lactation. This fluid has endotoxin-neutralizing effects throughout the alimentary
evolved under selective pressure to care for highly sensi- tract as well as other bioactivities that suppress gut
tive mammalian neonates and is believed to contribute inflammation and promote mucosal integrity and tissue
significantly to initial immunological defense in the neo- repair under various conditions related to tissue injury.
natal period as well as to the growth, development, matu- Constituents of bovine colostrum may not only have local
ration, and integrity of the neonatal gastrointestinal (GI) effects but may also contribute to immunological events,
tract. Certain effects of colostrum may be species specific, resulting in systemic effects after contact with the gut
whereas other effects may be shared across species.1,2 mucosa. Bovine colostrum contains numerous factors
Hence, the unique nutritional and biological activities of attributable to the acquired and innate immune systems,
bovine colostrum that benefit neonatal calves may also including a range of peptides and proteins with direct
benefit specific groups of humans. antimicrobial effects.3
Affiliations: M Rathe and S Husby are with the Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark.
K Müller is with the Pediatric Clinic and Institute of Inflammation Research, Rigshospitalet, Copenhagen, Denmark. PT Sangild is with the
Clinical and Experimental Nutrition, University of Copenhagen, Faculty of Science, Frederiksberg, Denmark.
Correspondence: M Rathe, Hans Christian Andersen Children’s Hospital, Odense University Hospital, Sdr. Boulevard 29, Odense C DK-5000,
Denmark. E-mail: [email protected]. Phone: +45-30296665.
Key words: bovine colostrum, dietary supplements, dietetics, gastrointestinal tract, nutrition
doi:10.1111/nure.12089
Nutrition Reviews® Vol. 72(4):237–254 237
In contrast to maternal immunoglobulin in humans, contains vascular endothelial and basic fibroblast growth
which is transferred across the placenta to the fetus, factors.12 Platelet-derived growth factor, also present in
maternal immunoglobulin in cattle does not cross the bovine colostrum, is believed to be an important mitogen
placenta. Thus, the newborn calf is dependent on the for fibroblasts and to serve in wound healing. Transform-
intestinal absorption of immunoglobulin, which is ing growth factor-β, which is present in high concentra-
present in large quantities in bovine colostrum and pro- tions in colostrum, has anti-inflammatory effects, and
vides passive immunity after birth.4 Immunoglobulin regulates proliferation, differentiation, and repair in dif-
concentrations are nearly 100-fold higher in colostrum ferent tissues, is essential in the induction of regulatory T
than in mature milk and are critical for immunological cells. Transforming growth factor-α, on the other hand, is
defense in a calf ’s early days of life.5 a peptide involved in maintaining epithelial function and
Components of bovine colostrum attributable to the integrity.5,11
innate immune system include antimicrobial peptides, Although many of these compounds are considered

such as lactoferrin and lactoperoxidases, which have addi- labile and may be influenced by different dairy processes,
tive antibacterial effects.5 Lactoferrin is a glycoprotein they are present in standardized colostrum deriva-
with antibacterial as well as antiviral, lipopolysaccharide- tives,12,13 and evidence of the recovery and preserved
binding, and growth-regulating effects. Lactoperoxidase is bioactivity of bovine immunoglobulin after GI transit has
an antibacterial enzyme that inhibits bacterial metabolism been documented.14,15 However, the effects of more labile
and has been shown to be toxic to a range of gram-positive components like cytokines may be questionable, and
and gram-negative bacteria; it also possesses antiviral products of different origin, milking times, and formula-
activities.Lysozyme is a lytic enzyme that plays a role in the tion may fall under the general term of colostrum.
innate immune system by attacking peptidoglycan cell The aim of this review is to provide a complete evalu-
constituents found primarily in gram-positive bacteria, ation of the current state of knowledge and evidence
leading to bacterial lysis.5 regarding the effects of enteral supplementation with
Bovine colostrum contains a range of immune- bovine colostrum. In addition to presenting and discuss-
regulating and inflammatory cytokines, such as inter- ing previous research, this review highlights remaining
leukins (IL-1β, IL-2, IL-6, IL-17), tumor necrosis factor-α, challenges and possible future research areas. Other
interferon-γ, and other nonantimicrobial compounds that reviews of specific aspects of bovine colostrum supple-
contribute to the control of infection and inflammation mentation have been published,11,16–21 but this is the first
through cytokine-facilitated crosstalk, pathogen recogni- systematic review providing a comprehensive overview of
tion, and immune cell recruitment. In addition, specific the field.
microRNA with immune-regulating potential is present
in microvesicles,is stable under the degradative conditions METHODS
of the GI tract, and may have the potential to reach the
immune cells of gut-associated lymphoid tissues.6–8
Search strategy
Bioactive oligosaccharides may be important in protecting
against pathogens and promoting the growth of beneficial Electronic literature searches of the Medline PubMed
microflora in the colon.9 interface, Embase, Cochrane Library, Cumulative Index
Bovine colostrum has growth-promoting effects on to Nursing and Allied Health Literature (CINAHL), and
human intestinal tissue, probably attributable to the com- Global Health databases were conducted using the key
bination of several growth factors.10 The role of luminal words (colostrum OR colostrums) AND (bovine OR cow
growth factors in the healthy adult gut has not been estab- OR cows OR cattle) as MeSH terms and free text. Searches
lished, as the receptors for many trophic factors are not were limited to human trials published in English from
present luminally. However, these luminal ligands may be the date of database inception through March 6, 2013. An
able to reach target receptors on the basolateral mem- additional search of Medline records from the previous 6
branes of mucosal cells in the damaged gut, and detri- months (March 6, 2013–September 6, 2012) using iden-
mental gut conditions may result in the modification of tical terms without the human trial limitation was con-
receptor distribution to include apical membranes.11 ducted to account for any delay in key word assignment.
Colostrum contains high amounts of the insulin-like Bibliographies of the papers identified were scanned to
growth factors (IGFs) IGF-1 and IGF-2. These hormones identify additional relevant publications.
are heat and acid stable and are able to withstand dairy
processing and the degradative conditions of the GI tract. Inclusion and exclusion criteria
They facilitate cellular growth, differentiation, and devel-
opment and may have local effects or be absorbed into the Following the PRISMA statement,22 titles and abstracts of
circulation, mediating systemic effects. Bovine colostrum identified studies were reviewed using the following
238 Nutrition Reviews® Vol. 72(4):237–254

inclusion and exclusion criteria, according to the popula- (n = 4, 8%), Australia or New Zealand (n = 13, 25%), and
tion, intervention, comparison, and outcome format. Africa (n = 2, 4%). A total of 2,326 patients (range, 3–605
Abstracts, single case reports, and letters were not patients/trial; mean, n = 47.5; median, n = 29) were col-
included. Because bovine colostrum may have the capac- lectively enrolled. Table 1 provides an overview of the
ity to benefit a wide range of the population, all studies of included studies. Briefly, the analysis identified the fol-
its use as a dietary supplement (food, pill, powder, extract) lowing trial types: two double-blind, crossover, random-
in healthy and/or diseased humans were considered for ized trials (RTs) of nonsteroidal anti-inflammatory drug
inclusion. The use of a control group was not a criterion (NSAID)-induced GI toxicity, reported in one article26;
for inclusion. Studies using a single compound extracted five trials examining HIV-associated diarrhea and immu-
from bovine colostrum were not included. The analysis nosuppression, including one case series,27 three open-
was restricted to studies of standard or “natural” bovine label, uncontrolled, observational studies,28–30 and one
colostrum preparations and excluded studies of open-label, uncontrolled, randomized study31; two

hyperimmune bovine colostrum, which contains large placebo-controlled RTs investigating the effects of bovine
amounts of specific antibodies due to prior immunization colostrum supplementation on inflammatory responses
of cows with specific microorganisms. Any quantifiable and microbial translocation after surgery32,33; two double-
change in a health- or performance-related clinical or blind, placebo-controlled, crossover RTs investigating the
paraclinical parameter was accepted as an eligible effects of bovine colostrum supplementation on intesti-
outcome. Selected reviews and animal and in vitro studies nal function and adaptation in short bowel syndrome
were used as supporting literature. (SBS)34,35; one observational study of the effects of bovine
colostrum supplementation in patients with type II
Quality assessment diabetes36; seven trials concerning the prevention
and/or treatment of upper respiratory tract infection
The methodological quality of the included studies was (URTI) or gastroenteritis37–42; four trials concerning the
evaluated using the three-item Jadad scale,23 which has modulation of innate or adaptive immunological
been used extensively in clinical research and has shown a responses43–46; one single-blind, uncontrolled RT evaluat-
high degree of inter-rater reliability.24,25 It is used to evalu- ing the effect of bovine colostrum in infants and children
ate three domains of study quality: randomization, blind- with nonorganic failure to thrive47; two RTs evaluating the
ing, and withdrawals/dropouts. Scores range from 0 to 5, effects of bovine colostrum on irritable bowel syndrome48
with higher scores indicating better quality (≥3 = method- and juvenile idiopathic arthritis49; a case series evaluating
ologically sound). Studies that did not employ a compara- the effect of bovine colostrum in chronic pain syn-
tive methodology, such as those evaluating the effect of an drome50; and 24 trials investigating athletic performance,
intervention without a control group or crossover design, body composition, nutrient absorption, and endocrino-
were given a default score of 0. The 2011 impact factor (in logical or immune functions during exercise in healthy
Journal Citation Reports) of the journal in which each subjects.51–74
study was published was recorded, if available.
Methodological quality
RESULTS
Jadad scale scores ranged from 0 to 5 (mean, 2.8). Sixteen
Literature search trials (31%) were of poor methodological quality
(score ≤2). Only two trials obtained maximum scores.
The initial literature search identified 1,366 publications The median journal impact factor for the included studies
(Embase, n = 427; CINAHL, n = 32; Global Health, was 2.48 (range, 0.521–5.43). Impact factor was not asso-
n = 359; Cochrane Library, n = 60; Medline, n = 488). Four ciated with the assigned methodological ratings.
additional papers were identified through other sources.
After the removal of duplicates (n = 581), 789 papers Ineligible studies
remained eligible for screening. Screening identified 49
papers that reported on 51 studies of the effect of bovine The literature search identified several studies that were
colostrum supplementation that met the eligibility crite- not eligible for inclusion in this review, including two
ria. Figure 1 is a flowchart of the study selection process. trials that used lactoferrin from bovine colostrum75,76; one
study investigating the use of a colostrum-containing
Trial characteristics mouth hygiene product in Sjögren’s syndrome and oral
lichen planus77; one study investigating the effect of
The 51 studies included in the analysis were conducted in colostrum-containing eye drops for the treatment of eye
Europe (n = 24, 47%), the United States (n = 8, 16%), Asia dryness78; one study investigating the effect of topical

Figure 1 Flowchart of the study selection process.
Abbreviations: BC, bovine colostrum; HBC, hyperimmune bovine colostrum.
colostrum on dental plaque79; and two studies of inflam- in vitro, animal, and human studies have suggested that
matory bowel disease, comprising one double-blind, bovine colostrum supplementation protects against the
placebo-controlled RT of colostrum enemas80 and one adverse effects of these drugs in the gut.26,82–85 Playford
small case study investigating the use of a dietary supple- et al.82 found that bovine colostrum supplementation
ment containing a range of different substances that resulted in a dose-dependent reduction in gastric injury
included, among others, bovine colostrum. In this last after indomethacin administration in a rat model and
study, however, it would be impossible to attribute an prevented villus shortening in a mouse model of
effect to bovine colostrum.81 indomethacin-induced small intestinal injury. Other
authors found that bovine colostrum alone or in combi-
nation with glutamine reduced NSAID-induced declines
DISCUSSION AND SUMMARY OF STUDIES in serum total protein and albumin levels as well
as the NSAID-induced increase in intestinal permeabil-
NSAID- and surgery-induced gut damage ity, resulting in reduced bacterial overgrowth and
less bacterial translocation to the mesenteric lymph
NSAIDs are widely prescribed due to their analgesic, anti- nodes, liver, spleen, and peripheral blood.83,86 Bovine
inflammatory, and antipyretic effects. Their use, however, colostrum has also effectively reduced bacterial translo-
may have severe adverse effects, such as gastric ulceration cation in rats with carrageenan-induced intraperitoneal
and injury to the small and large intestines. The results of inflammation.87

Table 1 Overview of the studies included in the review.
Reference Population No. of subjects (M/F) Study design Exposure or condition Dosage and duration Endpoints Jadad score Outcomes
NSAID- and surgery-induced
gut damage
Playford et al. (2001)26 Healthy volunteers 7 (7/0) R; DB; PC; CRO Indometacin 50 mg t.i.d. 125 mL t.i.d. for 7 days Intestinal permeability 4 ↓Intestinal permeability
Playford et al. (2001)26 NSAID users 15 (7/8); 14 finished R; DB; PC; CRO NSAID use for ≥1 year 125 mL t.i.d. for 7 days Intestinal permeability 4 No significant effect
Bolke et al. (2002)32 Coronary bypass patients 60 (54/6) R; PC; level of Coronary bypass 42 g 2 days preoperatively Endotoxin; ENC; CRP; IL-6 3 No significant effect
blinding NS
Nutrition Reviews® Vol. 72(4):237–254

Bolke et al. (2002)33 Abdominal surgery 40 (22/18) R; PC; level of Abdominal surgery 56 g 3 days preoperatively Endotoxin; ENC; CRP; IL-6 2 ↓Endotoxin; ↑ENC
patients blinding NS
HIV-associated diarrhea and
immunosuppression
Saxon & Weinstein 2 AIDS patients, 1 other 3 (3/0) Case series Cryptosporidium 1, 3, or 5 L for 5–7 days Diarrhea 0 No significant effect
(1987)27
28
Rump et al. (1992) 27 adult HIV patients, 2 37 (31/6) OBS; UC Diarrhea (>4 stools/day) 10 g daily for 10 days Stool frequency; body weight 0 ↓Stool frequency; body weight
pediatric HIV patients, 8 for >2 weeks stable
others
Plettenberg et al. (1993)29 HIV-positive adults 25 (25/0) OBS; UC Diarrhea (≥3 stools/day) 10 g daily for 10 days Stool frequency 0 ↓Stool frequency
for ≥1 month
30
Flóren et al. (2006) HIV-positive adults 30 (15/15) OBS; UC Diarrhea (≥4 stools/day) 16 g b.i.d. for 4 weeks Stool frequency; self-reported fatigue; 0 ↓Stool frequency;↓ fatigue;↑CD4+
for ≥5 days CD4+ count; body weight count; ↑body weight
31
Kaducu et al. (2011) HIV-positive adults not 87 (27/60) R; open Diarrhea (≥4 stools/day) 16 g b.i.d. for 4 weeks Stool frequency; self-reported fatigue; 3 ↓Stool frequency;↓fatigue; ↑CD4+
receiving ARV for ≥7 days CD4+ count; body weight count;↑body weight
Sports nutrition and
exercise
Antonio et al. (2001)51 Recreational athletes 22 (14/8); 21 finished DB; PC Maintain habitual level of 20 g daily for 8 weeks 1-RM; maximum repetitions; TTE; LBM 2 ↑LBM
exercise
54
Coombes et al. (2002) Competitive cyclists 42 (42/0); 28 finished R; DB; PC Habitual level of exercise 20 or 60 g daily for 8 VO2max test; time trial; IGF-1; body 3 ↑Time trial results
weeks composition
56
Buckley et al. (2002) Recreational athletes 30 (30/0) R; DB; PC Three 45-min runs/week 60 g for 8 weeks Peak running speed in 2 consecutive 3 ↑Peak running speed in 2nd run
runs; IGF-1
Hofman et al. (2002)74 Elite field hockey players 35 (18/17); 28 finished R; DB; PC Habitual level of exercise 60 g for 8 weeks Sprint test; suicide test; shuttle run; 3 ↑Sprint test performance
vertical jump; anthropometrics
59
Brinkworth et al. (2002) Elite rowers 13 (0/13) R; DB; PC Rowing and strength- 60 g for 9 weeks Mechanical work in 2 consecutive rows; 4 ↑Blood buffering capacity
plyometric training body composition; blood buffering
73
Kuipers et al. (2002) Endurance athletes 9 (9/0) OBS; UC Tested before and after 60 g for 4 weeks IGF-1; IGF-BP3; urine drug test 0 No significant effect
Fry et al. (2003)62 Recreational athletes 19 (13/6) R; DB; PC Heavy-resistance exercise 60 g for 12 weeks (4 1-RM; fiber type percentage; fiber type 3 No significant effect
4 days/week groups) area; myosin heavy chain; body
composition
Buckley et al. (2003)57 Recreational athletes 51 (51/0) R; DB; PC Resistance training 3×/ 60 g daily for 8 weeks Vertical jump;, cycling power; alactic 4 ↑Vertical jump; ↑cycling power
week, nonresistance work capacity; 1-RM; IGF-1
exercises
Brinkworth & Buckley Healthy males 12 (12/0) R; DB; PC OGTT; OATT 60 g for 8 weeks OGTT; OATT 4 No significant effect
(2003)60
a
Brinkworth & Buckley Elite rowers 13 (0/13) R; DB; PC Rowing and 60 g for 9 weeks Plasma buffering capacity 4 No significant effect
(2004)61 strength-plyometric
training
241
242
Table 1 Continued
Reference Population No. of subjects (M/F) Study design Exposure or condition Dosage and duration Endpoints Jadad score Outcomes
Brinkworth et al. (2004)58 Recreational athletes 34 (34/0) R; DB; PC 4 days/week, resistance 60 g for 8 weeks Limb circumference; limb CSA; 4 ↑Limb circumference; ↑limb CSA
training of elbow maximum voluntary isometric
flexors in nondominant strength; 1-RM
arm
Mero et al. (2005)63 Recreational athletes 12 (12/0) R; DB; PC; CRO Heavy strength training 20 g for 2 weeks IGF-1; strength performance; S-amino 4 ↑S-essential amino acids; ↑protein
session acids; protein balance; muscle biopsy synthesis and breakdown
53
Shing et al. (2006) Highly trained cyclists 29 (29/0) R; DB; PC Habitual level of exercise 10 g for 8 weeks and 40-km time trial; VO2max test; TTE 3 Improved 40-km time trial after
and 5 days of HIT 1 day HIT; ↑ventilatory threshold
66
Kerksick et al. (2007) Recreational athletes 49 (36/13) R; DB; PC Total-body resistance 60 g for 12 weeks FFM; 1-RM and 80% of 1-RM; 30-sec 4 ↑FFM
training (4 groups) sprint tests
Immune functions in
sport and exercise
Mero et al. (1997)64 Recreational athletes 9 (9/0) R; DB; PC; CRO 8 days strength and 125 or 25 mL for 8 days IGF-1; IgA; IgG; countermovement 3 ↑IGF-1 for 125 mL
speed training; 13 days jump; hormones; amino acids
washout
Mero et al. (2002)65 Recreational athletes 30 (16/14) R; DB; PC Habitual level of exercise 20 g for 2 weeks IGF-1; IgA; IgG 4 ↑IGF-1; ↑secretory IgA
Crooks et al. (2006)69 Recreational distance 39 (22/17); 35 R; DB; PC Habitual level of exercise 26 g (10 g colostrum) for Salivary IgA; self-reported URTS 4 ↑Salivary IgA
runners analyzed 12 weeks
Shing et al. (2007)52 Elite cyclists 29 (29/0) R; DB; PC Habitual level of exercise 10 g for 8 weeks and NK cell toxicity; salivary IgA; cytokines; 4 ↑IgG2; ↑sTNF-1; ↑cytotoxic T cells
and 5 days of HIT 1 day IgG; CRP; lymphocyte and neutrophil
surface markers; URTS
Buckley et al. (2009)55 Recreational athletes 30 (30/0) R; DB; PC Running at lactate 60 g for 8 weeks Intestinal permeability; body mass; 3 ↑Intestinal permeability
threshold 3 days/week peak oxygen uptake; TTE; heart rate
Davison & Diment Recreational athletes 20 (20/0) R; DB; PC 2 h of exercise at 64% 20 g for 28 days In vitro neutrophil degranulation; 3 ↑Speed of neutrophil
(2010)68 VO2max salivary IgA; lysozyme; blood lactate; degranulation; ↑lysozyme
blood glucose; P-cortisol concentration and secretion
Crooks et al. (2010)70 Elite swimmers, 25 (12/13); 28 (9/10) R; DB; PC 12 weeks swim training 50 g for 10 weeks Saliva and blood IgA; IgM; IgG; URTS 4 No significant effect
nonexercising controls corresponding to 20 g
of colostrum
Marchbank et al. (2011)67 Recreational athletes 12 (12/0) DB; PC; CRO 20-min run at 80% VO2max 20 g for 14 days Gut hormones; intestinal permeability 2 ↓Intestinal permeability; ↓GLP-1
Carol et al. (2011)71 Well-trained athletes 10 (10/0); 9 analyzed R; DB; PC; CRO Glycogen depletion trial; 25 g for 10 days Plasma glucose; lactate; serum cortisol; 4 No significant effect
endurance trial cell counts; Ig; CRP and cytokines
Appukutty et al. (2011)72 Adolescent athletes 40 (40/0) R; DB; PC Habitual level of exercise 20 g daily for 6 weeks In vitro IFN-γ 4 ↓In vitro IFN-γ
Infection and immune
responses
McClead et al. (1988)37 Males >16 years with 45 (45/0) R; PC BC, HBC, or water 2 g twice Stool volume; stool IgG and IgA; 1 No effect on stool volume; ↑stool
V. cholera diarrhea toxin-neutralizing activity IgG; ↑stool IgA
37
McClead et al. (1988) Males >16 years with 20 (20/0) R; PC BC, HBC, or water 2g×8 Stool volume; stool IgG and IgA; 1 No effect on stool volume; ↑stool
V. cholera diarrhea toxin-neutralizing activity IgG; ↑stool IgA
42
Huppertz et al. (1999) Children with 27 (13/14) R; DB; PC Infection with 21 g for 14 days Stool frequency; elimination of strains 4 ↓Stool frequency
diarrheagenic E. coli diarrheagenic E. coli expressing virulence factors
44
He et al. (2001) Healthy adult volunteers 18 (9/9) R; PC; level of Oral vaccine against 100 mL for 7 days Antibody-secreting cells; CR6 IgG 2 No significant effect
blinding NS S. typhi Ty21a receptors
Brinkworth & Buckley Healthy volunteers 174 (174/0) R; DB; PCb Participants in earlier 60 g for 8 weeks Self-reported URTS 4 ↓Self-reported URTS
(2003)38 trials
Patel & Rana (2006)39 Patients aged 1–8 years 605 (341/210); 551 Open; UC Recurrent URTI or 3 g for 12 weeks Self-reported URTS; diarrhea; 0 ↓Self-reported URTS; ↓diarrhea;
finished diarrhea hospitalization ↓hospitalization

Lindbaek et al. (2006)40 Male soldiers NS R; DB; PC Nonstreptococcal sore NS Illness duration 2 No significant effect
throat
Wolvers et al. (2006)45 Healthy adult volunteers 138 (42/89); 131 R; DB; PC Tetanus toxoid vaccine; 1.2 g daily DTH; leukocyte subsets; phagocytosis; 3 No significant effect
finished typhoid vaccine oxidative burst; lymphocyte
proliferation

Patiroglu & Kondolot Children with IgA 31 (18/13) R; DB; PC Clinically established 14 mg t.i.d. for 1 week Self-reported severity score; URTS 5 ↓Self-reported severity score
(2013)41 deficiency URTI duration; salivary IgA
Mikic et al. (2012)43 Healthy adult volunteers 20 (6/14) R; no placebo 480 mg b.i.d. for 30 days Salivary IgA 3 ↓Salivary IgA
Jensen et al. (2012)46 Healthy adult volunteers 12 (6/6) R; DB; PC; CRO 150 mg once Phagocytic activity; leukocyte counts 4 ↑Phagocytic activity; ↓NK cells
and subsets; T and NK cell counts
Short bowel syndrome
Lund et al. (2012)34 Adult patients with SBS 12 (7/5); 8 analyzed R; DB; PC; CRO SBS in clinically stable 500 mL daily Grip strength; lung function; body 3 No significant effect
phase composition; intestinal function
Aunsholt et al. (2014)35 Children with SBS 9 (5/4) R; DB; PC; CRO SBS in clinically stable 20% enteral intake for 4 Intestinal energy absorption; wet 5 No significant effect
phase weeks weight; growth; IGF-1; IGF-BP3
Growth and metabolic
disorders
Kim et al. (2009)36 Adults with type 2 18 (9/9) OBS; UC Type 2 diabetes 10 g daily Postprandial blood glucose; 0 ↓Postprandial blood glucose;
diabetes triglycerides; cholesterol; ketone ↓triglycerides; ↓cholesterol;
bodies ↓ketone bodies
Panahi et al. (2010)47 Children with failure to 120 (71/49) R; SB; UC Nonorganic failure to 40 mg/kg/day Gomez and Waterlow indices 2 ↑Gomez index of growth
thrive thrive insufficiency
Juvenile idiopathic arthritis
Malin et al. (1997)49 Children with JIA 30 (13/17) R; C; DB JCA 10 g TNF-α; ISC; sACS fecal enzymes; TNF-α 4 ↑Fecal urease
and α-1-antitrypsin
Chronic pain syndrome and
irritable bowel syndrome
Ragab et al. (2007)48 Adults with IBS 110 (85/25)c R; PC; DB Adults with IBS 10 mL daily for 2 weeks, IBS symptoms 4 No effect at end of treatment
followed by 20 mL
daily for 10 weeks
Waaga-Gasser et al. Adults with CPS 4 (2/2) Case series CPS with good response 20 g–1 g daily Flow cytometry; cytokine analysis; 0 Apoptotic effect on monocytes
(2009)50 to BC therapy IGF-1; apoptosis
Abbreviations and symbols: ↓, decrease; ↑, increase; 1-RM, one-repetition maximum; ARV, anti-retroviral therapy; BC, bovine colostrum; C, controlled; CPS, chronic pain syndrome; CR, complement receptor; CRO, crossover; CRP, C-reactive protein;
CSA, cross-sectional area; DB, double-blind; DTH, delayed-type hypersensitivity; ENC, endotoxin-neutralizing capacity; F, female; FFM, fat-free mass; GLP-1, glucagon-like peptide 1; HBC, hyper-immune bovine colostrum; HIT, high-intensity
training; IBS, irritable bowel syndrome; IFN-γ, interferon gamma; Ig, immunoglobulin; IGF-1, insulin-like growth factor 1; IGF-BP3, insulin-like growth factor binding protein 3; IGF-1, insulin-like growth factor 1; IL-6, interleukin-6; ISC,
immunoglobulin-secreting cells; JIA, juvenile idiopathic arthritis; JCA, juvenile chronic arthritis; LBM, lean body mass; M, male; NK, natural killer; NS, not stated; NSAID, non-steroidal anti-inflammatory drug; OATT, oral L-alanine tolerance test;
OBS, observational; OGTT, oral D-glucose tolerance test; PC, placebo-controlled; R, randomized; sACS, specific antibody-secreting cells; SB, single-blind; SBS, short bowel syndrome; sTNF-1, soluble tumor necrosis factor 1; TNF-α, tumor necrosis
factor α; TTE, time to exhaustion; UC, uncontrolled; URTI, upper respiratory tract infection; URTS, upper respiratory tract symptoms; VO2max, maximal oxygen uptake.
a
Data collected in previous study.59
b
Pooled retrospective data from earlier trials.
c
Contradiction between text and table.
243
Although the mechanisms of such beneficial effects study33 included 40 patients undergoing intra-abdominal
of bovine colostrum remain undetermined, the presence surgery who received the immunoglobulin-enriched
of growth factors is thought to contribute to the mainte- colostrum preparation (56 g) or placebo for 3 days
nance of equilibrium of mucosal mass and integrity in the preoperatively. Endpoints included serial evaluation of
GI tract.11 This proposal is supported by in vitro evidence endotoxin levels during the first 7 days postsurgery. Com-
that bovine colostrum increases proliferation and migra- pared with patients receiving placebo, those receiving the
tion of human colonic carcinoma cells and rat intestinal colostrum preparation had significantly lower endotoxin
cells, suggesting that it has the ability to stimulate growth levels, indicating that the loss of endotoxin-neutralizing
and repair in the GI tract.82 Furthermore, the C-terminal capacity was reduced.33 In a similar study,32 60 patients
half of the colostrum protein lactoferrin has the ability to undergoing coronary bypass surgery were randomized to
sequester unbound NSAIDs in the GI tract and may receive the colostrum preparation (42 g for 2 days) or
thus protect against NSAID-induced gastropathy.85 A placebo. Colostrum supplementation did not reduce the

mouse model of C-lobe and NSAID coadministration amount of endotoxin in the bloodstream or shorten
showed significant reduction of gastric bleeding and the duration of postoperative endotoxemia.32 Notable dif-
inflammation.84 ferences in the designs of these studies, other than the
Despite the promising results in animal models, few type of surgery, were the colostrum dose and the duration
human trials on this topic have been undertaken. Playford of supplementation. Neither study found any effect of
et al.26 conducted two crossover RTs evaluating the effects colostrum supplementation on the clinical course of
of bovine colostrum on NSAID-induced intestinal patients.
damage. In the first study, 7 healthy male volunteers Available evidence suggests that bovine colostrum
received colostrum (125 mL, 3 times per day for 7 days) supplementation may reduce microbial translocation
or an isoproteinaceous milk whey protein solution. Fol- across the gut mucosa in patients undergoing abdominal
lowing microfiltration (0.2 μm pore), the colostrum surgery. Such an effect may be attributable to direct anti-
(Bioenervi; Viable Bioproducts, Turku, Finland) was free microbial and endotoxin-neutralizing effects as well as to
of fat and lactose and reduced in major proteins such as the suppression of gut inflammation and the promotion
casein and lactalbumin, with the remaining protein being of mucosal integrity and tissue repair.
relatively rich in immunoglobulin and growth factors.
Subjects also received indomethacin (50 mg, 3 times per HIV-associated diarrhea and immunosuppression
day) for the last 5 days. Intestinal permeability was
assessed at baseline and after 7 days. Bovine colostrum Diarrhea is a common complication of HIV infection,
supplementation significantly reduced the NSAID- with a multifactorial etiology that may include common
induced increase in intestinal permeability. In the second pathogens, opportunistic agents, or noninfectious factors.
study, 15 patients who had taken nonselective NSAIDs HIV infection may lead to the loss of gut-mucosal CD4+
for at least 1 year received 125 mL of the same colostrum cells, thereby compromising the epithelial barrier func-
preparation or a milk whey protein solution 3 times per tion of the gut mucosa and enabling microbial transloca-
day for 7 days, with a 2-week washout period between tion, resulting in GI and systemic immune activation.
study arms. Bovine colostrum supplementation had no Thus, HIV-associated diarrhea may not only result in
significant direct effect on gut permeability, but baseline discomfort and malnutrition but may also affect the
gut permeability in patients taking NSAIDs was similar to immunological and inflammatory status of patients.16,89
or lower than that in control subjects not receiving This review includes five studies of the role of bovine
NSAIDs.26 These studies provided evidence that bovine colostrum in HIV-associated diarrhea.27–31 Although the
colostrum or a derivative thereof may protect the GI tract studies are generally of poor methodological quality
from NSAID-induced injury. However, further clinical (Table 1), they collectively suggest a positive effect of
studies of sufficient power evaluating outcomes in bovine colostrum supplementation. In an open, uncon-
patients who have taken NSAIDs for longer periods of trolled, observational study, Rump et al.28 administered
time are warranted. 10 g of bovine colostrum concentrated for immuno-
Two placebo-controlled RTs investigating the effects globulin to 27 adults and 2 children with HIV infection.
of bovine colostrum supplementation on inflammatory The colostrum product was a casein-precipitated, fat-
responses and microbial translocation after surgery were free, spray-dried powder.88 This treatment led to trans-
included in this review.32,33 Both studies used Lactobin ient or long-lasting normalization of stool frequency
(Biotest Pharma, Dreieich, Germany), a spray-dried in the majority of patients. Plettenberg et al.29 per-
immunoglobulin-enriched powder.88 The placebo formed an open, uncontrolled study in 25 HIV-infected
product was an identical mix of formula and raspberry patients with chronic diarrhea with no demonstrable
flavor without the colostrum preparation. The first pathogen (n = 18) or cryptosporidiosis (n = 7). Ten days

of supplementation with 10 g of bovine colostrum used the same standardized,low-heat,low-fat,low-lactose,
(Lactobin)88 led to complete remission in 40% (10/25) of concentrated bovine colostrum powder (Intact; Numico
patients. Research Australia Pty Ltd, Adelaide, Australia) and a
In an open-label observational study, Florén et al.30 whey-protein-based control supplement.53,54,56–62,73,74 Mero
investigated the effect of a porridge containing 32% et al.63 used a freeze-dried colostrum product (Dynamic
bovine colostrum powder (ColoPlus; ColoPlus AB, colostrum; Hi-Col, Oulu, Finland) and a maltodextrin
Malmö, Sweden). Consumption of this preparation placebo, while Antonio et al.51 used powdered whole
reduced HIV-associated diarrhea, with a significant colostrum (Symbiotics, Sedona, AZ, USA) and a whey
decrease in the daily number of bowel evacuations. protein concentrate placebo. Kerksick et al.66 used a colos-
Fatigue decreased by 81% during the study period. Fur- trum powder not further specified and an isocaloric and
thermore, patients showed concomitant increases in isonitrogenous blend of whey and casein placebo in addi-
hemoglobin and albumin concentrations, CD4+ counts, tion to creatine.

and body weight. These findings were confirmed in a In a placebo-controlled RT conducted in 29 male
2011 open-label RT involving 87 adult patients with HIV elite cyclists, Shing et al.53 found that supplementation
who were not receiving antiretroviral therapy. The with 10 g of colostrum daily improved cycling perfor-
patients were randomized to colostrum supplementation mance after 5 days of high-intensity training while reduc-
for 28 days (porridge containing 32% bovine colostrum ing the decrease in the ventilatory threshold. Similarly, a
powder, ColoPlus) or standard care. Patients receiving double-blind placebo-controlled trial in 35 elite field
supplementation showed a significant reduction in diar- hockey players randomized to receive 60 g of bovine
rhea, with a decrease in daily stool frequency from 7.3 to colostrum daily or whey protein concentrate for 8 weeks
1.3, and an 85% decrease in self-reported fatigue, which showed that colostrum improved sprint performance and
was significantly greater than that reported by controls. significantly reduced sprint times compared with the
CD4+ counts increased by 14% and body weight increased whey protein group.74 Buckley et al.57 found that supple-
by 11% in colostrum-treated patients.31 Because these mentation with 60 g of bovine colostrum daily had sig-
studies used porridges containing 32% bovine colostrum nificant beneficial effects on peak cycling and vertical
and no placebo, improved nutritional status may have jumping powers after 8 weeks, but not after 4 weeks,
contributed significantly to the observed effects.30,31 suggesting that the duration of supplementation may be
Current evidence, however, suggests that bovine colos- important.
trum can effectively ameliorate HIV-associated diarrhea, The findings of animal studies have suggested that
possibly due to direct antimicrobial and endotoxin- the effect of bovine colostrum on athletic performance is
neutralizing effects and the suppression of gut inflamma- related to better recovery after exercise.90 In humans,
tion as well as to the promotion of mucosal integrity and Buckley et al.56 tested peak speed in two consecutive runs
tissue repair. These findings must be confirmed in future separated by a 20-min recovery period. Colostrum
placebo-controlled RTs. supplementation (60 g daily) for 8 weeks did not improve
performance in the first run but significantly increased
Sports nutrition and exercise peak speeds in the second run. These findings were sup-
ported in a study of 28 male competitive cyclists.54 Eight
The effect of bovine colostrum supplementation on ath- weeks of bovine colostrum supplementation (20 g or
letic performance has received considerable attention, 60 g) significantly improved the amount of work com-
primarily based on the hypothesis that bovine colostrum pleted in a second bout of exercise after 2 hours of cycling
may improve nutrient absorption and body composition. at 65% maximal oxygen uptake compared with placebo,
The high levels of growth factors known to stimulate but no significant difference between doses was detected.
protein synthesis, in addition to early findings that bovine These results suggest an improved ability to recover after
colostrum supplementation increased IGF-1 concentra- exercise, independent of colostrum dosage.54
tions in male sprinters,64 have prompted interest in Some studies have found that colostrum affects body
the possible effects of bovine colostrum on body composition,51,58,66 whereas others have not.54,59,62,74 The
composition, muscle strength, and endurance in active IGF-1 in bovine colostrum is structurally identical to that
individuals. in humans,91 and an increase in the serum IGF-1 level
This review includes studies conducted with induced by bovine colostrum supplementation may have
competitive-level53,54,59,74 and recreational51,57,58,62,63,66 ath- positive effects on protein synthesis and body composi-
letes. Several studies found that bovine colostrum had tion. Some authors have found that bovine colostrum
positive effects on various aspects of athletic perfor- supplementation increases serum IGF-1 levels,64,65
mance,53,54,56,57,74 whereas others were not able to confirm whereas others have been unable to confirm these find-
these findings.51,58,59,61–64,66,73 The majority of the studies ings.35,54,56,57,73 Similarly, the effect on nutrient absorption

capacity demonstrated by some authors63 has not been received particular attention, although numerous other
confirmed by others.60,64 No impact of bovine colostrum immune variables have been investigated.
supplementation has been found on plasma cortisol, In a double-blind RT, Shing et al.52 found that, com-
growth hormone, or testosterone level.64,68,71 pared with a whey-protein-based control supplement,
In a randomized controlled trial,66 49 healthy sub- 10 g of colostrum (Intact) per day prevented postexercise
jects received supplements of 60 g of colostrum, casein/ reduction in IgG2 levels and cytotoxic/suppressor
whey, creatine, or combinations thereof. The two CD3+CD8+ T cells in 29 male cyclists. These effects were
combinations of whey/casein protein plus creatine and demonstrated after a period of prolonged stress-inducing
colostrum plus creatine both led to greater increases in exercise. In contrast, Carol et al.71 compared 25 g of
fat-free mass. This result, however, may have been due to skimmed freeze-dried colostrum and a skimmed milk
the addition of creatine. Thus, no conclusion regarding placebo and found no effect of colostrum on measured
the effect of colostrum can be drawn from this study.66 A immune variables after short-term intense exercise in 10

double-blind, placebo-controlled trial in 22 recreational healthy male athletes.
athletes supplemented with 20 g of colostrum for 8 weeks Secretory IgA is known to serve as the first line of
documented significantly increased lean body mass as defense in protecting mucosal surfaces from enteric
measured by dual-energy X-ray absorptiometry, leading toxins and pathogenic microorganisms, thereby playing a
the authors to suggest that colostrum supplementation key role in the protection of the respiratory, GI, and geni-
had an anabolic effect.51 This proposal was supported by tourinary tracts.93
the findings that supplementation with 60 g daily for 8 In a study of 20 healthy subjects, Davison and
weeks during resistance training increased limb circum- Diment68 found increased stimulated neutrophil
ference and cross-sectional area compared with placebo58 degranulation speed in vitro 1 hour after exercise and
and that 2 weeks of supplementation with 20 g of colos- reduced exercise-induced alterations in lysozyme con-
trum increased serum levels of essential amino acids.63 In centration and secretion in subjects who received a
a study of 12 healthy adult males, however, 8 weeks of bovine colostrum powder supplement (Neovite, London,
colostrum supplementation had no effect on intestinal UK) versus an isocaloric isomacronutrient mix of milk
nutrient absorption.60 Thus, while evidence supports con- protein concentrate and skimmed milk powder. In agree-
tinuous research on the effects of bovine colostrum on ment with the findings of other studies, these authors
sports performance, body composition, and nutrient found no effect on IgA concentration.64,70 Other authors,
absorption, these data are not unequivocal. Studies in this however, have documented significantly increased sali-
area have generally been of acceptable methodological vary IgA levels after bovine colostrum supplementa-
quality but are often limited by a small number of par- tion.65,69 Mero et al.65 reported a 33% increase in salivary
ticipants. Moreover, studies have used heterogeneous IgA levels in healthy athletes after 2 weeks of daily supple-
endpoints, producing contradictory results, many of mentation with 20 g of freeze-dried colostrum (Dynamic
which remain unconfirmed. colostrum) versus a maltodextrin placebo. This finding
was supported by the study of Crooks et al.,69 who found
Immune function in sport and exercise that 12 weeks of bovine colostrum supplementation
(Immunolac; NZMP Ltd, Auckland, New Zealand) sig-
Strenuous exercise may cause immunosuppression that nificantly increased salivary IgA levels compared with a
affects the innate and adaptive immune systems, increas- skimmed milk placebo in 39 long-distance runners. In a
ing athletes’ susceptibility to infection, particularly URTI. subsequent study of 25 elite swimmers and 28 students
While prolonged intense exercise may increase the risk of randomly assigned to receive bovine colostrum or
infection, moderate exercise, on the other hand, may placebo, however, Crooks et al.70 found that a low-protein
improve the ability to resist URTI, illustrating the com- colostrum powder had no effect on salivary immuno-
plexities of these mechanisms.92 Although the relation- globulin levels compared with an isocaloric placebo of
ship between exercise and URTI is poorly understood skimmed milk powder and milk protein concentrate.
and may depend on several individual determinants, the Another aspect of comprised immunity in athletes is
identification of several immune-activating and antimi- the exercise-induced increase in gut permeability. In a
crobial factors in colostrum has led to the hypothesis that placebo-controlled crossover RT in 12 healthy male sub-
colostrum intake may support or stimulate immune jects, bovine colostrum powder reduced the exercise-
functions in athletes.19 induced increase in intestinal permeability compared
Several studies have investigated the potential of with an isoenergetic isomacronutrient mix of milk
bovine colostrum supplementation to prevent postexer- protein concentrate and skimmed milk powder. In vitro
cise immune suppression.38,52,55,64,65,67–72 Mucosal defenses investigations suggested that this effect was due to
and levels of secretory immunoglobulin (Ig) A (IgA) have reduced temperature-induced apoptosis in HT29 cells

and enhanced induction of heat-shock protein.67 Of of URTI or diarrhea during the previous 6 months. Colos-
further interest, bovine colostrum was shown to signifi- trum was supplied as a powder (Pedimune; Merck Ltd,
cantly reduce heat-induced gut hyperpermeability in a rat Mumbai, India). The number of URTI episodes was
model. In rats whose core body temperature was raised, reduced by 73.0%, 83.3%, and 91.2% at 4, 8, and 12 weeks,
significantly less 51Cr-EDTA transferred into the blood- respectively, compared with the number of episodes in
stream of colostrum-fed rats compared with rats fed a the first 6 months prior to enrollment. The number of
control diet.94 Another study in 30 healthy male subjects55 diarrhea episodes and the frequency of hospitalization for
found increased intestinal permeability in those who con- URTI or diarrhea were also significantly reduced.39 Other
sumed 60 g of bovine colostrum daily (Intact) compared authors, however, have pointed out the numerous limita-
with those who received a whey-protein-based control tions and poor methodological quality of this study.95
supplement. There was, however, no increase in intestinal First, it used an open, uncontrolled design that relied only
permeability due to the exercise protocol; thus, these on self-reported symptoms. Second, the authors appear

results are inconclusive with respect to the effects of exer- to have compared the rates of URTI and diarrhea at 4,
cise on gut permeability. 8, and 12 weeks with baseline values collected over 6
Exercise-induced immune depression is of months without converting them to monthly rates, which
multifactorial origin. Prolonged intense training may unsurprisingly yielded results indicating significantly
have measurable effects on leukocyte counts, oxidative fewer episodes. Thus, the results of this study require
burst activity, natural killer cell activity, mucosal immu- cautious interpretation.
noglobulin levels, and proinflammatory cytokine release, Patiroglu and Kondolot41 investigated the adminis-
but no correlation between these surrogate markers and tration of an oral lozenge (Igazym; ASSOS Ltd, Vejle,
immunocompetence has been established and thus the Denmark) containing 14 mg of colostrum and 2.2 mg of
effect of a change in one or more parameters with regard lysozyme or a placebo lozenge 3 times per day for 1 week
to in vivo immune capability is unclear. Overall, exercise in 31 children aged 5–16 years with known IgA deficiency
studies have not provided conclusive evidence for the and clinical signs of URTI. The presence of viral infection
effects of colostrum on immunity, but observations of was determined clinically, and etiologies were not con-
humoral immunity are of potential interest and deserve firmed by laboratory investigation. No difference in seri-
further investigation and confirmation. ally tested salivary IgA levels was observed between
groups, but 1 week of colostrum supplementation
Infection and immune responses reduced infection severity scores compared with placebo.
Similarly, 43.8% of patients in the colostrum group and
This review included nine articles reporting on 7 13.3% in the placebo group reported cessation of
adult37,38,40,52,69,70 and 3 pediatric39,41,42 studies of the treat- symptoms, but this difference was not significant.41
ment and prevention of URTI and diarrhea. In a double- Finally, McClead et al.37 observed no difference in stool
blind, placebo-controlled RT, Brinkworth and Buckley38 frequency in adult males infected with Vibrio cholerae
retrospectively pooled data from several previous studies who received defatted, casein-precipitated bovine colos-
examining self-reported URTI symptoms in 174 healthy trum, hyperimmune bovine colostrum, or water, while
adult males receiving bovine colostrum (Intact) or a Huppertz et al.42 demonstrated a significant reduction in
whey-protein-based control supplement. Significantly stool frequency in an RT of 30 children with diarrhea
fewer subjects receiving bovine colostrum reported URTI caused by E. coli expressing Shiga toxin (Stx) 1, Stx2, both
symptoms within 7 weeks after discontinuation of the Stx1 and Stx2, intimin, or enterohemorrhagic E. coli
intervention compared with those receiving placebo. (EHEC) hemolysin. The colostrum preparation used,
Bovine colostrum had no effect on symptoms once they Lactobin,88 was compared with placebo. The composition
had developed.38 Shing et al.52 reported a trend toward a of the placebo was not specified in the paper.
reduced incidence of upper respiratory illness in a study These data suggest that bovine colostrum has a
of 29 male cyclists. Crooks et al.69,70 observed similar prophylactic effect against URTI, which may correspond
trends. Lindbaek et al.40 performed a randomized to the findings of increased salivary IgA levels in
placebo-controlled study comparing the effects of bovine athletes receiving colostrum supplementation. These
colostrum and placebo on illness duration in patients data, however, are primarily self-reported and were
with nonstreptococcal sore throat, but results were pre- obtained by pooling study results that were not individu-
sented for a single cohort and few details of the trial were ally significant. The studies are heterogeneous with
provided. regard to population, colostrum dosage and formulation,
Patel and Rana39 conducted an open-label, methodological quality, and results. Thus, this effect of
noncomparative study of 3 g of daily bovine colostrum bovine colostrum must be confirmed in further well-
supplementation in 551 children after recurrent episodes designed, prospective, placebo-controlled studies.

Two studies investigating the effect of bovine colos- growth factors, growth hormones, and luminal nutri-
trum on the immune response to immunization in ents.96 The high amounts of intestinotrophic factors in
healthy subjects were identified.44,45 He et al.44 conducted colostrum have generated research interest in the hope
a randomized study in 18 healthy subjects receiving that colostrum supplementation might improve intesti-
100 mL of sterile filtered bovine colostrum (Bioenervi) nal adaptation and absorption in patients with SBS.
per day for 7 days or water colored with riboflavin food In an animal study of 4-week-old piglets that under-
color. On days 1, 3, and 5, the volunteers received oral went small bowel resection, colostrum feeding increased
vaccines against Salmonella typhi Ty21a. No significant villus height and crypt depth.97 In similar studies using a
difference in IgA, IgG, IgM, Fcγ, or complement receptor preclinical piglet model of SBS, investigators found that
expression on neutrophils and monocytes was observed colostrum supplementation increased circulating levels of
between groups. The authors noted a trend toward a glucagon-like peptide 2, IGF-1, and IGF binding protein 2
greater increase in specific IgA among subjects receiving and resulted in weight gain and muscle hypertrophy,

bovine colostrum. leading them to suggest the possibility of enhanced post-
In a double-blind, placebo-controlled RT,45 138 operative intestinal adaptation in colostrum-fed pigs.98,99
healthy volunteers receiving 1.2 g of bovine colo- Nevertheless, while some studies have suggested that
strum, a mixture of micronutrients, bovine colos- colostrum improves intestinal adaptation after small
trum plus micronutrients, or placebo were given tetanus bowel resection, others have not been able to confirm this
toxoid and typhoid vaccines after 6 weeks of supplemen- finding.100
tation. Supplementation with bovine colostrum had Two studies, one in adults34 and one in children,35
no effect on the immune parameters assessed. The examining the possible beneficial effect of bovine colos-
bovine colostrum concentrate (Proventra; GalaGen Inc., trum in SBS were identified. In both studies, the investi-
Minnetonka, MN, USA) was a spray-dried, sterile filtered gators used whole colostrum sterilized by electron beam
powder from the whey fraction of nonspecific bovine irradiation. The placebo was prepared as a nutrient-
colostrum, and the placebo was an isocaloric powdered matched mix of semi-skimmed milk, cream, and whey
drink based on skim milk powder, sugar, and protein powder. Lund et al.34 investigated the effects of
maltodextrin. In another randomized study,43 supple- 250 mL of colostrum and control supplementation twice
mentation with 480 mg of colostrum 2 times per day per day on intestinal function and adaptation in adult
significantly reduced secretory IgA levels in 20 healthy patients with SBS using a randomized, double-blind,
volunteers. These contradictory results may be attribut- crossover design. The treatments were separated by a
able to the use of test subjects with good health and nutri- 4-week washout period. Complete datasets were obtained
tional status and without exercise-induced immune from 8 of 12 patients, and colostrum was not superior to
perturbation. In a recent single-dose crossover RT, Jensen the control supplement.34 In another placebo-controlled
et al.46 tested the effect of a low-molecular-weight crossover RT in 9 clinically stable children with SBS,35
immunoglobulin-depleted fraction of bovine colostrum 20% of the daily enteral fluid intake was replaced with
or a rice flour placebo in 12 healthy subjects, finding bovine colostrum and a milk-mix control diet, separated
increased phagocytic activity of monocytes and by a 4-week washout period. Colostrum did not improve
polymorphonuclear cells, an increased white blood cell energy or wet-weight absorption in metabolic balance
count, and a transient decrease in the circulation of studies, growth evaluated by knemometry (a noninvasive
natural killer cells, while Appukutty et al.72 found modu- technique of lower leg length measurement used for the
lated in vitro interferon-γ activity after 6 weeks of colos- study of short-term growth), or levels of IGF-1 or IGF
trum supplementation in adolescent athletes. These binding protein 3. After colostrum supplementation, all
results suggest that bovine colostrum may, after contact subjects reported firmer feces and less frequent daily def-
with the gut mucosa, trigger immunological events that ecation. However, the mean weight of feces did not differ
are followed by systemic effects. between the two diets.35
Although few human studies have examined the
Short bowel syndrome effects of colostrum on SBS, and the results are thus
inconclusive, no evidence of a marked effect on intestinal
SBS is characterized by malabsorption and consequent function has been documented in this patient group. Evi-
malnutrition in patients devoid of parts of the small dence from animal studies showing the beneficial prop-
intestine as the result of massive surgical resection or erties of colostrum in SBS is based on studies in newly
congenital defects. Intestinal adaptation after small bowel operated animals, suggesting that intestinal adaptation
resection is believed to be pivotal in the ability of patients leading to functional and structural changes is more plau-
to sufficiently absorb fluid, electrolytes, and nutrients and sible.98 The capacity of bovine colostrum to facilitate such
may be influenced by several factors, including peptide changes in the human intestine has yet to be determined.

The absence of a beneficial effect in clinically stable colostrum-treated patients,49 but the implication of this
patients with SBS is in line with the notion that bovine finding is not clear.
colostrum supplementation may be most beneficial
during inflammation and/or mucosal damage17 and cor-
Irritable bowel and chronic pain syndromes
responds to the findings of earlier studies demonstrating
that bovine colostrum does not affect intestinal nutrient
One RT evaluating the effect of bovine colostrum
absorption in healthy adults.60
(Immuno-Dynamics) on irritable bowel syndrome was
identified. The study was placebo controlled, but the
Disorders of growth and metabolism nature of the placebo was not stated. The study included
110 adult patients and showed no significant effect
In a recent study conducted in mice with streptozotocin- of colostrum supplementation at the end of the study
induced diabetes, an IGF-rich bovine colostrum fraction period.48

significantly reduced blood glucose and improved organ One case series evaluated the effect of bovine colos-
weights, suggesting that this fraction may be valuable in trum (Lactobin88) on chronic pain syndrome.50 The
the treatment of patients with diabetes.101 This review authors suggested that colostrum induced apoptosis
identified one study examining metabolic control in regulation in monocytes in these patients, but this con-
patients with diabetes.36 Sixteen patients with type 2 dia- clusion relied on in vitro evidence from four patients and
betes ingested 5 g of pasteurized, powdered bovine colos- should be interpreted cautiously.
trum (Immuno-Dynamics, Inc., Fennimore, WI, USA)
twice daily for 4 weeks and were followed longitudinally;
Dosage and formulation of supplementation
the same patients served as pre- and postinterventional
controls. The authors found a continuous decrease in
The optimal dosage and duration of bovine colostrum
postprandial blood glucose levels throughout the study
supplementation have not been established. Most studies
period. Total cholesterol, triglyceride, and ketone body
have been conducted in healthy adults using doses that
levels also decreased significantly. Although these find-
range from 14 mg 3 times per day to 60 g daily. Few
ings suggest that bovine colostrum has a positive effect on
studies have directly compared different dosage regi-
metabolic control in type 2 diabetes, the mechanisms and
mens.54,64 Furthermore, standardization of bioactivity,
actual benefit remain unestablished.
which is influenced by breed, herd, milking times, and
The possible anabolic effect and the potential ability
formulation, is complicated and has not been attempted
of colostrum to improve nutrient absorption have led to
consistently.12,13 Thus, simple expressions of dosage in
speculation about the usefulness of colostrum supple-
weight units are not sufficiently informative with regard
mentation in managing failure to thrive. In a single-blind
to the bioactivity of the constituents of colostrum.
clinical RT in 120 children diagnosed with nonorganic
Several commercial colostrum products are avail-
failure to thrive, subjects received 40 mg/kg/day bovine
able,5 a number of which were used in the studies reviewed
colostrum for 3 months or standard care. Colostrum was
here, including Lactobin (Biotest Pharma), a spray-dried
supplied as capsules containing pasteurized lyophilized
immunoglobulin-enriched powder88; Intact (Numico
bovine colostrum. Supplementation significantly
Research Pty Ltd), a low-heat, low-fat, low-lactose concen-
improved the Gomez, but not the Waterlow, index of
trated bovine colostrum powder; Pedimune colostrum
growth insufficiency.47 The study is inconclusive with
powder (Merck); ColoPlus (ColoPlus AB), a porridge con-
regard to the possible role of bovine colostrum supple-
taining 32% bovine colostrum; Dynamic colostrum (Hi-
mentation in nonorganic failure to thrive because the
Col), a freeze-dried colostrum powder; a powdered whole
results are contradictory and the study has obvious weak-
colostrum (Symbiotics); Bioenervi (Viable Products), a
nesses, such as the single-blind design and the lack of a
sterile, filtered, colostrum-based product; a pasteurized,
placebo group.
powdered bovine colostrum (Immuno-Dynamics); IgG
Plus (Smart-Naco, Kuala Lumpur, Malaysia); and Igazym
Juvenile idiopathic arthritis (ASSOS Ltd), a lozenge containing bovine colostrum and
lysozyme.
One randomized, placebo-controlled study evaluating the Some studies used a complete colostrum product,
effect of sterile, filtered, freeze-dried bovine colostrum whereas others used fractions or concentrated formula-
versus a human Lactobacillus strain GG or hyperimmune tions, with concentrations consisting primarily of protein
bovine colostrum on juvenile chronic arthritis showed no and IgG. Most authors have reported the protein and/or
clinical effect or paraclinical outcomes relevant for IgG content of formulations, rendering this the only com-
disease control. It did show increased urease activity in parable operational parameter among studies. However,

different dairy processes, such as heat treatment, tissue repair.26,28–31,33,38,41 Among the numerous future
ultrafiltration, freeze-drying, and the removal of lipid, applications of bovine colostrum, some have been high-
casein, lactose, and salts, affect the bioactive components lighted as warranting additional attention.11
of bovine colostrum. An overview of the effect of differ- Necrotizing enterocolitis (NEC) is a common and
ent processing steps can be found in the work of devastating disease in the preterm neonate that compro-
Elfstrand et al.13 The use of concentrated formulations mises GI integrity and function. Nutrition is considered
may preclude the inclusion of other possibly bioactive important in the prevention and management of NEC.103
and immunologically active substances. Thus, formula- In the present review, no eligible study examining the use
tion and sterilization methods should be considered and of bovine colostrum in patients with NEC or neonatal
reported. septicemia was identified. However, such treatment may
Bioactive compounds of interest may vary with the become an area of interest,11 as animal studies using
focus of research.Although the effect of bovine colostrum bovine colostrum and human trials using bovine

may depend on the concentration of a specific constitu- lactoferrin have been conducted.1,5,75,76,104–106 Most con-
ent for a particular condition, possible benefits may also vincingly, the beneficial effects of bovine colostrum have
rely on the combined effects of various factors. Thus, the been demonstrated repeatedly in a well-established piglet
effective dose may depend on the condition or outcome model of preterm infants. Colostrum was superior to
as well as the subjects or population studied. Table 2 com- infant formula as the initial diet because it improved both
pares the colostrum dosage and the protein and IgG con- gut maturation and resistance against bacterial infection
tents in studies included in this review. It may serve as a and NEC.1,104,106,107 Thus, bovine colostrum or derivatives
guide for determining such contents and dosage in future thereof should be considered when developing novel
studies. therapeutic strategies for the prevention of NEC and
Furthermore, when reading or planning studies that sepsis in preterm infants. When planning studies using
evaluate the effects of bovine colostrum, considerations bovine colostrum in infants, there may be concern that
about the optimal choice of control supplement may be exposure to cow milk protein before the age of 6 months
important. In the majority of the studies included in this increases the risk of cow milk allergy, particularly in pre-
review, the investigators used either whey protein powder disposed infants. All protocols should ask for parental
or a mix of milk powder and protein powder. It seems heredity, as the majority of the allergic babies have one or
important that, with regard to macronutrient composi- two parents who have atopic disease, and infants positive
tion, control supplements either be similar or isocaloric for this variable should not be given the product.108 The
and matched. use of colostrum at this age should preferably be
restricted to infants with specific symptoms or circum-
Safety and adverse effects stances, such as prematurity.
Furthermore, when considering nutritional interven-
There were no reports of serious side effects or toxicities tions in full-term and premature infants, the aspect of
in the 51 studies, which included a total of 2,326 partici- growth is important because the optimal feeding strategy
pants. Reported side effects were mild and included com- may influence not only growth but also neurocognitive
plaints of an unpleasant taste, nausea, flatulence, diarrhea, outcomes.109 Colostrum contains a mixture of proteins,
skin rash, and unspecified abdominal discom- such as immunoglobulin, and a range of growth factors.
fort.28,29,34,39,66,69 Nine studies specifically reported an This mixture does not necessarily promote rapid growth,
absence of side effects.26,30,33,41,42,47,55,74 In general, bovine but its potential to accelerate growth needs further study.
colostrum is considered safe and well tolerated.21,102 Bovine colostrum has been proposed to play a role in
the treatment or prevention of chemotherapy-induced
mucositis,and evidence suggests possible beneficial effects
FUTURE PERSPECTIVES on the oral mucosa.11 Intestinotrophic factors in bovine
colostrum may promote epithelial integrity and tissue
Many questions about the effects and mechanisms of repair, and antimicrobial proteins and peptides may
action of bovine colostrum remain unanswered. Cur- have direct antimicrobial and endotoxin-neutralizing
rently available data suggest that most benefits of bovine capabilities and reduce gut inflammation and microbial
colostrum derive from its immune-modulating capabili- translocation. Administration of cheese whey extract
ties, which are utilized in the maintenance or improve- to methotrexate-treated rats improved intestinal mor-
ment of host defenses under different detrimental phology and function in the treated animals. Similar
conditions or immune system exposures, or its ability results were seen in colostrum-fed, busulfan-treated, and
to aid in the maintenance of GI mucosal integrity by cyclophosphamide-treated piglets.110,111 A study designed
suppressing gut inflammation and promoting mucosal to investigate the effect of bovine colostrum on GI

Table 2 Overview of colostrum dosage and corresponding protein and IgG content in studies of enterally
ingested bovine colostrum.
Reference Ratio of protein/IgG Dosage Protein content IgG content Effect (Y/N)
NSAID- and surgery-induced gut damage
Playford et al. (2001)26 4.3 g/L/– 375 mL 1.6 g – Y
Playford et al. (2001)26 4.3 g/L/– 375 mL 1.6 g – N
Bolke et al. (2002)32 80/65a 42 g 33.6 g 27.3 g N
Bolke et al. (2002)33 80/65a 56 g 44.8 g 36.4 g Y
HIV-associated diarrhea and immunosuppression
27
Saxon and Weinstein (1987) –/– 1–5 L – – N
Rump et al. (1992)28 –/60 10 g – 6g Y
Plettenberg et al. (1993)29 –/45 10 g – 4.5 g Y
Flóren et al. (2006)30 23b/7.4 32 g 23 g 7.4 g Y
31 b
Kaducu et al. (2011) 23 /7.4 32 g 23 g 7.4 g Y
Sports nutrition and exercise
Antonio et al. (2001)51 79/– 20 g 15.8 g – Y

Coombes et al. (2002)54 75/15c 20 g or 60 g 15/45 g 3/9 g Y
56 c
Buckley et al. (2002) 75/15 60 g 45 g 9g Y
Hofman et al. (2002)74 75/15c 60 g 45 g 9g Y
Brinkworth et al. (2002)59 75/15c 60 g 45 g 9g Y
Kuipers et al. (2002)73 75/15c 60 g 45 g 9g N
62 c
Fry et al. (2003) 75/15 60 g 45 g 9g N
Buckley et al. (2003)57 75/15c 60 g 45 g 9g Y
Brinkworth & Buckley (2003)60 75/15c 60 g 45 g 9g N
Brinkworth & Buckley (2004)61 75/15c 60 g 45 g 9g N
58 c
Brinkworth et al. (2004) 75/15 60 g 45 g 9g Y
Mero et al. (2005)63 30/22.5 20 g 6g 4.5 g Y
Shing et al. (2006)53 75/15c 10 g 7.5 g 1.5 g Y
Kerksick et al. (2007)66 –/– 60 g – – Y
Immune functions in sport and exercise
Mero et al. (1997)64 –/0.39 g/L 125/25 mL – 0.05 g/0.01 g Y
Mero et al. (2002)65 30/22.5 20 g 6g 4.5 g Y
Crooks et al. (2006)69 33/–d 10 g 8.6 g – Y
Shing et al. (2007)52 –/20 10 g – 2g Y
Buckley et al. (2009)55 75/15c 60 g 45 g 9g Y
Davison & Diment (2010)68 52/– 20 g 10.4 g – Y
Crooks et al. (2010)70 31.6/2.9d 20 g 6.32 g 0.58 g N
67
Marchbank et al. (2011) 80/15–20 20 g 16 g 3–4 g Y
71
Carol et al. (2011) –/– 25 g – – N
Appukutty et al. (2011)72 –/– 20 g – – Y
Infection and immune responses
McClead et al. (1988)37 –/– 4g – – N
McClead et al. (1988)37 –/– 16 g – – N
Huppertz et al. (1999)42 80/65a 21 g 16.8 g 13.7 g Y
He et al. (2001)44 –/– – – – N
Brinkworth & Buckley (2003)38 75/15c 60 g 45 g 9g Y
Patel & Rana (2006)39 –/– 3g – – Y
Lindbaek et al. (2006)40 –/– – – – N
Wolvers et al. (2006)45 –/– 1.2 g – ≈0.5 g N
Patiroglu & Kondolot (2013)41 –/–e 0.042 g – – Y
43
Mikic et al. (2012) –/– 0.96 g – – Y
Jensen et al. (2012)46 –/– – – – Y
Short bowel syndrome
Lund et al. (2012)34 106/50 g/Lf 500 mL 53 g 25 g N
Aunsholt et al. (2012)35 110/35 g/Lg 20% of intake – – N
Growth and metabolic disorders
Kim et al. (2009)36 56.6/26 10 g 5.66 g 2.6 g Y
Panahi et al. (2010)47 –/– 40 mg/kg – – Y
Juvenile idiopathic arthritis
Malin et al. (1997)49 –/39 10 g 3.9 g Y
Chronic pain syndrome and irritable bowel syndrome
Ragab et al. (2007)48 –/– – – – N
Waaga-Gasser et al. (2009)50 –/– 1–20 g – – Y
Abbreviations and symbols: –, Not stated; N, no; NSAID, nonsteroidal anti-inflammatory drug; Y, yes.
a
Total immunoglobulin content, not only IgG.
b
Protein content of full product containing 32% bovine colostrum.
c
Not stated in all manuscripts, but referenced here.18
d
Also contains protein from other sources.
e
Also contains lysozyme.
f
IgG content stated to >50 mg/mL.
g
IgG content stated to >3.5%. In some manuscripts, it may not be clear whether the IgG content is expressed as an absolute value or as a percentage of
the total protein content.

toxicity in children receiving chemotherapy is currently Acknowledgments
under way (www.clinicaltrials.gov, identification number:
NCT01766804). Funding. This work was funded in part by a research
Studies of primary Sjögren’s syndrome and oral grant from the Danish Child Cancer Foundation and by
lichen planus have provided support for the role of Odense University Hospital research funds.
topically applied bovine colostrum in oral mucosa
maintenance.77 Such topical application, although not Declaration of interest. The authors have no relevant
considered in this review, may be a novel approach to interests to declare.
alleviate oral manifestations of these diseases. The use of
bovine colostrum in the treatment of inflammatory bowel Authors’ contributions. MR and SH conceived the idea
disease has received little attention, and this review iden- and designed the study. MR performed the literature
tified no such eligible trial, but colostrum enemas ame- search, carried out quality assessment, and drafted and
finalized the manuscript. SH, PTS, and KM critically

liorated symptoms of distal colitis in one trial.80 These
data support the role of topical bovine colostrum appli- reviewed the manuscript. All authors approved the final
cation in inflammatory bowel disease and point to the version submitted for publication.
need for further randomized controlled studies of suffi-
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Clinical applications of bovine colostrum therapy:

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