The Immune and Gastrointestinal Benefits of Colostrum

From Top-Notch Athletes to the Critically Ill, this Colostral “First Milk” Provides Nutritional Protection

What’s the nutritional superfood almost all of us have had at some time in our life, and new mothers, dairy farmers, and Ob/Gyn’s know best? It’s colostrum, the first milk that comes at birth. Colostrum is particularly important for a newborn infant because they lack a fully developed immune system. Colostrum provides important immunological factors such as immunoglobulins, lactoferrin, oligosaccharides, and cytokines, as well as many growth factors to support the developing infant’s digestive tract and beyond.[1],[2] These factors also interact with the intestinal microbiome, and promote the population of healthy bacteria.[3]

Perhaps needless to say, when colostrum is consumed as a supplement, it is not derived from a human host, but rather is a product of the dairy industry. Differences exist between human and bovine colostrum (BC), with BC having high levels of immunoglobulin G (IgG), while in human colostrum levels of immunoglobulin A (IgA) are the highest.[4],[5] High levels of IgG in BC are important because the offspring of hooved mammals do not develop passive immunity prenatally, it must be provided after birth.[6] Because of its critical importance for the development of the calf, the process of collection for our use of its healing components occurs after the necessary amount has been fed to the calf to provide this passive immunization. [7]

Numerous studies have shown that consumption of BC may increase our immunity to infection in a similar manner. Interesting research has considered the use of colostrum immunoglobulins from cows that have been vaccinated against common diseases such as rotavirus to protect humans from infection as well as a treatment for infection.[8],[9],[10] Hyperimmune BC has also been successfully used in this manner for the treatment and/or prevention for human disease caused by Cryptosporidium sp.,Shigella sp., enterotoxigenic Escherichia coli, and Clostridium difficile infection.[11] The protection hyperimmune BC may provide is not limited to enteric infections – data strongly suggests it also may protect against highly virulent forms of the influenza virus in a similar fashion.[12]

BC is not just protective against infection, the many factors found in it also may help protect against allergies and asthma. Perhaps this is not surprising as many may be familiar with the epidemiological studies showing a lower incidence of allergic disease in breast fed infants.[13],[14],[15] Of the many active components, transforming growth factor (TGF)-β, found in both human and bovine colostrum,[16],[17] plays an important role in regulating inflammation and the development of oral tolerance.[18] In mice, administration of BC has been shown to promote a Th1 response, reducing levels of the cytokine interleukin (IL)-4 which is associated with Th2 (allergic) immune response.[19]

Finally, colostrum plays an important role in the maturation of the gut and other tissues. One factor in colostrum which may play an important role in this is epidermal growth factor (EGF).[20] EGF promotes normal development of the gut, lungs, and skin, protecting infants from necrotizing enterocolitis, chronic lung disease, and respiratory distress syndrome.[21],[22],[23] Insulin-like growth factor (IGF) is found at high levels in BC and also plays a role in tissue development and growth.[24] Studies suggest IGF also may be a factor that helps protect the intestinal barrier and promote repair.[25],[26]

Herein, we take a deeper look at the clinical data backing the use of BC for the treatment and prevention of infection, for the support of healthy gut integrity, and data in these settings specific to athletes as well.

Influenza

In addition to the many studies investigating the use of hyperimmune BC as treatment and a preventative for common gastrointestinal infections, BC also has been investigated in high risk cardiovascular disease patients as an alternative or adjunctive to influenza vaccination.[27] One of the challenges with influenza vaccination, of course, is viral mutation or the emergence of new viral strains. As the typical influenza vaccine is based on projections from common viral strains the previous year, these selections may be inaccurate. A good example is the seasonal flu vaccine in 2018 – 2019 which was reported by the Centers for Disease Control (CDC) to only be 29% effective.[28] BC has been proposed as an alternative because it provides a broad spectrum of immunoglobulins against common pathogens.[29]

In this two-stage study,[27] the first stage included healthy individuals divided into four arms: group A received only the flu vaccine, group B received the flu vaccine + 400 mg of freeze dried BC daily, group C received only 400 mg of BC/day, and group D had no prophylaxis. The period of oral supplementation was 8 weeks and vaccinations were within two weeks of the initiation of the study. Assessment at three months showed no significant differences between the groups B and C (both receiving BC), however, group A (receiving only the vaccine) had approximately four times more episodes of the flu and three times the number of days with illness symptoms. These parameters in the vaccine group were only slightly better than the group receiving no prophylaxis. The number of days with malaise was highest in the vaccine group, even considerably higher than the control group, suggesting the vaccine itself also had this adverse effect.

In the second stage of the study,[27]high-risk cardiovascular disease patients were divided into three treatment arms using the same protocol as the first stage, however, in this portion of the study all groups received some form of treatment and there was no group D. Of the three treatments, both groups receiving BC had only three events of cardiopulmonary problems while the group only having vaccination had six events resulting in one death. The incidence of hospital admissions was also significantly higher in the group only having vaccination.

Common Pediatric Infections

Perhaps not surprisingly, BC has been considered as a therapy in many pediatric settings. Often available as a powder that can easily be mixed into other dairy products or a smoothie, this also contributes to its common use in children. In one such study of a population of children (age range one to six years) with recurrent diarrhea or upper respiratory tract infections (URTIs), daily supplementation of 3 or 6 g (depending on age) of BC for four weeks was shown to significantly reduce number of URTIs, episodes of diarrhea, and hospital admissions.[30] Additionally, even though the period of intervention was only for four weeks, the reduction in infectious events was maintained at two and six months.

A randomized, double-blind, placebo-controlled trial (RDBPCT) also evaluated the effectiveness of BC for the treatment of acute viral or bacterial diarrhea in children ranging in age from six months to two years.[31] Children were given 3 g of BC or placebo in addition to standard of care with oral rehydration solution and supplemental zinc per the World Health Organization guidelines. At 48 hours, it was found that the children additionally receiving BC had a significantly lower frequency of vomiting, diarrhea, and Vesikari scores (a composite diarrheal disease severity score[32]) compared to those receiving the placebo.

A 2019 meta-analysis of randomized controlled trials further supports the use of BC for the reduction of childhood infectious diarrhea concluding “In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection.”[33]

Adult Respiratory Tract Infection

Supplementation with BC also has been shown to reduce the incidence of URTI symptoms in adults as well. In a RDBPCT of healthy active males, daily supplementation of 60 g of BC daily for eight weeks significantly reduced the proportion of subjects reporting URTI symptoms compared to placebo.[34] In elite swimmers, daily supplementation of 25 g of BC also reduced reported URTI symptoms by week four of the intervention, with even lower reporting of symptoms the remainder of the 10 week intervention.[35]

Intestinal Permeability

As mentioned, multiple growth factors found in colostrum also impact the health of the gut lining. In addition to animal models showing protection against the adverse gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) and chemotherapy,[36],[37] human studies have also demonstrated BC has positive effects in these settings.

In healthy volunteers, coadministration of BC with indomethacin prevented the medication-induced increase in intestinal permeability, which increased three-fold after five days in the control group taking a placebo along with the medication.[38] In children with newly diagnosed acute lymphocytic leukemia, daily supplementation with BC alongside chemotherapy significantly reduced the severity of oral mucositis compared to those receiving placebo.[39] Finally, in a study of critically ill patients hospitalized in the intensive care unit (diagnosis unspecified), after 10 days of supplementation of BC improvements were seen in intestinal permeability (assessed by plasma zonulin level), plasma endotoxin level, and the incidence of diarrhea.[40]

There are not yet human studies in the setting of inflammatory bowel disease (IBD), a condition in which we also see increased gut permeability along with inflammation that typifies the disease. However, given the positive findings from numerous animal models of IBD[41] and high level of tolerability of BC in populations including the severely ill, we should anticipate studies in this population soon as well.

Exercise-Associated Immune and Gut Dysfunction

Although regular moderate exercise is proven to have numerous health benefits, exercise that is extremely high intensity, of prolonged duration, or under other extreme conditions can have adverse effects including increased risk of infection and increased intestinal permeability.[42],[43],[44],[45],[46] Because BC has data suggesting it may ameliorate both of these issues and contains growth factors like IGF that may further enhance training, it has been investigated in numerous studies with athletes.

Clinical studies have shown routine supplementation of BC during training attenuates aspects of exercise-associated immune dysfunction by increasing secretory IgA levels,[47] total lymphocyte counts and CD4+:CD8+ ratio,[48] salivary lysozyme level, and neutrophil function.[49] Additional positive effects on training were seen with a reduction in exercise-induced muscle damage and markers of inflammation.[50]

In regard to gastrointestinal tract dysfunction, supplementation with BC has been shown to decrease intestinal injury incurred during hot-climate exercise[51] and attenuate the exercise-related increase in intestinal permeability by 80%.[52] In athletes already amidst peak training activities, lactulose and mannitol absorption tests showed that 75% had increased intestinal permeability, which was restored to normal range and significantly lower than baseline after 20 days of BC supplementation.[53]

Clearly, colostrum is a nutritional tool with substantial evidence showing its positive impact on human health, which likely can be traced back to the origins of humankind. Its broad range of benefits for all ages, and high level of tolerability even in the critically ill, make it a broadly useful tool to combat infection and gastrointestinal dysfunction in nearly all populations.

Dr. Carrie Decker graduated with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Prior to becoming a naturopathic physician, Dr. Decker was an engineer, and obtained graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectively. Dr. Decker continues to enjoy academic research and writing and uses these skills to support integrative medicine education as a writer and contributor to various resources. Dr. Decker supports Allergy Research Group as a member of their education and product development team.

References:


[1] Castellote C, et al. Premature delivery influences the immunological composition of colostrum and transitional and mature human milk. J Nutr. 2011 Jun;141(6):1181-7.

[2] Araújo ED, et al. Evaluation of the secretory immunoglobulin A levels in the colostrum and milk of mothers of term and pre-term newborns. Braz J Infect Dis. 2005 Oct;9(5):357-62.

[3] Aakko J, et al. Human milk oligosaccharide categories define the microbiota composition in human colostrum. Benef Microbes. 2017 Aug 24;8(4):563-567.

[4] Larson BL, et al. Immunoglobulin production and transport by the mammary gland. J Dairy Sci. 1980 Apr 1;63(4):665-71.

[5] Mathur NB, et al. Anti-infective factors in preterm human colostrum. Acta Paediatr Scand. 1990 Nov;79(11):1039-44.

[6] Langer P. Differences in the composition of colostrum and milk in eutherians reflect differences in immunoglobulin transfer. J Mammalogy. 2009 Apr 14;90(2):332-9.

[7] Borad SG, Singh AK. Colostrum immunoglobulins: Processing, preservation and application aspects. Int Dairy Journal. 2018 Oct 1;85:201-10.

[8] Ebina T, et al. Passive immunizations of suckling mice and infants with bovine colostrum containing antibodies to human rotavirus. J Med Virol. 1992 Oct;38(2):117-23.

[9] Davidson GP, et al. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet. 1989 Sep 23;2(8665):709-12.

[10] Sarker SA, et al. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatr Infect Dis J. 1998 Dec;17(12):1149-54.

[11] Steele J, et al. Hyperimmune bovine colostrum for treatment of GI infections: a review and update on Clostridium difficile. Hum Vaccin Immunother. 2013 Jul;9(7):1565-8.

[12] Ng WC, et al. Prevention and treatment of influenza with hyperimmune bovine colostrum antibody. PLoS One. 2010 Oct 26;5(10):e13622.

[13] Morales E, et al. Effects of prolonged breastfeeding and colostrum fatty acids on allergic manifestations and infections in infancy. Clin Exp Allergy. 2012 Jun;42(6):918-28.

[14] Oddy WH. Breastfeeding, Childhood Asthma, and Allergic Disease. Ann Nutr Metab. 2017;70 Suppl 2:26-36.

[15] Silvers KM, et al. Breastfeeding protects against current asthma up to 6 years of age. J Pediatr. 2012 Jun;160(6):991-6.e1.

[16] Elfstrand L, et al. Immunoglobulins, growth factors and growth hormone in bovine colostrum and the effects of processing. Int Dairy J. 2002 Jan 1;12(11):879-87.

[17] Savilahti E, et al. IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and development of atopy by age 4. Pediatr Res. 2005 Dec;58(6):1300-5.

[18] Rautava S, Walker WA. Academy of Breastfeeding Medicine founder’s lecture 2008: breastfeeding–an extrauterine link between mother and child. Breastfeed Med. 2009 Mar;4(1):3-10.

[19] Yoshioka Y, et al. Oral administration of bovine colostrum stimulates intestinal intraepithelial lymphocytes to polarize Th1-type in mice. Int Immunopharmacol. 2005 Mar;5(3):581-90.

[20] Ganz S, et al. [Substances in the bovine colostrum – a survey]. Tierarztl Prax Ausg G Grosstiere Nutztiere. 2018 Jun;46(3):178-189.

[21] Shin CE, et al. Diminished epidermal growth factor levels in infants with necrotizing enterocolitis. J Pediatr Surg. 2000 Feb;35(2):173-6; discussion 177.

[22] Currie AE, et al. Epidermal growth factor in the lungs of infants developing chronic lung disease. Eur Respir J. 2001 Nov;18(5):796-800.

[23] Nanney LB, et al. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol. 1990 Jun;94(6):742-8.

[24] Pakkanen R, Aalto J. Growth factors and antimicrobial factors of bovine colostrum. Int Dairy J. 1997 May 1;7(5):285-97.

[25] Huang KF, et al. Insulin-like growth factor 1 (IGF-1) reduces gut atrophy and bacterial translocation after severe burn injury. Arch Surg. 1993 Jan;128(1):47-53.

[26] Chen K, et al. Insulin-like growth factor-I prevents gut atrophy and maintains intestinal integrity in septic rats. JPEN J Parenter Enteral Nutr. 1995 Mar-Apr;19(2):119-24.

[27] Cesarone MR, et al. Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino. Clin Appl Thromb Hemost. 2007 Apr;13(2):130-6.

[28] Centers for Disease Control and Prevention. Influenza (Flu): CDC Seasonal Flu Vaccine Effectiveness Studies. Available at https://www.cdc.gov/flu/vaccines-work/effectiveness-studies.htm. Accessed April 2, 2020.

[29] Stephan W, et al. Antibodies from colostrum in oral immunotherapy. J Clin Chem Clin Biochem. 1990 Jan;28(1):19-23.

[30] Saad K, et al. Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children. Medicine (Baltimore). 2016 Sep;95(37):e4560.

[31] Barakat SH, et al. Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial. J Trop Pediatr. 2020 Feb 1;66(1):46-55.

[32] Freedman SB, et al. Evaluation of a gastroenteritis severity score for use in outpatient settings. Pediatrics. 2010;125:e1278–85.

[33] Li J, et al. Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea. Sci Rep. 2019 Feb 28;9(1):3093.

[34] Brinkworth GD, Buckley JD. Concentrated bovine colostrum protein supplementation reduces the incidence of self-reported symptoms of upper respiratory tract infection in adult males. Eur J Nutr. 2003 Aug;42(4):228-32.

[35] Crooks C, et al. Effect of bovine colostrum supplementation on respiratory tract mucosal defenses in swimmers. Int J Sport Nutr Exerc Metab. 2010 Jun;20(3):224-35.

[36] Cairangzhuoma, et al. Skimmed, sterilized, and concentrated bovine late colostrum promotes both prevention and recovery from intestinal tissue damage in mice. J Dairy Sci. 2013 Mar;96(3):1347-55.

[37] Pontoppidan PE, et al. Bovine Colostrum Modulates Myeloablative Chemotherapy-Induced Gut Toxicity in Piglets. J Nutr. 2015 Jul;145(7):1472-80.

[38] Playford RJ, et al. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001 Jun;100(6):627-33.

[39] Rathe M, et al. Bovine Colostrum Against Chemotherapy-Induced Gastrointestinal Toxicity in Children With Acute Lymphoblastic Leukemia: A Randomized, Double-Blind, Placebo-Controlled Trial. JPEN J Parenter Enteral Nutr. 2020 Feb;44(2):337-347.

[40] Eslamian G, et al. Effects of early enteral bovine colostrum supplementation on intestinal permeability in critically ill patients: A randomized, double-blind, placebo-controlled study. Nutrition. 2019 Apr;60:106-111.

[41] Menchetti L, et al. Potential benefits of colostrum in gastrointestinal diseases. Front Biosci (Schol Ed). 2016 Jun 1;8:331-51.

[42] MacKinnon LT. Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes. Immunol Cell Biol. 2000 Oct;78(5):502-9.

[43] Xu G, et al. Identification of Urinary Biomarkers for Exercise-Induced Immunosuppression by iTRAQ Proteomics. Biomed Res Int. 2020 Jan 23;2020:3030793.

[44] Walsh NP. Recommendations to maintain immune health in athletes. Eur J Sport Sci. 2018 Jul;18(6):820-831.

[45] Hałasa M, et al. Assessing the Association of Elevated Zonulin Concentration in Stool with Increased Intestinal Permeability in Active Professional Athletes. Medicina (Kaunas). 2019 Oct 21;55(10).

[46] Zuhl M, et al. Exercise regulation of intestinal tight junction proteins. Br J Sports Med. 2014 Jun;48(12):980-6.

[47] Crooks CV, et al. The effect of bovine colostrum supplementation on salivary IgA in distance runners. Int J Sport Nutr Exerc Metab. 2006 Feb;16(1):47-64.

[48] Zhang H. Amelioration of decline in immune function in athletes after high-intensity training by bovine colostrum. Cur Topics Nutra Res. 2019 May 1;17(2):219-22.

[49] Davison G, Diment BC. Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and enhances the recovery of neutrophil function after prolonged exercise. Br J Nutr. 2010 May;103(10):1425-32.

[50] Kotsis Y, et al. A low-dose, 6-week bovine colostrum supplementation maintains performance and attenuates inflammatory indices following a Loughborough Intermittent Shuttle Test in soccer players. Eur J Nutr. 2018 Apr;57(3):1181-1195.

[51] March DS, et al. The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat. Eur J Nutr. 2019 Jun;58(4):1441-1451.

[52] Marchbank T, et al. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G477-84.

[53] Hałasa M, et al. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes. Nutrients. 2017 Apr 8;9(4). pii: E370.