Colostrum
Colostrum, or first milk, is the first form of milk produced by the mammary glands of humans and other mammals immediately following delivery of the newborn.[1] It may be called beestings when referring to the first milk of a cow or similar animal.[2] Most species will begin to generate colostrum just prior to giving birth. Colostrum has an especially high amount of bioactive compounds compared to mature milk to give the newborn the best possible start to life. Specifically, colostrum contains antibodies to protect the newborn against disease and infection, and immune and growth factors and other bioactives that help to activate a newborn's immune system, jumpstart gut function, and seed a healthy gut microbiome in the first few days of life. The bioactives found in colostrum are essential for a newborn's health, growth and vitality.[1] Colostrum strengthens a baby's immune system and is filled with white blood cells to protect it from infection.
At birth, the surroundings of the newborn mammal change from the relatively sterile environment in the mother's uterus, with a constant nutrient supply via the placenta, to the microbe-rich environment outside, with irregular oral intake of complex milk nutrients through the gastrointestinal tract.[3] This transition puts high demands on the gastrointestinal tract of the neonate, as the gut plays an important part in both the digestive system and the immune system.[4] Colostrum has evolved to care for highly sensitive mammalian neonates and contributes significantly to initial immunological defense as well as to the growth, development, and maturation of the neonate's gastrointestinal tract by providing key nutrients and bioactive factors. Bovine colostrum powder is rich in protein and low in sugar and fat.[5][6] Bovine colostrum can also be used for a range of conditions in humans, and can boost a neonate's immunity.[7]
Colostrum also has a mild laxative effect, encouraging the passing of a baby's first stool, which is called meconium.[8] This clears excess bilirubin, a waste-product of dead red blood cells which is produced in large quantities at birth due to blood volume reduction from the infant's body and which is responsible for jaundice.
Bioactive components in colostrum
Newborns have very immature and small digestive systems, and colostrum delivers its bioactives in a very concentrated low-volume form. Colostrum is known to contain immune cells (as lymphocytes)[9][10] and many antibodies such as IgA, IgG, and IgM. These are some of the components of the adaptive immune system. Other immune components of colostrum include the major components of the innate immune system, such as lactoferrin,[11] lysozyme,[12] lactoperoxidase,[13] complement,[14] and proline-rich polypeptides (PRP).[15] A number of cytokines (small messenger peptides that control the functioning of the immune system) are found in colostrum as well,[16] including interleukins,[16] tumor necrosis factor,[17] chemokines,[18] and others.
Colostrum also contains a number of growth factors, such as insulin-like growth factors I (IGF-1),[19] and II,[20] transforming growth factors alpha,[21] beta 1 and beta 2,[22][23] fibroblast growth factors,[24] epidermal growth factor,[25] granulocyte-macrophage-stimulating growth factor,[26] platelet-derived growth factor,[26] vascular endothelial growth factor,[27] and colony-stimulating factor-1.[28]
Human colostrum
Colustrum, which is produced for the first two to four days after childbirth, enhances immunity[29][30] and is believed to have anti-inflammatory properties.[31] It is suggested infants fed with human colostrum have lower incidence of gastrointestinal infections.[32]
Human consumption of bovine colostrum
While it has long been understood that the colostrum a mother produces is vital to a newborn's health in the first few days of life, research has shown that bovine (cow) colostrum and its components can continue to support important biological activities when given to more mature children and adults, so that the benefits of colostrum can extend well beyond the neonatal period of development.[33]
Bovine colostrum and human colostrum are highly similar in their makeup, both containing many of the same antibodies, immune and growth factors, and other nutrients.[34] Because they share so many of the same components, the way they work in the body is also highly similar. The benefit of bovine colostrum for human health has been studied in many areas including:
- Immune health: Colostrum is composed of bioactives that support immune health, including immunoglobulins, immune modulators, and oligosaccharides. These bioactives have been shown to work together to support not only the immune system but also respiratory health in adults and children.[35][36][37]
- Digestive health: Colostrum is composed of bioactives that support digestive health, including immunoglobulins, growth factors, and oligosaccharides. These bioactives work together to maintain and support intestinal integrity and improve nutrient absorption, while its naturally occurring prebiotics feed beneficial bacteria and support a balanced gut in adults and children[38][39][40][41][42][43][44][45]
- Early life nutrition: While colostrum and breast milk are a critical part of newborn nutrition, research has shown that colostrum has continued benefits in children over the age of one. As a component in early life nutrition, colostrum can help to support children's immune systems, soothe digestive upsets, and otherwise support children's digestive health.[37][42][41][46][44]
- Sports nutrition: Bovine colostrum contains several bioactives that help support sports nutrition, including immunoglobulins and growth factors. These bioactives combine to help maintain a healthy immune system during the stress during athletic training, while supporting cellular proliferation and restitution as well as protein synthesis and soft tissue repair.[47][48][49][50]
There is also research suggesting that a large proportion of colostrum is not fit for human consumption "due to tremendous bacterial loads". Salmonella was also detected in 15% of unpasteurised samples.[51] Pasteurisation reduces the bioactive proteins many of the benefits rely upon, however.[52]
Colostrum use in animal husbandry
Colostrum is crucial for newborn farm animals. They receive no passive transfer of immunity via the placenta before birth, so any antibodies that they need have to be ingested (unless supplied by injection or other artificial means). The ingested antibodies are absorbed from the intestine of the neonate.[53][54][55][56][57] The newborn animal must receive colostrum within 6 hours of being born for maximal absorption of colostral antibodies to occur. Recent studies indicate that colostrum should be fed to bovines within the first thirty minutes to maximize IgG absorption rates.[58]
The role of colostrum for newborn animals is to provide nutrition, and essential protection against infection while the immune and digestive systems are developing and maturing. Bovine colostrum provides macro- and micro-nutrients, as well as growth factors, cytokines, nucleosides, oligosaccharides, natural antimicrobials, antioxidants; and a range of immunoglobulins such as IgG, IgA, IgD, IgM and IgE. It is well established that minimal levels of IgG are essential to prevent failure of passive transfer. The iron-binding glycoproteins lactoferrin and transferrin in bovine colostrum assist in attacking pathogens by impacting their cell membrane and making them more susceptible to the immune systems attack by neutrophils. Cytokines present in bovine colostrum enhance B and T cell maturation and increase endogenous antibody production. They also play a major role in regulation of epithelial cell growth and development, proliferation, and restitution. Transfer factors enhance the activity of T cells. Other growth and immune factors such as IGF-1, IGF-2, FGF, EGF, TGF, PDGF, etc.
Bovine colostrum's components benefit the immune and digestive health of animals of all ages and species. Bovine colostrum's vast array of bioactive components collectively increase resistance to infection and disease caused by a wide range of pathogens including bacteria and viruses. The quality of the colostrum is essential in providing the essential benefits. Both contaminated early bovine colostrum at the farm level or late transition milk or milk are poor sources of the important colostral components necessary to maintain life and achieve and maintain healthy animal maturation and homoeostasis. Bovine colostrum also is beneficial in repairing or healing intestinal damage as well as increasing the absorption of nutrients from the GI tract. These properties and benefits are consistent among human and animal species.
The transition from fetal to neonatal and shift from maternal to environmental reliance requires an abrupt immunological change. In calves, for example, colostrum provides a significant benefit in neonatal intestine development. This includes villus area, circumference, height and height/crypt ratio. Colostrum is critically important to calves and foals in order to prevent failure of passive transfer and death. Calves, foals and piglets with low IgG levels have an increased risk of morbidity and mortality. Bovine colostrum can be used to reduce the duration and severity of infections so it can be a useful tool to include in the reduction of antibiotic use. Finally, another important and valuable benefit of colostrum is in the reduction in scours and increase in average daily weight gain all of which have a significant farmer and ultimately consumer benefit.
Colostrum use in companion animals
Much like in humans and production animals, companion animal survival in the newborn stage of life is largely dependent upon colostrum. Companion animal immune systems require several weeks to several months in order to fully develop. Maternal antibodies provide benefit for a relatively short period of time so a gap exists with immune sufficiency where an animal is at risk of infection. Like humans, companion animal immune response changes with age where early life and later in life have similarities. That is, an immune bias whereby the animal has less of an ability to fend off infections and greater prevalence of allergy at both ends of the age spectrum. Stress also affects a companion animal's immune system including changes in environment, diet, etc. Maintaining gut microbial balance is key to maintaining a healthy immune system as well as mucosal integrity, similar to humans. Bovine colostrum has been demonstrated to benefit companion animal immunity and digestive health.
Bovine colostrum plays a role in increasing Ig levels, increasing lymphocyte proliferation stimulating activity and increasing phagocytosis activity. These are supported by other components of colostrum which further enhance the activity of the immune response. The iron binding glycoproteins lactoferrin and transferrin in bovine colostrum assist in attacking pathogens by impacting their cell membrane and making them more susceptible to the immune systems attack by neutrophils. Cytokines present in bovine colostrum enhance B and T cell maturation and increase endogenous antibody production. They also play a major role in regulation of epithelial cell growth and development, proliferation, restitution. Transfer factors enhance the activity of T cells. Other growth and immune factors such as IGF-1, IGF-2, FGF, EGF, TGF, PDGF, etc. Colostrum contains glycomacropeptides which help to regulate appetite.
Bovine colostrum has been shown to enhance immune response in animal models including canine, feline and equine animals including maintaining a higher level of vaccine antibody response over time and for a longer period than the vaccine alone. Animals fed colostrum had a significantly higher local immune status resulting in higher IgA through GALT stimulation. Colostrum also plays a key role in reduction or prevention of diarrhea and reduction in respiratory illness.
Bovine colostrum history of study and potential future applications
Dairy cattle are naturally exposed to pathogens and produce immunoglobulins against them. These antibodies are present in the cow's bloodstream and in the colostrum. These immunoglobulins are specific to many human pathogens, including Escherichia coli, Cryptosporidium parvum, Shigella flexneri, Salmonella species, Staphylococcus species,[59] and rotavirus (which causes diarrhea in infants). Before the development of antibiotics, colostrum was the main source of immunoglobulins used to fight bacteria. In fact, when Albert Sabin made his first oral vaccine against polio, the immunoglobulin he used came from bovine colostrum.[60] When antibiotics began to appear, interest in colostrum waned, but, now that antibiotic-resistant strains of pathogens have developed, interest is once again returning to natural alternatives to antibiotics, namely, colostrum.[61]
Although bovine colostrum has been consumed by humans for centuries,[62] only in recent decades have we seen an increase in randomized clinical trials to support assertions of health benefits. It is probable that little absorption of intact growth factors and antibodies into the bloodstream occurs, due to digestion in the gastrointestinal tract. However, the presence of casein and other buffering proteins does allow growth factors and other bioactive molecules to pass into the lumen of the small intestine intact, where they can stimulate repair and inhibit microbes, working via local effects.[63] This provides a probable mechanism explaining reductions in gut permeability after colostrum administration in some published studies,[64][65][66] while another study found colostrum promising as treatment for distal colitis.[67] Evidence for the beneficial effect of colostrum on extra-gastrointestinal problems is less well developed, due in part to the limited number of randomised double-blind studies published, although a variety of possible uses have been suggested.[68][69][70]
The gut plays several important roles including acting as the main pathway for fluid, electrolyte and nutrient absorption while also acting as a barrier to toxic agents present in the gut lumen including acid, digestive enzymes and gut bacteria. It is also a major immunological defence mechanism, detecting natural commensals and triggering immune response when toxic microbes are present. Failure of homeostasis due to trauma, drugs and infectious microbes not only damages the gut but can lead to influx of damaging agents into the bloodstream. These mechanisms have relevance for multiple conditions affecting all areas of the world and socioeconomic groups such as ulcers, inflammation, and infectious diarrhea.[71] There is currently much interest in the potential value of colostrum for the prevention and treatment of these conditions as it is derived from natural sources and can influence damaging factors through multiple pathways including nutritional support, immunological intervention (through its immunoglobulin and other anti-microbial factors) and growth/healing factor constituents.[72] As pointed out by Kelly, inconsistency between results in some published studies may be due in part to variation in dose given and to the timing of the colostrum collection being tested (first milking versus pooled colostrum collected up to day 5 following calving).[73]
Some athletes have used colostrum in an attempt to improve their performance,[74] decrease recovery time,[47] and prevent sickness during peak performance levels.[75][76] Supplementation with bovine colostrum, 20 grams per day (g/d), in combination with exercise training for eight weeks may increase bone-free lean body mass in active men and women.[74][77]
Low IGF-1 levels may be associated with dementia in the very elderly, although causation has not been established.[78] Malnutrition can cause low levels of IGF-1,[79] as can obesity.[80] Supplementation with colostrum, which is rich in IGF-1, can be a useful part of a weight reduction program. Although IGF-1 is not absorbed intact by the body, some studies suggest it stimulates the production of IGF-1 when taken as a supplement[81] whereas others do not.[49]
Colostrum also has antioxidant components, such as lactoferrin[82] and hemopexin, which binds free heme in the body.[83]
The Isle of Man had a local delicacy called "Groosniuys", a pudding made with colostrum.[84] In Finland, a baked cheese called Leipäjuusto is traditionally made with either cow colostrum or reindeer milk.
A sweet cheese-like delicacy called 'Junnu' or 'Ginna' is made with colostrum in the south Indian states of Karnataka, Andhra Pradesh and Telangana. It is made with both cow and buffalo milk; in both cases it is the milk produced on the second day after giving birth which is considered best for making this pudding-like delicacy. Colostrum is in very high demand in these states, resulting in product adulteration.[85]
Hyperimmune colostrum
Hyperimmune colostrum is natural bovine colostrum collected from a population of cows immunized repeatedly with a specific pathogen. The colostrum is collected within 24 hours of the cow giving birth. Antibodies towards the specific pathogens or antigens that were used in the immunization are present in higher levels than in the population before treatment. Although some papers have been published stating that specific human pathogens were just as high as in hyperimmune colostrum, and natural colostrum nearly always had higher antibody titers than did the hyperimmune version.[59] Clinical trials[86] have shown that if the immunization is by surface antigens of the bacteria, the Bovine Colostrum Powder [87] can be used to make tablets capable of binding to the bacteria so that they are excreted in stools. This prevents the successful colonization of the gut, which would otherwise lead to bacteria releasing enterotoxigenic materials.
Proline-rich polypeptides
These small immune signaling peptides (PRPs) were independently discovered in colostrum and other sources, such as blood plasma, in the United States,[88] Czechoslovakia and Poland.[89] Hence they appear under various names in the literature, including Colostrinin, CLN, transfer factor and PRP. They function as signal transducing molecules that have the unique effect of modulating the immune system, turning it up when the body comes under attack from pathogens or other disease agents, and damping it when the danger is eliminated or neutralized.[90] At first thought to actually transfer immunity from one immune system to another, it now appears that PRPs simply stimulate cell-mediated immunity.[91]
References
- Ballard, Olivia; Morrow, Ardythe L. (February 2013). "Human Milk Composition". Pediatric Clinics of North America. 60 (1): 49–74. doi:10.1016/j.pcl.2012.10.002. PMC 3586783. PMID 23178060.
- "Beestings". Retrieved 29 December 2022.
- Sangild, P. T.; Thymann, T.; Schmidt, M.; Stoll, B.; Burrin, D. G.; Buddington, R. K. (1 October 2013). "Invited Review: The preterm pig as a model in pediatric gastroenterology". Journal of Animal Science. 91 (10): 4713–4729. doi:10.2527/jas.2013-6359. PMC 3984402. PMID 23942716.
- Newburg, David S.; Walker, W. Allan (January 2007). "Protection of the Neonate by the Innate Immune System of Developing Gut and of Human Milk". Pediatric Research. 61 (1): 2–8. doi:10.1203/01.pdr.0000250274.68571.18. PMID 17211132. S2CID 22878097.
- Stelwagen, K.; Carpenter, E.; Haigh, B.; Hodgkinson, A.; Wheeler, T. T. (1 April 2009). "Immune components of bovine colostrum and milk1". Journal of Animal Science. 87 (suppl_13): 3–9. doi:10.2527/jas.2008-1377. PMID 18952725.
- Rathe, Mathias; Müller, Klaus; Sangild, Per Torp; Husby, Steffen (April 2014). "Clinical applications of bovine colostrum therapy: a systematic review". Nutrition Reviews. 72 (4): 237–254. doi:10.1111/nure.12089. PMID 24571383.
- Kaplan, Merve; Arslan, Ayşenur; Duman, Hatice (2022). "Production of Bovine Colostrum for Human Consumption to Improve Health". Frontiers in Pharmacology. 12: 796824. doi:10.3389/fphar.2021.796824. PMC 8762312. PMID 35046820.
- "Colostrum harvesting" (PDF). Retrieved 29 December 2022.
- "It's Only Natural". 2017-06-09.
- Bertotto, A.; Castellucci, G.; Fabietti, G.; Scalise, F.; Vaccaro, R. (1 November 1990). "Lymphocytes bearing the T cell receptor gamma delta in human breast milk". Archives of Disease in Childhood. 65 (11): 1274–1275. doi:10.1136/adc.65.11.1274-a. PMC 1792611. PMID 2147370.
- Groves, M. L. (1960). "The isolation of a red protein from milk". Journal of the American Chemical Society. 82 (13): 3345–3360. doi:10.1021/ja01498a029.
- Paulík S, Slanina L, Polácek M (January 1985). "Lyzozým v kolostre a krvnom sére teliat a dojníc" [Lysozyme in the colostrum and blood of calves and dairy cows]. Veterinární medicína (Praha) (in Slovak). 30 (1): 21–28. PMID 3918380.
- Reiter, Bruno (2008). "The Lactoperoxidase-Thiocyanate-Hydrogen Peroxide Antibacterium System". Ciba Foundation Symposium 65 – Oxygen Free Radicals and Tissue Damage. Novartis Foundation Symposia. pp. 285–294. doi:10.1002/9780470715413.ch16. ISBN 978-0-470-71541-3. PMID 225143.
- Brock, J. H.; et al. (1975). "Bactericidal and hemolytic activity of complement in bovine colostrum and serum: effect of proteolytic enzymes and ethylene glycol tetraacetic acid (EGTA)". Annales d'Immunologie. 126C (4): 439–451. PMID 813560.
- Zabłocka A, Janusz M, Rybka K, Wirkus-Romanowska I, Kupryszewski G, Lisowski J (2001). "Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs". European Cytokine Network. 12 (3): 462–7. PMID 11566627.
- Hagiwara K, Kataoka S, Yamanaka H, Kirisawa R, Iwai H (October 2000). "Detection of cytokines in bovine colostrum". Veterinary Immunology and Immunopathology. 76 (3–4): 183–90. doi:10.1016/S0165-2427(00)00213-0. PMID 11044552.
- Rudloff HE, Schmalstieg FC, Mushtaha AA, Palkowetz KH, Liu SK, Goldman AS (January 1992). "Tumor necrosis factor-alpha in human milk". Pediatric Research. 31 (1): 29–33. doi:10.1203/00006450-199201000-00005. PMID 1375729.
- Maheshwari A, Christensen RD, Calhoun DA (November 2003). "ELR+ CXC chemokines in human milk". Cytokine. 24 (3): 91–102. doi:10.1016/j.cyto.2003.07.002. PMID 14581003.
- Xu RJ (1996). "Development of the newborn GI tract and its relation to colostrum/milk intake: a review". Reprod. Fertil. Dev. 8 (1): 35–48. doi:10.1071/RD9960035. PMID 8713721.
- O'Dell SD, Day IN (July 1998). "Insulin-like growth factor II (IGF-II)". The International Journal of Biochemistry & Cell Biology. 30 (7): 767–71. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981.
- Okada M, Ohmura E, Kamiya Y, et al. (1991). "Transforming growth factor (TGF)-alpha in human milk". Life Sciences. 48 (12): 1151–1156. doi:10.1016/0024-3205(91)90452-H. PMID 2002746.
- Saito S, Yoshida M, Ichijo M, Ishizaka S, Tsujii T (October 1993). "Transforming growth factor-beta (TGF-beta) in human milk". Clinical and Experimental Immunology. 94 (1): 220–224. doi:10.1111/j.1365-2249.1993.tb06004.x. PMC 1534356. PMID 8403511.
- Tokuyama Y, Tokuyama H (February 1993). "Purification and identification of TGF-beta 2-related growth factor from bovine colostrum". Journal of Dairy Research. 60 (1): 99–109. doi:10.1017/S0022029900027382. PMID 8436667. S2CID 38562131.
- Hironaka, T.; Ohishi, H.; Masaki, T. (March 1997). "Identification and Partial Purification of a Basic Fibroblast Growth Factor-Like Growth Factor Derived from Bovine Colostrum". Journal of Dairy Science. 80 (3): 488–495. doi:10.3168/jds.S0022-0302(97)75961-7. PMID 9098798.
- Xiao X, Xiong A, Chen X, Mao X, Zhou X (March 2002). "Epidermal growth factor concentrations in human milk, cow's milk and cow's milk-based infant formulas". Chinese Medical Journal. 115 (3): 451–454. PMID 11940387.
- Playford RJ, Macdonald CE, Johnson WS (July 2000). "Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders". American Journal of Clinical Nutrition. 72 (1): 5–14. doi:10.1093/ajcn/72.1.5. PMID 10871554.
- Vuorela P, Andersson S, Carpén O, Ylikorkala O, Halmesmäki E (November 2000). "Unbound vascular endothelial growth factor and its receptors in breast, human milk, and newborn intestine". American Journal of Clinical Nutrition. 72 (5): 1196–201. doi:10.1093/ajcn/72.5.1196. PMID 11063449.
- Flidel-Rimon O, Roth P (November 1997). "Effects of milk-borne colony stimulating factor-1 on circulating growth factor levels in the newborn infant". Journal of Pediatrics. 131 (5): 748–50. doi:10.1016/S0022-3476(97)70105-7. PMID 9403658.
- Thapa, B. R. (2005-07-01). "Health factors in colostrum". The Indian Journal of Pediatrics. 72 (7): 579–581. doi:10.1007/BF02724182. ISSN 0973-7693. PMID 16077241. S2CID 24277138.
- "The Phases of Breast Milk | WIC Breastfeeding Support". wicbreastfeeding.fns.usda.gov. Retrieved 29 December 2022.
- Buescher, E. S.; McIlheran, S. M. (July 1988). "Antioxidant Properties of Human Colostrum". Pediatric Research. 24 (1): 14–19. doi:10.1203/00006450-198807000-00005. ISSN 1530-0447. PMID 2842722. S2CID 2334728.
- Goldblum, R. M.; Ahlstedt, S.; Carlsson, B.; Hanson, L. Å; Jodal, U.; Lidin-Janson, G.; Sohl-Åkerlund, A. (October 1975). "Antibody-forming cells in human colostrum after oral immunisation". Nature. 257 (5529): 797–799. Bibcode:1975Natur.257..797G. doi:10.1038/257797a0. ISSN 1476-4687. PMID 1102990. S2CID 4148015.
- "Bovine Colostrum: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews". www.webmd.com. Retrieved 29 December 2022.
- McGrath, Brian A.; Fox, Patrick F.; McSweeney, Paul L. H.; Kelly, Alan L. (March 2016). "Composition and properties of bovine colostrum: a review". Dairy Science & Technology. 96 (2): 133–158. doi:10.1007/s13594-015-0258-x. S2CID 83925224.
- Ulfman, Laurien H.; Leusen, Jeanette H. W.; Savelkoul, Huub F. J.; Warner, John O.; van Neerven, R. J. Joost (22 June 2018). "Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection". Frontiers in Nutrition. 5: 52. doi:10.3389/fnut.2018.00052. PMC 6024018. PMID 29988421.
- Cesarone, Maria Rosaria; Belcaro, Gianni; Di Renzo, Andrea; Dugall, Mark; Cacchio, Marisa; Ruffini, Irma; Pellegrini, Luciano; Del Boccio, Gilberto; Fano, Filiberto; Ledda, Andrea; Bottari, Angelica; Ricci, Andrea; Stuard, Stefano; Vinciguerra, Giulia (April 2007). "Prevention of Influenza Episodes With Colostrum Compared With Vaccination in Healthy and High-Risk Cardiovascular Subjects: The Epidemiologic Study in San Valentino". Clinical and Applied Thrombosis/Hemostasis. 13 (2): 130–136. doi:10.1177/1076029606295957. PMID 17456621. S2CID 22882696.
- Saad, Khaled; Abo-Elela, Mohamed Gamil M.; El-Baseer, Khaled A. Abd; Ahmed, Ahmed E.; Ahmad, Faisal-Alkhateeb; Tawfeek, Mostafa S. K.; El-Houfey, Amira A.; Aboul_Khair, Mohamed Diab; Abdel-Salam, Ahmad M.; Abo-elgheit, Amir; Qubaisy, Heba; Ali, Ahmed M.; Abdel-Mawgoud, Eman (September 2016). "Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children". Medicine. 95 (37): e4560. doi:10.1097/MD.0000000000004560. PMC 5402550. PMID 27631207.
- Filipescu, Iulia Elena; Leonardi, Leonardo; Menchetti, Laura; Guelfi, Gabriella; Traina, Giovanna; Casagrande-Proietti, Patrizia; Piro, Federica; Quattrone, Alda; Barbato, Olimpia; Brecchia, Gabriele (23 August 2018). "Preventive effects of bovine colostrum supplementation in TNBS-induced colitis in mice". PLOS ONE. 13 (8): e0202929. Bibcode:2018PLoSO..1302929F. doi:10.1371/journal.pone.0202929. PMC 6107273. PMID 30138385.
- Watson, Ronald Ross; Collier, Robert J.; Preedy, Victor R. (2017). Dairy in Human Health and Disease across the Lifespan. Academic Press. ISBN 978-0-12-809869-1.
- Playford, R (June 2001). "Peptide therapy and the gastroenterologist: colostrum and milk-derived growth factors". Clinical Nutrition. 20: 101–106. doi:10.1054/clnu.2001.0434.
- Barakat, Sana Hosny; Meheissen, Marwa Ahmed; Omar, Omneya Magdy; Elbana, Doaa Ali (5 June 2019). "Bovine Colostrum in the Treatment of Acute Diarrhea in Children: A Double-Blinded Randomized Controlled Trial". Journal of Tropical Pediatrics. 66 (1): 46–55. doi:10.1093/tropej/fmz029. PMID 31168590.
- Patel, Kamlesh; Rana, Rajiv (July 2006). "Pedimune in recurrent respiratory infection and diarrhoea—The Indian experience—The PRIDE study". The Indian Journal of Pediatrics. 73 (7): 585–591. doi:10.1007/BF02759923. PMID 16877852. S2CID 26464312.
- Pakkanen, R.; Aalto, J. (May 1997). "Growth factors and antimicrobial factors of bovine colostrum". International Dairy Journal. 7 (5): 285–297. doi:10.1016/S0958-6946(97)00022-8.
- Gopal, Pramod K.; Gill, H. S. (November 2000). "Oligosaccharides and glycoconjugates in bovine milk and colostrum". British Journal of Nutrition. 84 (S1): 69–74. doi:10.1017/s0007114500002270. PMID 11242449.
- Mehra R, Sing R, Kumar N, et al. UGC Sponsored National Conference on Food Safety, Nutritional Security and Sustainability. 2020. ISBN 978-81-942875-0-
- Huppertz, Hans-Iko; Rutkowski, Stefan; Busch, Dirk H.; Eisebit, Reinhard; Lissner, Reinhard; Karch, Helge (October 1999). "Bovine Colostrum Ameliorates Diarrhea in Infection with Diarrheagenic Escherichia coli, Shiga Toxin-Producing E. coli, and E. coli Expressing Intimin and Hemolysin". Journal of Pediatric Gastroenterology & Nutrition. 29 (4): 452–456. doi:10.1097/00005176-199910000-00015. PMID 10512407.
- Buckley, J. D.; Abbott, M. J.; Brinkworth, G. D.; Whyte, P. B. D. (June 2002). "Bovine colostrum supplementation during endurance running training improves recovery, but not performance". Journal of Science and Medicine in Sport. 5 (2): 65–79. doi:10.1016/s1440-2440(02)80028-7. PMID 12188088.
- Brinkworth, Grant D.; Buckley, Jonathan D.; Slavotinek, John P.; Kurmis, Andrew P. (1 January 2004). "Effect of bovine colostrum supplementation on the composition of resistance trained and untrained limbs in healthy young men". European Journal of Applied Physiology. 91 (1): 53–60. doi:10.1007/s00421-003-0944-x. PMID 14504943. S2CID 35803322.
- Duff, Whitney R. D.; Chilibeck, Philip D.; Rooke, Julianne J.; Kaviani, Mojtaba; Krentz, Joel R.; Haines, Deborah M. (June 2014). "The Effect of Bovine Colostrum Supplementation in Older Adults During Resistance Training". International Journal of Sport Nutrition and Exercise Metabolism. 24 (3): 276–285. doi:10.1123/ijsnem.2013-0182. PMID 24281841.
- Kotsis, Yiannis; Mikellidi, Anastasia; Aresti, Cleopatra; Persia, Eleni; Sotiropoulos, Aristomenis; Panagiotakos, Demosthenes B.; Antonopoulou, Smaragdi; Nomikos, Tzortzis (April 2018). "A low-dose, 6-week bovine colostrum supplementation maintains performance and attenuates inflammatory indices following a Loughborough Intermittent Shuttle Test in soccer players". European Journal of Nutrition. 57 (3): 1181–1195. doi:10.1007/s00394-017-1401-7. PMC 5861165. PMID 28285432.
- Houser, B. A. (2008). "A Survey of Bacteriological Quality and the Occurrence of Salmonella in Raw Bovine Colostrum". Foodborne Pathogens and Disease. 5 (6): 853–858. doi:10.1089/fpd.2008.0141. PMID 18991543 – via Researchgate.net.
- Dominguez, E.; Perez, M. D.; Calvo, M. (1997). "Effect of heat treatment on the antigen-binding activity of anti-peroxidase immunoglobulins in bovine colostrum". Journal of Dairy Science. 80 (12): 3182–3187. doi:10.3168/jds.S0022-0302(97)76290-8. ISSN 0022-0302. PMID 9436097.
- Balfour, W. E.; Comline, R. S. (1 February 1962). "Acceleration of the absorption of unchanged globulin in the new-born calf by factors in colostrum". The Journal of Physiology. 160 (2): 234–257. doi:10.1113/jphysiol.1962.sp006844. PMC 1359530. PMID 16992118.
- Bush, L. J.; Staley, T. E. (April 1980). "Absorption of Colostral Immunoglobulins in Newborn Calves". Journal of Dairy Science. 63 (4): 672–680. doi:10.3168/jds.S0022-0302(80)82989-4. PMID 6991559.
- Staley, T. E.; Bush, L. J. (January 1985). "Receptor Mechanisms of the Neonatal Intestine and Their Relationship to Immunoglobulin Absorption and Disease". Journal of Dairy Science. 68 (1): 184–205. doi:10.3168/jds.S0022-0302(85)80812-2. PMID 3884680.
- Jensen, Annette R.; Elnif, Jan; Burrin, Douglas G.; Sangild, Per T. (1 December 2001). "Development of Intestinal Immunoglobulin Absorption and Enzyme Activities in Neonatal Pigs Is Diet Dependent". The Journal of Nutrition. 131 (12): 3259–3265. doi:10.1093/jn/131.12.3259. PMID 11739877.
- Sawyer M, Willadsen CH, Osburn BI, McGuire TC (15 December 1977). "Passive transfer of colostral immunoglobulins from ewe to lamb and its influence on neonatal lamb mortality". Journal of the American Veterinary Medical Association. 171 (12): 1255–9. PMID 604324.
- Pakkanen R, Aalto J (1997). "Growth Factors and Antimicrobial Factors of Bovine Colostrum". International Dairy Journal. 7 (5): 285–297. doi:10.1016/S0958-6946(97)00022-8.
- McConnell, Michelle A.; Buchan, Glenn; Borissenko, Michail V.; Brooks, Heather J. L. (2001). "A comparison of IgG and IgG1 activity in an early milk concentrate from non-immunised cows and a milk from hyperimmunised animals". Food Research International. 34 (2–3): 255–261. doi:10.1016/S0963-9969(00)00163-0.
- Sabin, A. B. (November 1950). "Antipoliomyelitic substance in milk of human beings and certain cows". A.M.A. American Journal of Diseases of Children. 80 (5): 866–7. PMID 14777169.
- Pallasch, Thomas J. (October 2003). "Antibiotic prophylaxis: problems in paradise". Dental Clinics of North America. 47 (4): 665–679. doi:10.1016/s0011-8532(03)00037-5. PMID 14664458.
- Buttar, Harpal S.; Bagwe, Siddhi M.; Bhullar, Sukhwinder K.; Kaur, Ginpreet (2017). "Health Benefits of Bovine Colostrum in Children and Adults". Dairy in Human Health and Disease Across the Lifespan. pp. 3–20. doi:10.1016/B978-0-12-809868-4.00001-7. ISBN 978-0-12-809868-4.
- Playford, R. J.; Woodman, A. C.; Vesey, D.; Deprez, P. H.; Calam, J.; Watanapa, P.; Williamson, R. C. N.; Clark, P. (April 1993). "Effect of luminal growth factor preservation on intestinal growth". The Lancet. 341 (8849): 843–848. doi:10.1016/0140-6736(93)93057-8. PMID 8096559. S2CID 30904879.
- Davison, Glen; Marchbank, Tania; March, Daniel S.; Thatcher, Rhys; Playford, Raymond J. (August 2016). "Zinc carnosine works with bovine colostrum in truncating heavy exercise–induced increase in gut permeability in healthy volunteers". The American Journal of Clinical Nutrition. 104 (2): 526–536. doi:10.3945/ajcn.116.134403. PMID 27357095.
- Marchbank, Tania; Davison, Glen; Oakes, Jemma R.; Ghatei, Mohammad A.; Patterson, Michael; Moyer, Mary Pat; Playford, Raymond J. (March 2011). "The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes". American Journal of Physiology. Gastrointestinal and Liver Physiology. 300 (3): G477–G484. doi:10.1152/ajpgi.00281.2010. PMID 21148400. S2CID 1829471.
- Playford, Raymond J.; Macdonald, Christopher E.; Calnan, Denis P.; Floyd, David N.; Podas, Theo; Johnson, Wendy; Wicks, Anthony C.; Bashir, O.; Marchbank, Tania (1 June 2001). "Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability". Clinical Science. 100 (6): 627–633. doi:10.1042/cs1000627. PMID 11352778. S2CID 24586050.
- Khan, Z.; Macdonald, C.; Wicks, A. C.; Holt, M. P.; Floyd, D.; Ghosh, S.; Wright, N. A.; Playford, R. J. (November 2002). "Use of the 'nutriceutical', bovine colostrum, for the treatment of distal colitis: results from an initial study". Alimentary Pharmacology & Therapeutics. 16 (11): 1917–1922. doi:10.1046/j.1365-2036.2002.01354.x. PMID 12390100. S2CID 30564496.
- Uruakpa, F.; Ismond, M. A. H.; Akobundu, E. N. T. (2002). "Colostrum and its benefits: a review". Nutrition Research. 22 (6): 755–767. doi:10.1016/S0271-5317(02)00373-1.
- Playford, R. J.; Floyd, D. N.; Macdonald, C. E.; Calnan, D. P.; Adenekan, R. O.; Johnson, W.; Goodlad, R. A.; Marchbank, T. (May 1999). "Bovine colostrum is a health food supplement which prevents NSAID induced gut damage". Gut. 44 (5): 653–658. doi:10.1136/gut.44.5.653. PMC 1727496. PMID 10205201.
- Carver, J. D.; Barness, L. A. (June 1996). "Trophic factors for the gastrointestinal tract". Clinics in Perinatology. 23 (2): 265–285. doi:10.1016/S0095-5108(18)30242-2. PMID 8780905.
- Baumgart, Daniel C.; Dignass, Axel U. (November 2002). "Intestinal barrier function". Current Opinion in Clinical Nutrition and Metabolic Care. 5 (6): 685–694. doi:10.1097/00075197-200211000-00012. PMID 12394645. S2CID 2326543.
- Playford, Raymond J.; Macdonald, Christopher E.; Johnson, Wendy S. (1 July 2000). "Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders". The American Journal of Clinical Nutrition. 72 (1): 5–14. doi:10.1093/ajcn/72.1.5. PMID 10871554.
- Kelly, G. S. (November 2003). "Bovine colostrums: a review of clinical uses". Alternative Medicine Review. 8 (4): 378–394. PMID 14653766.
- Hofman, Zandrie; Smeets, Rolf; Verlaan, George; Lugt, Richard V. D.; Verstappen, Peter A. (December 2002). "The Effect of Bovine Colostrum Supplementation on Exercise Performance in Elite Field Hockey Players". International Journal of Sport Nutrition and Exercise Metabolism. 12 (4): 461–469. doi:10.1123/ijsnem.12.4.461. PMID 12500989.
- Playford, Ray; et al. (March 2011). "The nutriceutical, bovine colostrum, truncates the increase in gut permeability caused by heavy exercise in athletes". American Journal of Physiology. Gastrointestinal and Liver Physiology. 300 (3): G477-84. doi:10.1152/ajpgi.00281.2010. PMID 21148400.
- Berk, L. S.; Nieman, D. C.; Youngberg, W. S.; Arabatzis, K.; Simpson-Westerberg, M.; Lee, J. W.; Tan, S. A.; Eby, W. C. (April 1990). "The effect of long endurance running on natural killer cells in marathoners". Medicine and Science in Sports and Exercise. 22 (2): 207–212. PMID 2355818.
- Antonio, Jose; Sanders, Michael S.; Van Gammeren, Darin (March 2001). "The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women". Nutrition. 17 (3): 243–247. doi:10.1016/s0899-9007(00)00552-9. PMID 11312068.
- Arai, Y.; Hirose, N.; Yamamura, K.; Shimizu, K.-i.; Takayama, M.; Ebihara, Y.; Osono, Y. (1 February 2001). "Serum Insulin-like Growth Factor-1 in Centenarians: Implications of IGF-1 as a Rapid Turnover Protein". The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 56 (2): M79–M82. doi:10.1093/gerona/56.2.m79. PMID 11213280.
- Caregaro, L.; Favaro, A.; Santonastaso, P.; Alberino, F.; Di Pascoli, L.; Nardi, M.; Favaro, S.; Gatta, A. (June 2001). "Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders". Clinical Nutrition. 20 (3): 251–257. doi:10.1054/clnu.2001.0397. PMID 11407872.
- Rasmussen, Michael Højby; Frystyk, Jan; Andersen, Teis; Breum, Leif; Christiansen, Jens Sandahl; Hilsted, Jannik (March 1994). "The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone". Metabolism. 43 (3): 315–319. doi:10.1016/0026-0495(94)90099-x. PMID 7511202.
- Mero, Antti; Kähkönen, Jonne; Nykänen, Tarja; Parviainen, Tapani; Jokinen, Ilmari; Takala, Timo; Nikula, Tuomo; Rasi, Simo; Leppäluoto, Juhani (1 August 2002). "IGF-I, IgA, and IgG responses to bovine colostrum supplementation during training". Journal of Applied Physiology. 93 (2): 732–739. doi:10.1152/japplphysiol.00002.2002. PMID 12133885. S2CID 10568424.
- Wakabayashi, Hiroyuki; Matsumoto, Hiroshi; Hashimoto, Koichi; Teraguchi, Susumu; Takase, Mitsunori; Hayasawa, Hirotoshi (January 1999). "Inhibition of Iron/Ascorbate-Induced Lipid Peroxidation by an N-Terminal Peptide of Bovine Lactoferrin and Its Acylated Derivatives". Bioscience, Biotechnology, and Biochemistry. 63 (5): 955–957. doi:10.1271/bbb.63.955. PMID 10380640.
- Gutteridge, J. M.; Smith, A. (15 December 1988). "Antioxidant protection by haemopexin of haem-stimulated lipid peroxidation". Biochemical Journal. 256 (3): 861–865. doi:10.1042/bj2560861. PMC 1135495. PMID 3223958.
- "Cooking and Food" (PDF). Manx Farming and Country Life. 9. 1991. Archived from the original (PDF) on 2010-02-15. Retrieved 2017-08-03.
- K., Bhumika (2017-05-18). "The milky way". The Hindu. Retrieved 2021-04-21.
- Otto, Wlodzimierz; Najnigier, Boguslaw; Stelmasiak, Teodor; Robins-Browne, Roy M. (July 2011). "Randomized control trials using a tablet formulation of hyperimmune bovine colostrum to prevent diarrhea caused by enterotoxigenic Escherichia coli in volunteers". Scandinavian Journal of Gastroenterology. 46 (7–8): 862–868. doi:10.3109/00365521.2011.574726. PMC 3154584. PMID 21526980.
- TGA guidance BCP
- Lawrence, H. S. (1 August 1949). "The Cellular Transfer of Cutaneous Hypersensitivity to Tuberculin in Man". Experimental Biology and Medicine. 71 (4): 516–522. doi:10.3181/00379727-71-17242. PMID 18139800. S2CID 37728884.
- Janusz, Maria; Lisowski, Józef; Franěk, Frantisěk (15 December 1974). "Isolation and characterization of a proline-rich polypeptide from ovine colostrum". FEBS Letters. 49 (2): 276–279. doi:10.1016/0014-5793(74)80529-6. PMID 4442608. S2CID 2495375.
- Zimecki, Michal (2008). "A Proline-Rich Polypeptide from Ovine Colostrum: Colostrinin with Immunomodulatory Activity". Bioactive Components of Milk. Advances in Experimental Medicine and Biology. Vol. 606. pp. 241–250. doi:10.1007/978-0-387-74087-4_9. ISBN 978-0-387-74086-7. PMID 18183932.
- Levin, A. S.; Spitler, L. E.; Fudenberg, H. H. (1975). "Transfer factor I: methods of therapy". Birth Defects Original Article Series. 11 (1): 445–448. PMID 1080060.