Following are References to Papers Relating to the Efficacy of Colostrum*:

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Allergies

Buescher, ES, McWilliams-Koeppen, P. Soluble tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk bind to TNF-alpha and neutralize TNF-alpha bioactivity. Pediatric Research 44(1):37-42 (1998). The ability of colostrum to modulate the inflammatory response is unique. One of the ways in which it does this is through TNF-a receptor proteins, which are found in colostrum. These bind to TNF-a, which inactivates the TNF-a. TNF-a is the activator of the entire inflammatory cascade, so by controlling its activity, colostrum controls the degree of the inflammatory response and can shut it off altogether.

Collins, AM, et al. Bovine milk, including pasteurized milk, contains antibodies directed against allergens of clinical importance to man. International Archives of Allergy and Applied Immunology 96:362-367 (1991). The presence of antibodies against many of the most common allergies in man, including ryegrass pollen, house dust mites, Aspergillus mold and wheat gluten, were detected in bovine colostrum.

Delespesse, G. Polypeptide factors from colostrum. US Patent #5,371,073 (1994). IgE (the immunoglobulin involved in allergic response) binding factors (IgE-bf) and IgE suppressor activity (IgE-SF) obtained from colostrum have been successfully used to treat allergies.

Elrod, KC, et al. Lactoferrin, a potent tryptase inhibitor, abolished late-phase airway responses in allergic sheep. American Journal of Respiratory Critical Care Medicine 156:375-381 (1997). Tryptase, a digestive enzyme, has been implicated in various aspects of asthma, including bronchoconstriction and airway hyperreactivity. Lactoferrin has been shown to inhibit tryptase activity, thus relieving the symptoms of asthma.

Goldman, AS, et al. Anti-inflammatory properties of human milk. Acta Paediatrica Scandinavica 75(5):689-695 (1986). The major anti-inflammatory components found in human milk (and bovine colostrum) include anti-proteases, lactoferrin, lysozyme, secretory IgA, and a number of antioxidants, including cysteine, ascorbate, alpha-tocopherol and beta-carotene.

Keech, A.M., Peptide Immunotherapy: The Use of Bovine Colostrum Proline-Rich Polypeptides in Cytokine Modulation for the Alternative Relief of Allergic Symptoms. 2007 AAAAI Annual Meeting, San Diego, February 23-27 (to be published).

LeFranc-Millot C, Vercaigne-Marko D, Wal J. -M, et al. (1996) Comparison of the IgE titers to bovine colostral G immunoglobulins and the F(ab')2 fragments in sera of patients allergic to milk. Int Arch Allergy Immunol. 110:156-162.

Murphey, DK, Buescher, ES. Human colostrum has anti-inflammatory activity in a rat subcutaneous air pouch model of inflammation. Pediatric Research 34(2):208-212 (1993). In an experimental animal model using subcutaneous air pouches in rats, colostrum showed significant anti-inflammatory activity.

Savilahti, E, Tainio, VM, Salmenpera, L, Arjomaa, P, Kallio, M, Perheentupa, J, Siimes, MA. Low colostral IgA associated with cow's milk allergy. Acta Paediatrica Scandinavica 80(12):1207-1213 (1991).

Savilahti E, Tainio VM, Salmenpera L, Arjomaa P, Kallio M, Perheentupa J, Siimes MA. (1991) Low colostral IgA associated with cow's milk allergy.Acta Pediatr Scan. 80:1207-1213.

Selo I, Clement G, Bernard H, et al. (1999) Allergy to bovine B-lactoglobulin: specificity of human IgE to tryptic peptides. Clinical and Experimental Allergy. 29:1055-1063.

Yoshioka, Y, Kudo, S, Nishimura, H, Yajima, T, Kishihara, K, Saito, K, Suzuki, T, Suzuki, Y, Kuroiwa, S, Yoshikai, Y. (2005) Oral administration of bovine colostrum stimulates intestinal intraepithelial lymphocytes to polarize Th1-type in mice. International Immunopharmacology 5(3):581-90. Stimulating the Th1 immune response from the Th2 skewed immune response in infancy is important to reduce the incidence of allergies. Mice given colostrum showed a polarization to Th1 response in intestinal intraepithelial lymphocytes while intestinal microflora and IgA levels showed no change. This suggests that colostrum may protect from both infectious disease and allergies mediated by Th2 type responses.

"Clinical studies show that IgE found in bovine colostrum, may be responsible for regulating allergic response," according to Drs. Tortora, Funke and Cast in Microbiology.

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Alzheimers

Amaducci, L, et al. Use of phosphatidylserine in Alzheimer's disease. Annals of the New York Academy of Science 640:245-249 (1991). Supplementation with phosphatidylserine, one of the phospholipids found in BIO-lipid, also produces an improvement in symptoms in Alzheimer's.

Amaducci L. (1988) Phosphatidylserine in the treatment of Alzheimer's disease: results of a multicenter study. Psychopharmacology Bulletin. 24(1):130-4.

Ames, BN, et al. Oxidants, antioxidants, and the degenerative diseases of aging. Proceedings of the National Academy of Sciences USA 90(17):7915-7922(1993). Oxidant by-products of metabolism cause significant damage to DNA, proteins and lipids. This damage results in aging and the degenerative diseases associated with aging, such as cancer, cardiovascular disease, immune system decline, brain dysfunction and cataracts. Antioxidant defenses against these diseases decline with age, necessitating the supplementation of antioxidants in the diet.

Bilikiewicz, A, Gaus, W. Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer's disease. Journal of Alzheimer’s Disease 6(1):17-26 (2004).

Crook, TH, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology 41(5):644-649 (1991). Patients with age-associated memory impairment showed significant improvement in memory performance tests with phosphatidylserine supplementation over a 12 week period.

Crook, T, et al. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacology Bulletin 28(1):61-66 (1992). Another study which showed an improvement in symptoms of Alzheimer's with phosphatidylserine supplementation over 12 weeks. The less the impairment, the greater the improvement, suggesting that the earlier phosphatidylserine supplementation is begun in the course of the disease, the better the results will be.

Cross, CE, et al. Oxygen radicals and human disease. Annals of Internal Medicine 107(4):526-545 (1987). Oxygen free radicals, the by-products of normal metabolism, have been implicated in disease processes ranging from carcinogenesis to aging, emphasizing the importance of antioxidants in combating these conditions.

Leszek, J, et al. Colostrinin: proline-rich polypeptide complex from ovine colostrum - a long-term study of its efficacy in Alzheimer's disease. Medical Science Monitor 8(10):P193-P196 (2002). In a longer-term study, colostrinin produced improvement or stabilization in patients involved in the study.

Leszek, J, Inglot, AD, Janusz, M, Lisowski, J, Krukowska, K, Georgiades, JA. Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study. Archivum immunologiae et therapiae experimentalis (Warszava) 47(6):377-385 (1999).

Leszek, J, Inglot, AD, Janusz, M, Byczkiewicz, F, Kiejna, A, Georgiades, J, Lisowski, J. Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term study of its efficacy in Alzheimer's disease. Medical Science Monitor 8(10):193-196 (2002).

Mikulska, JE, Lisowski, J. A proline-rich polypeptide complex (PRP) from ovine colostrum. Studies on the effect of PRP on nitric oxide (NO) production induced by LPS in THP-1 cells. Immunopharmacology and Immunotoxicology 25(4):645-654 (2003).

Popik, P, Bobula, B, Janusz, M, Lisowski, J, Vetulani, J. Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats. Pharmacology and Biochemistry of Behavior 64(1):183-189 (1999).

Popik, P, Galoch, Z, Janusz, M, Lisowski, J, Vetulani, J. Cognitive effects of Colostral-Val nonapeptide in aged rats. Behavioral Brain Research 118(2):201-208 (2001).

Stewart, MG, Banks, D. Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm. Neurobiology of Learning and Memory prepublication (2006).

Schuster, D, Rajendran, A, Hui, SW, Nicotera, T, Srikrishnan, T, Kruzel, ML. Protective effect of colostrinin on neuroblastoma cell survival is due to reduced aggregation of beta-amyloid. Neuropeptides 39(4):419-426 (2005).

Zablocka, A, Janusz, M, Macala, J, Lisowski, J. A proline-rich polypeptide complex and its nonapeptide fragment inhibit nitric oxide production induced in mice. Regulatory Peptides 125(1-3):35-39 (2005).

For Additional Links: www.scholar.google.com keywords: Colostrum, Alzheimer's

Anti-aging

Asthma

Anti-Inflammatory

Anti-Microbial (Moldoveanu, Zina, et al, "Antibacterial Properties of Milk; IgA_ Peroxidase-Lactoferrin Interactions" Annals of N.Y. Academy of Science, (1983) Vol. 409, 848-850.

Conneely, OM. Anti-inflammatory activities of lactoferrin. Journal of the American College of Nutrition 20(Suppl.5):389S-395S (2001). Lactoferrin inhibits dermal inflammatory cytokine production and acts as a potent anti-inflammatory protein at local sites of inflammation, including the respiratory and gastrointestinal tracts.

Borody, TJ, et al. Tunnel vision in the bowel. Center for Digestive Diseases (2001). Review of irritable bowel syndrome, including ulcerative colitis and Crohn's disease, and its etiology, including infective agents such as Shigella and Campylobacter. Infections of the gut are difficult to treat because no antimicrobial therapy is available that is effective against Clostridia spores. Only bovine colostrum has proven clinical efficacy in eradicating intestinal pathogens, such as rotavirus, and may help control the infections seen in chronic disorders such as irritable bowel syndrome due to the number of biologically active components in colostrum. The growth factors in colostrum help heal intestinal erosions and ulcerations. It also contains anti-inflammatory factors and is nutrient rich. Colostrum may be used alone or in combination with other anti-inflammatory and/or immune substances. Future research should focus on identifying immune strategies, novel delivery systems and identification of the bioactives in colostrum.

Britigan, BE, et al. The role of lactoferrin as an anti-inflammatory molecule. Advances in Experimental Medicine and Biology 357:143-156 (1994). While the role of lactoferrin in providing non-specific immunity is well documented, it also plays a role in the anti-inflammatory response through its antioxidant effect.

Kim, K. et al, "In Vitro and In Vivo Neutralizing Activity of Human Colostrum and Milk Against Purified Toxins A and B of Clostridium Difficle" Journal of Infectious Diseases (1984) Vol. 150 (1) 57-61.

McConnell, M.A.; Brooks, H.J.L.; Borissenko, M.B.; Buchan, G. A comparative study of immunoglobulin feels and anti-inflammatory activity in four milk products. Journal of Dairy Science. Publication forthcoming.

Playford, RJ, et al. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut 44:653-658 (1999). Although non-steroidal anti-inflammatory drugs (NSAIDs) are very effective in controlling joint pain in arthritis, their use also causes significant, and sometimes fatal, gastrointestinal damage. Supplementation with colostrum, however, significantly reduced and healed injury caused by NSAIDs.

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. Clinical Science 100:627-633 (2001). Another study by Dr. Playford on the ability of colostrum to prevent damage due to NSAID use. This study showed that colostrum also prevents an increase in gastrointestinal permeability due to NSAID use, whereas NSAID use alone without colostrum causes an increase in permeability.

Wada, N., et al, "Neutralizing Activity Against Clostridium Difficile Toxins in the Supernatant of Cultured Colostral Cells" Infectious Immunology (1980) Vol. 29, 545-550.

"Glycoproteins in bovine colostrum inhibit the attachment of the Helicobacter pylori bacteria that cause stomach ulcers. Colostrum contains significant amounts of interleukin-10, a strong inflammation inhibitory agent found significant in reducing inflammation in arthritic joints and injury areas," wrote Dr. Olle Hernell, from the University of Ulmea, Sweden, in Science magazine.

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Anti-Oxidant Properties

Ahmed, L, Islam, SN, Khan, MN, Huque, S, Ahsan, M. (2004) Antioxidant micronutrient profile (vitamin E, C, A, copper, zinc, iron) of colostrum: association with maternal characteristics. Journal of Tropical Pediatrics 50(6):357-8. Maternal characteristics had no influence on the profile of nutrient profile of antioxidants in colostrum.

Boldogh, I, et al. Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. Journal of Molecular Neuroscience 20(2):125-134 (2003). Colostrinin down regulates lipid peroxidation, inhibits glutathione depletion and reduces intracellular levels of reactive oxygen species (ROS). This is one more way that colostrum demonstrates antioxidant activity.

Borissenko, M. Glutathione: A powerful anti-oxidant found in colostrum. NZMP August 2002. Both glutathione and its chemical predecessors are present in large quantities in colostrum. As glutathione is not absorbed directly, glutathione production in the body can only be accomplished by supplementation with its antecedents, cystine, glycine and glutamic acid, all of which are abundant in colostrum.

Buescher, ES, McIlheran, SM. Antioxidant properties of human colostrum. Pediatric Research 24(1):14-19 (1988). Colostrum reduces ferricytochrome C in polymorphonuclear leucocytes (PMNs) and also disrupts other metabolic and enzymatic activities of PMNs which are crucial in PMN respiratory burst mediation of acute inflammation, showing that colostrum is a powerful antioxidant.

Buescher, ES, McIlheran, SM. Colostral antioxidants: separation and characterization of two activities in human colostrum. Journal of Pediatric Gastroenterology and Nutrition 14(1):47-56 (1992). Colostrum interferes with the production of PMN respiratory burst products in two ways, ascorbate and uric acid.

Kurz, DJ, et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. Journal of Cell Science 117:2417-2426 (2004). Oxidative stress due to the buildup of oxidization by-products has been linked to the onset of cell senescence in blood vessel lining cells by disrupting telomere integrity. Telomeres are the "tails" of the chromosomes, the length of which determine the number of cell divisions a cell can undergo before reaching its limit. Glutathione, a powerful natural antioxidant, is crucial in maintaining telomere integrity.

Satue-Gracia, MT, et al. Lactoferrin in infant formulas: effect on oxidation. Journal of Agriculture and Food Chemistry 48(10):4984-4990 (2000). Commercially modified infant formulas based on cow's milk have significantly less lactoferrin than whole milk, and soy formulas contain none, even though lactoferrin acts as an iron transporter protein. Adding lactoferrin to infant formulas results in the dual benefit of increased iron absorption and acts as an antioxidant and antimicrobial to extend the shelf life of the formulas.

Shigenaga, MK, et al. Oxidative damage and mitochondrial decay in aging. Proceedings of the National Academy of Sciences USA 91(23):10771-10778 (1994). The major source of oxidative damage are oxidants generated by mitochondria in the cells of the body. Mitochondrial function declines with age, including decreased membrane fluidity, proton leakage across the inner mitochondrial membrane, and decreases levels of cardiolipin, an important lipid which supports the functioning of proteins in the inner mitochondrial membrane.

Wakabayashi, H, et al. Inhibition of iron/ascorbate-induced lipid peroxidation by an N-terminal peptide of bovine lactoferrin and its acylated derivatives. Bioscience, Biotechnology, Biochemistry 63(5):955-957 (1999). Lactoferrin also plays an important antioxidant role in colostrum by preventing lipid peroxidation.

For Additional Links: www.scholar.google.com keywords: Colostrum, Anti-oxidants

Athletic Performance

Antonio, J, et al. The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women. Nutrition 17(3):243-247 (2001). Actively training male and female athletes were given colostrum supplementation or placebo for a period of 8 weeks. Subjects receiving colostrum but not placebo showed an increase in lean body mass.

Berk, LS, et al. The effect of long endurance running on natural killer cells in marathoners. Medicine and Science in Sports and Exercise 22(2):207-212 (1990). A significant decrease in natural killer cell populations were seen in marathon runners following three hours of maximal exercise with full recovery of pre-exercise levels by 21 hours. This correlated with increases in cortisol levels during exercise.

Bricker, D.S. Colostrum: implications for accelerated recovery in damaged muscle and cartilage,prevention of some pathogenic disease. The American Chiropractor.pp. 4&5, November 1991.

Brinkworth, GD, et al. Effect of bovine colostrum supplementation on the composition of resistance trained and untrained limbs in healthy young men. European Journal of Applied Physiology 9(11):53-60 (2004). Either bovine colostrum or whey protein were given to young men who were either in training or not in training. Those in the training group who received colostrum showed a significantly greater increase in both upper arm circumference and cross-sectional area compared to those receiving whey, while those who were not in training showed no change.

Buckley, JD, et al. Effect of bovine colostrum on anaerobic exercise performance and plasma insulin-like growth factor I. Journal of Sports Science 21(7):577-588 (2003). Athletes in training were given either bovine colostrum or placebo for 8 weeks. Those receiving colostrum showed a significant increase in peak anaerobic power over placebo.

Buckley, J., et al. "Oral supplementation with bovine colostrum increases vertical jump performance." Presented at 4th Annual Congress of the European College of Sports Science, Rome 14-17 July, 1999.

Burke, ER. Colostrum as an Athletic Enhancer and Help for AIDS. Nutrition Science News May, 1996. While leaky gut is of concern to everyone, it is particularly so for athletes who need to utilize all the nutrients they take in and prevent infection when their immune systems are impaired following exercise. Many athletes suffer irritable bowel syndrome as a result of incomplete digestion of protein supplements. The role of colostrum-derived insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-ß) in healing leaky gut are explored.

Butler AA, Yakar S, Gewolb IH, Karas M, Okubo Y, LeRoith D, Diabetes Branch, NIH, Bethesda, MD, Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology.Page 3, Comp Biochem Physiol B Biochem Mol Biol 1998 Sep; 121(1):19-26.

Clark J. (1996) Uses of creatine phosphate and creatine supplementation for the athlete. Scientific and Clinical Perspective (1996).

Crooks, C, et al. Bovine colostrum supplementation increases levels of s-IGA in distance runners: a study based on athletes in training for the 2002 Rotorua marathon. Unpublished research. Marathon runners in training were given bovine colostrum or placebo for 12 weeks in a double blind study. Those in the colostrum group showed significantly more secretory IgA (s-IgA) in their saliva than either the placebo group or sedentary controls. The colostrum group also reported a significantly lower rate of upper respiratory infections (URI) during this period.

Coombes JS, Conacher M, Austen SK, Marshall PA. "Dose effects of oral bovine colostrum on physical work capacity in cyclists."Med Sci Sports Exerc. 2002 Jul;34(7):1184-8. Related Articles, Links, Dose effects of oral bovine colostrum on physical work capacity in cyclists. School of Human Movement Studies, University of Queensland, St Lucia, Australia.

Liu JL, LeRoith D, Clinical Endocrinology Branch, NIDDKD, NIH, Bethesda, MD, Insulin-like growth factor I is essential for post-natal growth in response to growth hormone. Endocrinology 1999 Nov; 140(11):5178-84.

Hwa V, Oh Y, Rosenfeld RG, Dept. of Pediatrics, Oregon Health Sciences University, Portland, OR, The insulin-like growth factor binding protein (IGFBP) superfamily. Endocr Rev 1999 Dec; 20(6):761-87.

Hofman, Z, et al. The effect of bovine colostrum supplementation on exercise performance in elite field hockey players. International Journal of Sports Nutrition and Exercise Metabolism 12(4):461-469 (2002). Colostrum supplementation in elite field hockey players, both male and female, resulted in improved sprint performance over placebo.

Kasemkijwattana, C, et al. Use of growth factors to improve muscle healing after strain injury. Clinical Orthopedics 370:272-285 (2000). Muscle injuries, such as strains, are common in athletes. The use of growth factors, such as IGF-1, in treating such injuries is explored.

Kuipers, H, et al. Effects of oral bovine colostrum supplementation on serum insulin-like growth factor-I levels. Nutrition 18(7-8):165-172 (2002). A study for the International Olympic Committee showed no increase in blood IGF-1 or IGF-bp3 levels after 4 weeks time.

Liang, L, et al. [Effect of cytokines on repair of tendon injury] Zhongguo Xiufu Chongjian Waike Zazhi (Chinese) 14(5):283-285 (2000). Cytokines, such as the growth factors, can accelerate tendon repair.

Mero, A, et al. IGF-I, IgA, and IgG responses to bovine colostrum supplementation during training. Journal of Applied Physiology 93(2):732-739 (2002). Colostrum supplementation increases levels of IGF-1 and IgA in training athletes, but the IGF-1 in the colostrum is not absorbed intact.

Nieman, DC, et al. Complement and immunoglobulin levels in athletes and sedentary controls. International Journal of Sports Medicine 10(2):124-128 (1989). Blood levels of complements C3 and C4 but not immunoglobulins decreased during periods of rest, graded maximal exercise and recovery in marathon runners.

Nieman, DC, et al. Effects of long-endurance running on immune system parameters and lymphocyte function in experienced marathoners. International Journal of Sports Medicine 10(5):317-323 (1989). Marathon runners experience a disruption of normal immune function after running long distances, a condition which returns to normal levels following 21 hours of recovery.

Molloy, T, et al. The roles of growth factors in tendon and ligament healing. Sports Medicine 33(5):381-394 (2003). The roles of five different growth factors, IGF-1, TGF-ß, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), in healing tendon and ligament injuries is explored. Each plays a different but vital role in the process.

Mero A, et al. (1997) Effects of bovine colostrum supplementation on serum IGF-1, IgG, hormone, and saliva IgA during training. Journal of Applied Physiology. 83:1144-1151.

Sato, K, et al. Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis. Muscle & Nerve 28(3):355-372 (2003). IGF-1 can improve muscle regeneration in injured muscle.

Spagnoli A, Rosenfeld RG, Dept. of Pediatrics, Oregon Health Sciences University, Portland, OR, The mechanisms by which growth hormone brings about growth. The relative contributions of growth hormone and insulin-like growth factors. Endocrinol Metab Clin North Am 1996 Sep; (3):615-31.

Sparling PB, Nieman DC, O'Connor PJ. (1993) Selected scientific aspects of marathon racing: an update on fluid replacement, immune function, psychological factors and the gender difference. Sports Medicine. 15:116-132.

Sparling, PB, et al. Selected scientific aspects of marathon racing. An update on fluid replacement, immune function, psychological factors and the gender difference. Sports Medicine 15(2):116-132 (1993). Negative changes to the immune system during long distance running increase the chances of upper respiratory infections in these athletes for a period following exercise. Proper nutrition, adequate rest and appropriate recover between workouts as well as other measures can lessen the risk.

Wu, A.H. & Perryman, M.B. "Clinical applications of muscle enzymes and proteins." Curr Opin Rheumatol, 1992;4(6):815-820.

Zimecki, M, et al. Effect of a proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand black (NZB) mice. Archivum Immunologiae et Therapiae Experimentalis 39(5-6):461-467 (1991). Colostrinin (PRP) increased survival in mice susceptible to hemolytic anemia, an autoimmune disease. It is hypothesized the colostrinin induces suppressor cells which slow development of the disease. This suggests that colostrinin may have therapeutic value in treating autoimmune diseases.

For Additional Links: www.scholar.google.com keywords: Colostrum, Althetic Performance

Bacterial Infections

Bitzan, M.M.; Gold, B.D.; Philpott, D.J.; Huesca, M.; Sherman, P.M.; Karch, H.; Lissner, R.; Lingwood, C.A.; Karmali, M.A.; Inhibition of Helicobacter pylori and Helicobactor mustelae binding to lipid receptors by bovine colostrum. The Journal of Infectious Diseases. 177:955-961, April 1998.

Bitzan, MM, et al. Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid receptors by bovine colostrum. Journal of Infectious Disease 177(4):955-961 (1998). H. pylori and H. mustelae (a gastric pathogen of ferrets) are both bound by lipid receptors (phosphatidylethanolamine, gangliotetraosylceramide and gangliotriaosyl-ceramide) in the gut, allowing them to carry out their pathogenic activities. Bovine colostrum, however, was shown to prevent binding of the pathogens to these lipid receptors even though there was no detectable anti-H. pylori antibody activity in the colostrum.

Bolke E, Jehle PM, Hausmann F, Daubler A, Wiedeck H, Steinbach G, Storck M, Orth K., Shock. 2002 Jan;17(1):9-12. Related Articles, Links, Preoperative oral application of immunoglobulin-enriched colostrum milk and mediator response during abdominal surgery. Department of Surgery, University of Ulm, Germany.

Butler, J. E. Immunoglobulins of the Mammary Secretions. Chapter Five. in: Lactation: A Comprehensive Treatise. Vol. 3. Eds. B. L. Larson and V. R. Smith. pp. 217-252. Academic Press. New York. 1974.

Casswall, TH, et al. Bovine anti-Helicobacter pylori antibodies for oral immunotherapy. Scandinavian Journal of Gastroenterology 37(12):1380-1385 (2002). Bovine colostrum with high titers against H. pylori was given to H. pylori infected mice. Comparison of treated mice with control mice showed a 50-66% cure rate for H. pylori infection in treated mice. Binding studies also showed that the colostrum prevented binding of the H. pylori.

Christopher-Hennings, J., et al., lmmunocompromise in gnotobiotic pigs induced by verotoxin-producing Escherichia coli (Olll:NM). Infect. Immun. 1993. 61: p. 2304-2308.

da Costa, RS, et al. Characterization of iron, copper and zinc levels in the colostrum of mothers of term and pre-term infants before and after pasteurization. International Journal of Food Science and Nutrition 54(2):111-117 (2003). Milk samples were collected from mothers from day 1 to day 7 postpartum. Milk that was pasteurized showed some diminution of zinc, copper and iron levels, but not to a significant degree. Sufficient levels remained in the pasteurized milk to supply the needs of the new-born infants.

Doyle, P. S. Anti-Cryptosporiduim antibodies inhibit infectivity in vitro and in 9 vivo. Infection and Immunity 61(10):4079-4084. Oct. 1993.

Ellison, RT III, Giehl, TJ. Killing of gram-negative bacteria by lactoferrin and lysozyme. Journal of Clinical Investigation 88(4):1080-1091 (1991). Lactoferrin and lysozyme act together to kill gram-negative bacteria, such as Vibrio cholerae (cholera), Salmonella typhimurium (food poisoning) and Eschericia coli. The lactoferrin attaches to and destroys the cell wall of the bacteria, allowing the lysozyme to enter and lyse (burst) the organisms.

Fayer R, Perryman LE, Riggs MW.J Parasitol. 1989 Feb;75(1):151-3. Related Articles, Links, Hyperimmune bovine colostrum neutralizes Cryptosporidium sporozoites and protects mice against oocyst challenge. Zoonotic Diseases Laboratory, United States Department of Agriculture, Beltsville, Maryland 20705.

Flanigan T, Marshall R, Redman D, Kaetzel C, Ungar B. J Protozool. 1991 Nov-Dec;38(6):225S-227S. Related Articles, Links, In vitro screening of therapeutic agents against Cryptosporidium: hyperimmune cow colostrum is highly inhibitory. Department of Medicine, University Hospitals, Case Western Reserve University, Cleveland, OH.

Funatogawa K, Ide T, Kirikae F, Saruta K, Nakano M, Kirikae T. Microbiol Immunol. 2002;46(11):761-6. Related Articles, Links, Use of immunoglobulin enriched bovine colostrum against oral challenge with enterohaemorrhagic Escherichia coli O157:H7 in mice. Southern Direct Meat Products Inspection Office, Tochigi, Tochigi 328-0033, Japan.

Holloway, NM, et al. Serum immunoglobulin G concentrations in calves fed fresh and frozen colostrum. Journal of the American Veterinary Medicine Association 219(3):357-359 (2001). No significant difference was found between the IgG concentrations of fresh bovine colostrum and frozen and thawed bovine colostrum.

Ho, P.C., and Lawton, J.W.M. Human colostral cells: Phagocytosis and killing of E. Coli and C. Albicans. The Journal of Pediatrics. Vol. 93, No. 6, pp. 910-915.

Kim, K., et al., In vitro and in vivo neutralizing activity of human colostrum and milk against purified toxins A and B of Clostridium difficile. T. Infect. Dis. 1985. 150: p. 57-61.

Gopal, PK, and Gill, HS. Oligosaccharides and glycoconjugates in bovine milk and colostrum. British Journal of Nutrition 84(Suppl.1):S69-S74 (2000). Another way colostrum helps protect against infections is through the oligosaccharides and glycoconjugates it contains. These are complex sugars which compete for binding sites in the GI tract with pathogens.

Graczyk TK, Cranfield MR, Bostwick EF., J Parasitol. 2000 Jun;86(3):631-2. Related Articles, Links, Successful hyperimmune bovine colostrum treatment of Savanna monitors (Varanus exanthematicus) infected with Cryptosporidium sp. Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Huppertz HI, Rutkowski S, Busch DH, Eisebit R, Lissner R, Karch H., J Pediatr Gastroenterol Nutr. 1999 Oct;29(4):452-6 . Related Articles, Links, Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. Coli, and E. coli expressing intimin and hemolysin. Children's Hospital, The University of Wurzburg, Germany.

Korhonen, H, et al. Milk immunoglobulins and complement factors. British Journal of Nutrition 84(Suppl.1):S75-S80 (2000). Bovine colostrum contains three main classes of immunoglobulin IgG (IgG1 75% and IgG2), IgM and IgA, plus hemolytic and bactericidal complement. Complement is a complex group of proteins which act in concert with antibodies to inactivate and/or kill pathogens.

Korhonen, H, et al. Bactericidal effect of bovine normal and immune serum, colostrum and milk against Helicobacter pylori. Journal of Applied Bacteriology 78(6):655-662 (1995). Helicobacter pylori is a major cause of gastritis and ulcers in humans. Serum and colostrum from non-immunized Friesian cows were found to be highly bactericidal against H. pylori. Post-colostral milk did not show any bactericidal effect against H. pylori.

Lilius, EM, Marnila, P. The role of colostral antibodies in prevention of microbial infections. Current Opinion in Infectious Diseases 14(3): 295-300 (2001). Colostrum offers passive protection against a variety of microbial pathogens in the form of specific immunoglobulin A, G and M antibodies. It is especially effective in the prevention of various gastroenteric infections.

Lilius EM, Marnila P. Curr Opin Infect Dis. 2001 Jun;14(3):295-300. Related Articles, Links, The role of colostral antibodies in prevention of microbial infections. Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland.

Masson, PL, et al. An iron-binding protein common to many external secretions. Clinica Chemica Acta 14:735 (1966). Lactoferrin inhibits the growth of siderophilic (iron-loving) bacteria and Candida albicans.

Majumdar, A. S., et al., Protective properties of anti-cholera antibodies in human colostrum. Infect. Immun. 1982. 36:p. 962965.

McClead, R., et al., Resistance of bovine anti-cholera toxin IgG to in vitro and in vivo proteolysis. Pedia. Res. 1982.6: p. 227-231.

McClead RE Jr, Butler T, Rabbani GH. Am J Med. 1988 Dec;85(6):811-6. Related Articles, Links, Orally administered bovine colostral anti-cholera toxin antibodies: results of two clinical trials. Department of Pediatrics, Ohio State University 43205.

Morris, J. A., et al., Passive protection of lambs against enteropathogenic Escherichia coli: Role of antibodies in serum and colostrum. T. Med. Microbiol.1980. 13: p. 265-271.

McClead RE, Gregory SA. Infect Immun. 1984 May;44(2):474-8. Related Articles, Links, Resistance of bovine colostral anti-cholera toxin antibody to in vitro and in vivo proteolysis.

Michalek SM, McGhee JR. (1977) Effective immunity to dental caries: passive transfer to rats to antibodies to streptococcus mutans elicits protection. Infection and Immunity. 17:644-650.

Opdebeeck JP, Norcross NL. Am J Vet Res. 1985 Jul;46(7):1561-4. Related Articles, Links, Antibodies in bovine serum and lacteal secretions to capsular antigens of Staphylococcus aureus.

Ogra, PL, et al. Colostrum derived immunity and maternal neonatal interaction. Annals of the New York Academy of Sciences 409: 82-92 (1983). Peyer's patches are found throughout the intestinal tract, and groups of similar immunoactive cells are found in the bronchial mucosa. Both the intestinal and bronchial immunoactive cell groups respond to allergens, antigens and pathogens by neutralizing or destroying them. In newborns, these special cell groups are not immediately operative but protection is provided by a variety of immune factors from the mother's colostrum. Antibodies found in colostrum protect against Eschericia coli, Salmonella, Shigella, Vibrio cholera, Bacteriodes fragilis, Streptococcus pneumoniae, Bordtella pertussis, Clostridium diphtheria, Clostridium tetani, Streptococcus mutans and Candida albicans.

Paulsson, MA, et al. Thermal behavior of bovine lactoferrin in water and its relation to bacterial interaction and antibacterial activity. Journal of Dairy Science 76(12):3711-3720 (1993). Lactoferrin which was either unheated or pasteurized showed similar activity, while lactoferrin exposed to UHT treatment decreased its ability to bind to bacterial species and destroyed its ability to inhibit bacterial growth.

Spik, G., et al., Bacteriostasis of a milk-sensitive strain of E. coli immunoglobulins and iron-binding proteins associated with colostrum. Immunology 1981. 35: p. 663-670.

Seifert J, Molkewehrum M, Oesser S, Nebermann L, Schulze C. Eur Surg Res. 2002 Jan-Apr;34(1-2):68-72. Related Articles, Links, Endotoxin inactivation by enterally applied colostrum of different composition. Surgical Research, Department of Surgery and Thoracic Surgery, Kiel, Germany.

Stephan W, Dichtelmuller H, Lissner R. J Clin Chem Clin Biochem. 1990 Jan;28(1):19-23. Related Articles, Links, Antibodies from colostrum in oral immunotherapy. Biotest Pharma GmbH, Forschungsabteilung, Frankfurt.

Tacket CO, Binion SB, Bostwick E, Losonsky G, Roy MJ, Edelman R. Am J Trop Med Hyg. 1992 Sep;47(3):276-83. Related Articles, Links, Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Department of Medicine, University of Maryland School of Medicine, Baltimore.

Tacket CO, Losonsky G, Link H, Hoang Y, Guesry P, Hilpert H, Levine MM. N Engl J Med. 1988 May 12;318(19):1240-3. Related Articles, Links, Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. Department of Medicine, University of Maryland School of Medicine, Baltimore.

Takakura N. et al."Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model."J Med Microbiol. 2004 Jun;53(Pt 6):495-500.

Ushijima H, Dairaku M, Mukoyama A. Kansenshogaku Zasshi. 1991 Jan;65(1):54-60. Related Articles, Links,[Bacteriostatic activity of bovine colostrum][Article in Japanese],Department of Enteroviruses, National Institute of Health.

Wada, T, et al. The therapeutic effect of bovine lactoferrin in the host infected with Helicobacter pylori. Scandinavian Journal of Gastroenterology 34(3):238-243 (1999). Mice infected with H. pylori were given a daily dose of bovine lactoferrin for 2-4 weeks. Their intestines were then examined for bacterial content. Numbers of H. pylori were reduced to 10% of pre-lactoferrin levels and greatly decreased the numbers of H. pylori bound to the intestinal wall. Serum antibody titer to H. pylori were reduced to practically zero, indicating that the immune response of the host was no longer recognizing H. pylori infection. Therefore it was deduced that lactoferrin has a direct antibacterial effect on H. pylori infection and prevents binding of the pathogen to the intestinal lining.

Wada, N., et al., Neutralizing activity against Clostridium difficile toxins in the supernatants of cultured colostral cells. Infect. Immun.. 1980.29: p. 545-550.

Watzl, B., et al., Enhancement of resistance to Cryptosporidium parvum by pooled bovine colostrum during murine retroviral infection. Am. T. Trop. Med. Hyg. 1993. 48(4): p. 519-523.

For Additional Links: www.scholar.google.com keywords: Colostrum, Anti-bacterial

Cancer

Gross, Neil; Carey, John; Hamilton, Joan. "Quiet Strides in the War on Cancer" Business Week. February 6:150, 1995.

Lidbeck, A.; Allinger, U. G.; Orrhage, K. M.; Ottova, L.; Brismar, B.; Gustafsson, J. A.; Rafter, J.; Nord, C. E. "Impact of Lactobacillus Acidophilus Supplements on the Fecal Microflora and Soluble Fecal Bile Acids in Colon Cancer Patients," Microbial Ecology in Health and Disease. 4:81-8, 1991.

Lidbeck, A.; Nord, C. E.; Gustafsson, J. A.; Rafter, J. "Lactobacilli, Anticarcinogenic Activities and Human Intestinal Microflora," Eur J Cancer Prev. 1:341-353, 1992.

Shahani, K. et al, Antitumor activity of fermented colostrum and milk 01-May-83 - Investigated the effect of feeding fresh colostrum and colostrum cultured with either L. acidophilus, L. bulgaricus or yoghurt starter on the proliferation of ascites tumor cells.

Parodi, PW. Cows' milk fat components as potential anticarcinogenic agents. Journal of Nutrition 127(6):1055-1060 (1997). Including dairy products in the diet has been shown to lessen the chance of developing cancer. One of the ways dairy products accomplish this is through the anticarcinogenic properties of several milk fats, including conjugated linoleic acid (CLA), sphingomyelin, butyric acid and ether lipids. Cows also have the ability to absorb anticarcinogenic compounds, such as beta-carotene, beta-ionone and gossypol, from their feed and include them in their milk.

Parodi, PW. Conjugated linoleic acid and other anticarcinogenic agents of bovine milk fat. J Dairy Sci. 1999 Jun;82(6):1339-49.. CLA in even small amounts has a potent anticarcinogenic effect, as does sphingomyelin. Other components of milk with anticarcinogenic activity include butyric acid, ether lipids, beta-carotene and vitamins A and D.

Pizza, G, et al. A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer. Biotherapy 9(1-3):123-132 (1996). Transfer factor (PRPs) increased the survival rate of stage D3 prostate cancer patients.

See, D, et al. Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers. Immunological Investigations 31(2):137-153 (2002). PRPs are known to increase the production of both TNF-alpha and NK cell activity. This treatment strategy has shown promise in the treatment of terminal cancers.

For Additional Links: www.scholar.google.com keywords: Colostrum, Cancer

Cytokines

Blach-Olszewska, Z, Janusz, M. Stimulatory effect of ovine colostrinine (a proline-rich polypeptide) on interferons and tumor necrosis factor product by murine resident peritoneal cells. Archivum Immunologiae et Therapie Experimentalis (Warsaw) 45(1):43-47 (1997). Colostrinin stimulates the production of tumor necrosis factor-alpha (TNF-a) and interferon-beta (INF-ß), both important cytokines in the inflammatory response.

Bocci, V, et al. What is the role of cytokines in human colostrum? Journal of Biologic Regulatory and Homeostatic Agents 5(4):121-124 (1991). The cytokines present in colostrum, such as TNF-a, interferon-g, IL-1 and IL-6, have an immunostimulatory effect. This could be significant for aged people or others with immunodeficiency.

Bessler, H., et al. Human colostrum stimulates cytokine production. Biology of the Neonate 69(6):376-382 (1996). Colostrum has also been shown to stimulate the production of certain cytokines, IL-1, IL-3 and IL-6, in peripheral white blood cells (monocytes).

Bogdan, C, Nathan, C. Modulation of macrophage function by transforming growth factor beta, interleukin-4, and interleukin-10. Annals of the New York Academy of Science 685:713-739 (1993). Certain cytokines found in colostrum, TGF-ß, IL-4 and IL-10, have a modulatory effect on macrophages, either stimulating or deactivating them as conditions dictate.

Feldmann, M, et al. Cytokines in autoimmune disorders. International Review of Immunology 17(1-4)217-228 (1998). Cytokines are important protein mediators of immunity, inflammation, cell proliferation, differentiation, fibrosis, and so forth, in other words, all the major biological processes which underlie autoimmune disorders. Modulating the effects of these cytokines, particularly TNF-a, can result in amelioration of the symptoms of the disorders.

Hagiwara, K, et al. Detection of cytokines in bovine colostrum. Veterinary Immunology and Immunopathology 76:183-190 (2000).

Inglot, A.D., et al. "Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes." Arch Immunol Ther Exp (Wasz), 1996;44(4):215-224.

Zoltan P. Rona, M.D., M.Sc., Bovine Colostrum Emerges as Immunity Modulator, American Journal of Natural Medicine, March 1998.

For Additional Links: www.scholar.google.com keywords: Colostrum, Cytokines

Diabetes (also see IgF studies in 'Growth Factors')

"A New Way to Fight Diabetes" Newsweek. November 15, 1993. Dohm, G. L.; Elton, C. W.; Raju, M. S.; Mooney, N. D.; DiMarchi, R.; Pories, W. J.; Flickinger,

Aranda P. "Insulin in bovine colostrum and milk: evolution throughout lactation and binding to caseins." J Dairy Sci. 1991 Dec;74(12):4320-5..

Binz, K. et al. Repopulation of The Atrophied Thymus in Diabetic Rats by Insulin-like Grown Factor I. Proc. Natl. Acad. Sci. USA. 87(10):3690-3694. May 1990.

Chen, W, et al. Insulin-like growth factor (IGF)-I/IGF-binding protein-3 complex: therapeutic efficacy and mechanism of protection against type 1 diabetes. Endocrinology 145(2):627-638 (2004). IGF-1 regulates beta cell growth, survival and metabolism in the pancreas and protects them against development of type 1 diabetes. Using IGF-1 combined with IGF-binding protein (IGF-bp) significantly increases the efficacy of IGF-1 treatment by extending its half-life in the body.

Dohm, Elton, et al. IgF-1 stimulated glucose transport. Diabetes, Sept. 30, 1990, pp. 1028-32.

Dohm. G.; et al. "IGF-1 Stimulated Glucose Transport in Human Skeletal Muscle and IGF-I Resistance in Obesity and NIDDM," Diabetes. 39(9):1028-1032, 1990.

McDevitt, H. "Characteristics of Autoimmunity in Type 1 Diabetes and Type 1.5 Overlap With Type 2 Diabetes" Section I: Aspects of PathophysiologyDiabetes 54:S4-S10, 2005. Department of Medicine, and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California.

Pennisi. "Immune Therapy Stems Diabetes Progress" Science News. 145:37, January 15, 1995.

Tuomi, T. "Type 1 and Type 2 Diabetes, What Do They Have in Common?" Section I: Aspects of Pathophysiology Diabetes 54:S40-S45, 2005. From the Department of Internal Medicine/Diabetology, Helsinki University Central Hospital; the Institute for Diabetes Genetics, Folkhalsan Research Center, Helsinki, Finland; and the Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland.

Stone, T. "Components in Colostrum Balance Blood Sugar Levels and Reduce Insulin Requirements" Colostrum Can Stabilize Blood Sugar, 1993

Thivolet, C. Use of IGF-1 or analogues thereof in the prevention of diabetes. US Patent #6,342,227 (2002). IGF-1 or an analogue can delay the clinical onset of diabetes when administered at the first sign of the disease. Additionally, IGF-1 or analogue given to patients at high risk for developing the disease significantly reduces the likelihood of developing diabetes.

Vaarla, O. The gut immune system and type 1 diabetes. Annals of the New York Academy of Science 958:39-46 (2002). There is increasing evidence that the gut immune system is important in the development of type 1 (autoimmune) diabetes. One of the causes of type diabetes in children may be too early introduction of cow’s milk to the diet in infants, which causes an autoimmune response to insulin.

For Additional Links: www.scholar.google.com keywords: Colostrum, Diabetes

General Information

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