Colostrum Research ~
COLOSTRUM & COLOSTRUM, DERIVATIVE RESEARCH The newborn for whom the colostrum is intended is a blank tablet, immunologically speaking. It needs protection from the environment it has just entered, and it needs it immediately if it is to survive. Therefore colostrum, whether it is from a cow or a human, is loaded with everything the newborn needs to survive in the hostile world. Cows, unlike humans, are unable to receive immunoglobulins across the placenta to “prime” the immune system before birth, so they need a massive dose of immunoglobulins immediate after birth.
Bovine colostrum thus contains much more Immunoglobulin G (IgG) than human colostrum, which contains predominantly Immunoglobulin A (IgA). IgG provides passive systemic immunity whereas IgA provides more localized immunity. Bovine colostrum is able to impart passive immunity not only to calves but to humans as well against a broad spectrum of pathogens as well as nonspecific immune support against all pathogens, including bacteria, viruses, fungi and protozoan parasites.
Colostrum also has the unique ability to modulate the immune system through the activity of colostrinin, a protein found only in colostrum, which can heat up or cool down the immune system depending upon what is needed by the host.
• Colostrum provides passive immunity against bacteria, viruses, fungi and protozoan parasites34-48 • Lactoferrin, lactoperoxidase and lysozyme are non-specific bactericidal, virucidal and fungicidal components of colostrum49-54 • Lactoferrin and lysozyme have been shown to act in concert with lactoferrin first binding to and removing the lipopolysaccharide protective coating of gram-negative bacteria (such as Vibrio cholerae (cholera), Salmonella typhimurium (food poisoning) and Eschericia coli), allowing lysozyme to enter the bacterial cell, causing lysis55 • Lactoferrin is effective against HIV and Human Cytomegalovirus56,57 • Colostrum alleviates Cryptosporidosis, a life-threatening diarrhea which occurs as a secondary infection in AIDS58-60 • Colostrum contains complement factors and oligosaccharides which also provide non-specific antimicrobial protection61,62 • Colostrum contains colostrinin® (or PRP), a unique immunomodulatory peptide which causes the differentiation of thymocytes into active T cells and stimulates the differentiation of B cells and can also act to tone down on overactive immune system, such as is found in autoimmune diseases63,64 • colostrinin® also stimulates the production of interferon-beta (IFN β) and tumor necrosis factor-alpha (TNF-α) by peritoneal cells65 • Oral administration of interleukin-1beta (IL-1β) from colostrum causes a marked increase in the proliferation of peripheral blood mononuclear cells, indicating that colostrum stimulates the immune system66 • Cytokines, such as tumor necrosis factor- alpha (TNF-α), interleukins (IL-1α, IL-1β, IL-6) and interferon (IFNγ) in colostrum, stimulate the developing immune system in infants as well as the depressed immune system of aged individuals67 • Colostrum stimulates the formation of cytokines, interleukins 1, 3 and 6 (IL-1, IL-3, IL-6), by blood leukocytes68 • Transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), both found in colostrum, modulate the activity of monocytes and macrophages in organizing immune responses to pathogens, either turning them on or off depending on what is needed69 • Lactoferrin from colostrum increase both motility and superoxide production by polymorphonuclear leukocytes (white blood cells), apparently making them more effective in warding off infections70 • Colostrum can modulate natural killer cell activity by stimulating or inhibiting production of interleukin-2 (IL-2)71
Research References 1. Lock, TJ. Review paper: Processing and its effect on colostrum powder quality. Oak on Elm, Ltd. (1999) 2. Efigenia, M, et al. Effect of heat treatment on the nutritional quality of milk proteins. International Dairy Journal 7:609-612 (1997). The effect of heating and pasteurization on the nutritional quality of milk proteins was examined. Pasteurization, while destroying harmful pathogens, does not affect the biological value of milk proteins. Boiling, on the other hand, affects liver protein synthesis from ingested milk protein. 3. Li-Chan, E, et al. Stability of bovine immunoglobulins to thermal treatment and processing. Food Research International 28(1):9-16 (1995). Milk exposed to commercial pasteurization processes retained high levels of IgG activity, whereas canned evaporated milk or sterilized milk had little or no IgG activity. 4. Bangham, AD, et al. Diffusion of univalent ions across the lamellae of swollen phospholipids. Journal of Molecular Biology 13(1):238-252 (1965) 5. Lasic, DD, et al. Spontaneous vesiculation. Advances in Colloid and Interface Science 89-90:337-349 (2001). The thermodynamics of vesicle formation was analyzed by using the elastic bending energy approach. Several different possibilities of spontaneous vesiculation, due to soft bilayers, non-zero spontaneous curvature and Gaussian curvature, respectively, were presented and discussed. Intermediate structures in the closed vesicle-disklike mixed micelle phase transition could be either cup-like particles or open bilayers partially rolled into lipid tubules. 6. Wong, A, Toth, I. Lipid, sugar and liposaccharide based delivery systems. Current Medicinal Chemistry 8(9):1123-1136 (2001). Liposomes can be altered chemically by adding sugars and liposaccharides to get optimal absorption through a wide variety of membranes. 7. Haque, ME, et al. Influence of lipid composition on physical properties and peg-mediated fusion of curved and uncurved model membrane vesicles: “nature’s own” fusogenic lipid bilayer. Biochemistry 40(14):4340-4348 (2001). Sphingomyelin and cholesterol both must be present in order to produce an exact replica of cell membranes. 8. Igarashi, A., et al. Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer. Toxicology Letters 145(2):133-141 (2003). Photodynamic therapy using light-sensitive chemicals such as photofrin and delivered via liposomes offers a potent and less invasive treatment for stomach and intestinal cancers. Use of liposomes as a delivery vehicle significantly increased accumulation of photofrin in tumors with a subsequent increase in therapeutic effect. 9. Rivera, E. Liposomal anthracyclines in metastatic breast cancer: clinical update. Oncologist 8(Suppl.2):3-9 (2003). Delivering anthracyclines – a common treatment for metastatic cancer – using liposomes avoids many of the severe side effects normally associated with its use while increasing the therapeutic index of its efficacy. 10. Justo, OR, Moraes, AM. Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation. Drug Delivery 10(3):201-207 (2003). Encapsulating antibiotics used in tuberculosis therapy inside liposomes allows for their delivery by inhalation, which increases their efficacy. 11. Steele, G, Jr, et al. Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes. Surgery 96(2):352-359 (1984). Tissue type-specific immunogens (cancer proteins) are used to protect against the recurrence of tumors, but are only effective if histocompatible. Placing the immunogens in liposomes, however, increases the survival of test animals regardless of histocompatibility. 12. Lopez-Berestein, G, et al. Prophylaxis of Candida albicans infection in neutropenic mice with liposome-encapsulated amphotericin B. Antimicrobial Agents and Chemotherapy 25(3):366-367 (1984). Amphotericin B protected by liposome encapsulation was effective against Candida infection whereas unprotected Amphotericin B was not. 13. Chaize, B, et al. Encapsulation of enzymes in liposomes: high encapsulation efficiency and control of substrate permeability. Artificial Cells, Blood Substitutes, and Immobilization Technology 32(1):67-75 (2004). Encapsulation in liposomes prevents denaturization of acetylcholinesterase enzyme in the gastrointestinal tract. 14. Sato, H, et al. Enhancement of the intestinal absorption of a cyclosporine derivative by milk fat globule membrane. Biological and Pharmaceutical Bulletin 17(11):1526-1528 (1994). Adding milk fat globule phospholipids to cyclosporine significantly increased absorption through the intestine in rats. 15. Yuasa, H, et al. Evaluation of milk fat-globule membrane (MFGM) emulsion for oral administration: absorption of alpha-linolenic acid in rats and the effect of emulsion droplet size. Biological and Pharmaceutical Bulletin 17(5):756-758 (1994). Using alpha-linoleic acid as a test substance, absorption of was increased using liposomes made from milk fat globule membranes. 16. Imokawa, G, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? Journal of Investigative Dermatology 96(4):523-526 (1991) Decreased levels of ceramides – a metabolite of sphingomyelin – is associated with dry skin, indicating that ceramides are vital for maintaining the water retention function of the skin. 17. Man, MQM, et al. Optimization of physiological lipid mixtures for barrier repair. Journal of Investigative Dermatology 106(5):1096-1101 (1996). Certain lipids in the skin, ceramides, cholesterol and free fatty acids, must be present in the proper proportions to maintain barrier function in the skin. Adding these lipids to damaged skin could help with healing the damage. 18. Madison, KC. Barrier function of the skin: “la raison d’etre” of the epidermis. Journal of Investigative Dermatology 121(2):231-241 (2003). Keeping the outside out and the inside in is the primary function of the skin. Lipids in the skin are the primary component of this barrier. Repair of the barrier function is necessary to heal damaged skin or diseased skin. 19. Bibel, DJ, et al. Sphingosines: antimicrobial barriers of the skin. Acta Dermato-Venereologica 73(6):407-411 (1993). Sphingosines, another metabolite of sphingomyelin, play an important role in the bacteriostatic and fungistatic function of the skin. 20. Nunzi, MG, et al. Therapeutic Properties of Phosphatidylserine in the Aging Brain. Phospholipids New York, Plenum, pp.213-218 (1990). The lipid content of the brain changes with age, leading to loss of membrane fluidity, enzymatic activities, and membrane receptors, and a decreased efficiency of signal mechanisms. This is accompanied by a deterioration in brain function. Supplementation with phosphatidylserine has been shown to counteract these changes to a degree. 21. Amaducci, L, et al. Use of phosphatidylserine in Alzheimer’s disease. Annals of the New York Academy of Science 640:245-249 (1991). Phosphatidylserine has shown promise in helping to counteract the effects of Alzheimer’s disease on brain function. 22. Fünfgeld, EW, Nedwidek, P. Neurohomologous phosphatidylserine in Parkinsonian patients with associated disorders of cerebral metabolism. Clinical Trials Journal 24(1):42-61 (1997). Giving phosphatidylserine to patients demonstrating symptoms of organic brain syndrome in association with Parkinson’s disease showed up to 10% lessening of symptoms in some patients. 23. Murphy, EJ, et al. Phospholipid composition and levels are altered in Down syndrome brain. Brain Research 867(1-2):9-18 (2000). Changes in the phospholipid content of brains from patients with Down syndrome (mongoloidism) most likely are due to the effects of the disease. Similar changes have been observed in other neurological disorders. 24. Monteleone, P, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 52(3):243-248 (1990). Administering phosphatidylserine to subjects and then subjecting them to stress blunted the increase in ACTH and cortisol levels normally seen. 25. Monteleone, P, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. European Journal of Clinical Pharmacology 42(4):385-388 (1992). A follow-up to the previous study which indicated that long-term use of phosphatidylserine supplement can counter the effects of stress. 26. Benton, D, et al. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutritional Neuroscience 4(3):169-178 (2001). This study showed that phosphatidylserine supplementation can also improve the mood of subjects under stress. Obeid, LM, et al. Programmed cell death induced by ceramide. Science 259(5102):1769-1771 (1993). Sphingomyelin has been shown to be an important link in the signaling mechanism for controlling programmed cell death (apoptosis), cell growth and differentiation. The hydrolysis of sphingomyelin into ceramide acts to turn on tumor necrosis factor-alpha (TNF- α ) and other cytokines, which in turn produces apoptosis. This has been used successfully in the treatment of leukemia. 27. Parodi, PW. Cows’ milk fat components as potential anticarcinogenic agents. Journal of Nutrition (127(6):1055-1060 (1997). Some of the milk fats found normally in milk and colostrum have been show to have anticarcinogenic effects, including sphingomyelin and conjugated linoleic acid (CLA). 28. Dial, EJ, Lichtenburger, LM. A role for milk phospholipids in protection against gastric acid. Studies in adult and suckling rats. Gastroenterology 87(2):379-385 (1984). Phospholipids found in raw milk protect the stomach from excess gastric acid, thus providing protection from ulcers. 29. Palmer, EL, et al. Antiviral activity of colostrum and serum Immunoglobulins A and G. Journal of Medical Virology 5:123-129 (1980). Virus-specific IgA was discovered in colostrum, including anti-polio antibody. 30. Ogra, PL, et al. Colostrum-derived immunity and maternal-neonatal interaction. Annals of the New York Academy of Sciences 409:82-95 (1983). Passive immunity to specific pathogens is passed from mother to infant via colostrum. 31. Brüssow, H., et al. Bovine milk immunoglobulins for passive immunity to infantile rotavirus gastroenteritis. Journal of Clinical Microbiology 25(6):982-986 (1987). Protection against rotavirus, a dangerous pathogen which can cause serious, even fatal diarrhea in infants, can be passed orally through milk or colostrum safely and effectively. 32. Ebina, T, et al. Passive immunizations of suckling mice and infants with bovine colostrum containing antibodies to human rotavirus. Journal of Medical Virology 38:117-123 (1992). Another study that confirmed that oral immunization via colostrum or milk against rotavirus was possible, safe and effective. 33. Stephan, W, et al. Antibodies from colostrum in oral immunotherapy. Journal of Clinical Chemistry and Clinical Biochemistry 28:19-23 (1990). An immunoglobulin preparation from pooled bovine colostrum was found to be very effective in treating severe diarrhea, such as often found in AIDS patients. 34. van Hooijdonk, AC, Kussendrager, KD, Steijns, JM. In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defense. British Journal of Nutrition 84(Suppl.1):S127-S134 (2000). Lactoferrin and lactoperoxidase, both present in colostrum in large amounts, provide non-specific defense against a broad spectrum of pathogens, including bacteria and viruses. This is significant both for the protection of commercially important animals as well as humans. 35. Korhonen, H, et al. Bovine milk antibodies for health. British Journal of Nutrition 84(Suppl.1):S135-S146 (2000). Bovine colostrum provides safe, effective protection against many pathogens. This natural immune protection can be extended by hyperimmunizing cows against specific pathogens. 36. Solomons, NW. Modulation of the immune system and the response against pathogens with bovine colostrum concentrates. European Journal of Clinical Nutrition 56(Suppl.3):524-528 37. Kivinen, A, et al. Gastroprotective effect of milk phospholipids, butter serum lipids and butter serum on ethanol and acetylsalicylic acid induced ulcers in rats. Milchwissenschaft 1991:573-575 (1991). Another study that demonstrated the ability of milk phospholipids to protect the stomach from ulcers produced by stomach acid. 38. Lichtenburger, LM, et al. Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: combination therapy with anti-secretory agents in rats. Gastroenterology 111(4):990-996 (1996). Combining phospholipid supplements with NSAID drugs reduces damage to the gastrointestinal lining and increases the therapeutic effect of the drugs. 39. Anand, BS, et al. Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects. American Journal of Gastroenterology 94(7):1818-1822 (1999). Similar results were found when phospholipids were combined with aspirin. 40. Carlson, SE, et al. Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids. Pediatric Research 44(4):491-498 (1998). Necrotizing enterocolitis, a severe inflammation of the gut in newborn infants which causes some 4,000 deaths annually in the US, has a lower incidence when newborns are given formula containing phospholipids. 41. Sabin, AB. Anti-poliomyelitic substance in milk from human beings and certain cows. Journal of Diseases of Children 80:866-870 (1950). Seminal study by Dr. Albert Sabin, inventor of the oral polio vaccine, in which he discovered antibodies against the polio virus in colostrum. 42. Solomons, NW. Modulation of the immune system and the response against pathogens with bovine colostrum concentrates. European Journal of Clinical Nutrition 56(Suppl.3):524-528 (2002). The ability of colostrum to protect infants against pathogens, specifically those which cause gastroenteritis and severe diarrhea, makes it an ideal, cheap, safe and effective means of protecting children in those parts of the world where medical assistance is lacking or substandard and could save thousands of lives each year. 43. Ho, PC, Lawton, JWM. Human colostral cells: Phagocytosis and killing of E. Coli and C. Albicans. Journal of Pediatrics 93(6):910 –915 (1978). Cells found in colostrum are able to ingest and kill both E. coli and Candida. 44. Majumdar, AS, et al. Protective properties of anti-cholera antibodies in human colostrum. Infection and Immunity 36:962-965 (1982). Colostrum was able to prevent infection with cholera. Colostrum samples from India, where cholera is common, had much higher levels of anti-cholera IgA than those from Sweden, where cholera is rare. 45. Funatogawa, K, et al. Use of immunoglobulin enriched bovine colostrum against oral challenge with enterohaemorrhagic Eschericia coli O157:H7 in mice. Microbiology and Immunology 46(11):761-766 (2002). Colostrum can prevent infection against food-borne pathogens by preventing them from binding to the intestinal lining. 46. Widiasih, DA, et al. Passive transfer of antibodies to Shiga toxin-producing Eschericia coli O26, O111 and O157 antigens in neonatal calves by feeding colostrum. Journal of Veterinary Medicine 66(2):213-215 (2004). Feeding colostrum to calves provided protection against Shiga toxin-producing E. Coli, a particularly deadly strain of E. coli. 47. Acosta-Altamirano, G, et al. Anti-amoebic properties of human colostrum. Advances in Experimental Medicine and Biology 216B:1347-1352 (1987). In addition to its effectiveness against bacterial, viral and fungal infections, colostrum also provides protection against amoebic pathogens. 48. Akisu, C, et al. Effect of human milk and colostrum on Entamoeba histolyica. World Journal of Gastroenterology 10(5):741-742 (2004). Colostrum was found to provide protection against Entamoeba histolyica, the cause of amoebiasis, a serious, chronic illness characterized by dysentery, gastrointestinal ulceration and abscess formation and intestinal blockage in infants particularly. 49. Edde, L, et al. Lactoferrin protects neonatal rats from gut-related systemic infection. American Journal of Physiology: Gastrointestinal Liver Physiology 281:G1140-G1150 (2001). Lactoferrin protected neonatal rats from E. coli infection in the intestines. Lactoferrin plus lysozyme was bactericidal against the E. coli. 50. Qiu, J, et al. Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae. Proceedings of the National Academy of Sciences USA 95:12641-12646 (1998). Lactoferrin prevents colonization of Haemophilus influenzae, the primary cause of otitis media and other respiratory infections in children, by inactivating two colonization factors expressed by the bacteria. 51. Hasegawa, K, et al. Inhibition with lactoferrin of in vitro infection with human herpes virus. Japanese Journal of Medical Science and Biology 47:73-85 (1994). Both human and bovine lactoferrin inhibit infection with human herpes simplex virus and human cytomegalovirus in cell cultures. 52. van der Strate, BW, et al. Antiviral activities of lactoferrin. Antiviral Research 52(3):225-239 (2001). Lactoferrin is effective against both DNA and RNA viruses, including rotavirus, respiratory syncytial virus, herpes virus and HIV, both by blocking cellular receptors and by directly binding to the viruses. 53. Andersson, Y, et al. Lactoferrin is responsible for the fungistatic effect of human milk. Early Human Development 59:95-105 (2000). Lactoferrin, through its iron-binding ability, is very effective against fungal infections with Candida and other fungi. 54. Samaranayake, YH, et al. Antifungal effects of lysozyme and lactoferrin against genetically similar, sequential Candida albicans isolates from a human immunodeficiency virus-infected Southern Chinese cohort. Journal of Clinical Microbiology 39(9):3296-3302 (2001). Lactoferrin plus lysozyme is very effective in killing nearly all oral strains of Candida, which is of particular importance to AIDS sufferers who are often unable to fight off Candida overgrowths, such as thrush. 55. 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. 56. Harmsen, MC, et al. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. Journal of Infectious Diseases172(2):380-388 (1995). Lactoferrin can protect against infection by HIV and human cytomegalovirus by blocking entrance into the body. 57. Berkhout, B, et al. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Research 55(2):341-355 (2002). Bovine lactoferrin as well as peptides derived from lactoferrin blocks the entry process of HIV into cells. 58. Rump, JA, et al. Treatment of diarrhea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Clinical Investigator 70:588-594 (1992). Immunoglobulins from bovine colostrum were very effective in treating chronic diarrhea in AIDS patients from a variety of causes. Colostral immunoglobulins are highly resistant to digestion in the gastrointestinal tract. 59. Plettenberg, A, et al. A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. Clinical Investigator 71(1):42-45 (1993). Another study which examined the use of immunoglobulins from bovine colostrum in the treatment of chronic diarrhea in AIDS patients. 40% of the study group experienced complete remission of symptoms and 24% partial remission. 60. Greenberg, PD, Cello, JP. Treatment of severe diarrhea caused by Cryptosporidium parvum with oral bovine immunoglobulin concentrate in patients with AIDS. Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology 13(4):348-354 (1996). Another study which looked at the treatment of cryptosporidiosis diarrhea in AIDS patients with an immunoglobulin concentrate from bovine colostrum. Best results were found using a powdered form of the concentrate rather than in capsules. 61. 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. 62. 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. 63. Janusz, M, Lisowski, J. Proline-rich polypeptide (PRP) – an immunomodulatory peptide from ovine colostrum. Archivum Immunologiae et Therapiae Experimentalis 41:275-279 (1993). A unique, non-species specific polypeptide which plays an immunomodulatory role in the immune system. It can induce the differentiation of thymocytes into functional T-cells as well as increase the permeability of skin blood vessels. What makes it unique is that a second exposure to the polypeptide reverses the changes induced by first exposure. 64. Julius, MH, et al. A colostral protein that induces the growth and differentiation of resting B lymphocytes. Journal of Immunology 140:1366-1371 (1988). Colostrinin has also been shown to induce the growth and differentiation of resting B lymphocytes. T and B lymphocytes are the two main types of lymphocytes involved in the immune response. 65. 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-α) and interferon-beta (INF-β), both important cytokines in the inflammatory response. 66. Hagiwara, K, et al. Oral administration of IL-1 beta enhanced the proliferation of lymphocytes and the O(2)(-) production of neutrophil in newborn calf. Veterinary Immunology and Immunopathology 81(1-2):59-69 (2001) Interleukin-1β in colostrum stimulates the immune system by increasing the amount of peripheral white blood cells, especially monocytes. 67. 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-α, interferon-γ, IL-1 and IL-6, have an immunostimulatory effect. This could be significant for aged people or others with immunodeficiency. 68. 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). 69. 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-β, IL-4 and IL-10, have a modulatory effect on macrophages, either stimulating or deactivating them as conditions dictate. 70. Gahr, M, et al. Influence of lactoferrin on the function of human polymorphonuclear leukocytes and monocytes. Journal of Leukocyte Biology 49(5):427-433 (1991). White blood cells (polymorphonuclear leucocytes) exposed to lactoferrin from bovine colostrum exhibit increased motility and produce more superoxide (a powerful antioxidant). 71. Sirota, L, et al. Effect of human colostrum on interleukin-2 production and natural killer cell activity. Archive of Diseases in Childhood: Fetal and Neonatal Edition 72(3):F99-102 (1995). Colostrum stimulates or inhibits the production of IL-2 depending on its concentration. It also inhibits the activity of natural killer cells, but the production of IL-2 reverses this effect. This is thought to be another way that colostrum modulates the immune system response. 72. 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. 73. Prosser, C, et al. Reduction in heat induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. Journal of Applied Physiology 96:650-654 (2004). Bovine colostrum healed “leaky gut” in an experimental rat model used heat induced gastrointestinal hyperpermeability. 74. Gastrointestinal Inflammation and Repair Group, Imperial College, London (2003). Unpublished research. In an in vitro experimental study, colostrum stimulated intestinal cell growth and reestablished a healthy epithelial layer following injury. In an in vivo experimental study, colostrum powder was also shown to reduce gastric injury. 75. Bitzan, MM, et al. Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid receptors by bovine colostrum. Journal of Infectious Diseases 177:955-961 (1998). Bovine colostrum blocked binding of H. pylori (a major cause of chronic gastritis and ulcers in humans) and H. mustelae (a similar pathogen found in ferrets). This is apparently a function of the phosphatidylethanolamine found in colostrum and BIO-lipid. 76. Korhonen, H. Bactericidal effect of bovine normal and immune serum, colostrum and milk against Helicobacter pylori. Journal of Applied Bacteriology 78:655-662 (1995). The antibody-complement system found in bovine colostrum was also found to be bactericidal against H. pylori. 77. Carver, JD, Barness, LA. Trophic factors for the gastrointestinal tract. Clinical Perinatology 23(2):265-285 (1996). Factors in colostrum which promote the development of the GI tract in newborn infants also help protect against such diseases as Crohn’s disease, colitis, necrotizing enterocolitis and diarrhea. 78. Bühler, C., et al. Small intestinal morphology in eight-day-old calves fed colostrum for different durations or only milk replacer and treated with long-R3-insulin-like growth factor I and growth hormone. Journal of Animal Science 76:758-765 (1998). The intestines of calves fed colostrum compared to those not fed colostrum revealed that those fed colostrum had significantly increased villus size and crypt depths. This translates into greater surface area and thus increased absorption of nutrients. 79. Blättler, U, et al. Feeding colostrum, its composition and feeding duration variably modify proliferation and morphology of the intestine and digestive enzyme activities of neonatal calves. Journal of Nutrition 131(4):1256-1263 (2001). A similar study done on calves either receiving or not receiving colostrum. This study concentrated on the development and health of the gastrointestinal epithelium and found that the development and health of this epithelium was markedly superior in those receiving colostrum. Colostrum also influenced the production of lipase enzyme by the pancreas. 80. Pluske, JR, Morel, PCH. Increasing weaner pig productivity in New Zealand pig herds. Unpublished research (1999). Piglets fed a liquid supplement with colostrum powder had a marked increase in villi height in the lumen of the small intestine, indicating greater digestion and absorption of nutrients. There were also an increased number of immune cells in the villi, indicating enhanced immune competency. 81. 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. 82. 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. 83. 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. 84. 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. 85. 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-α receptor proteins, which are found in colostrum. These bind to TNF-α, which inactivates the TNF-α. TNF-α 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. 86. Feldmann, M, et al. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology 14:397-440 (1996). This study confirmed that TNF-α is the major controlling factor in the inflammatory response seen in rheumatoid arthritis. Therefore the ability of colostrum to modulate the activity of TNF-α may be the way in which colostrum is of benefit to those suffering from rheumatoid arthritis (and other types of arthritis as well). 87. Hagiwara, K, et al. Detection of cytokines in bovine colostrum. Veterinary Immunology and Immunopathology 76:183-190 (2000). Colostrum contains five cytokines, TNF-α, IL-1β, IL-6, IL-1ra (receptor antagonist) and INF-γ, which have known immunomodulatory effects. 88. 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-α, can result in amelioration of the symptoms of the disorders. 89. De Keyser, F, et al. Gut inflammation and spondyloarthropathies. Current Rheumatology Reports 4(6):525-532 (2002). Spondyloarthropathies (SpA) are a related group of arthritic conditions which include ankylosing spondylitis, reactive arthritis, psoriatic arthritis and arthritis associated with inflammatory bowel disease. SpA have been correlated with gut inflammation and are immunologically related Crohn’s disease. Colostrum’s ability to control gut inflammation and modulate the activity of TNF-α indicate that it may be of benefit in SpA treatment. 90. Nitsch, A, Nitsch, FP. Clinical use of bovine colostrum. Journal of Orthomolecular Medicine 13(2) (1998). A colostrum preparation was used clinically to treat rheumatoid arthritis and osteoarthritis with good results. 91. 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. 92. 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. 93. Stanton, G, et al. Use of colostrinin, constituent peptides thereof, and analogs thereof, as oxidative stress regulators. US Patent #6,500,798 (2002). Colostrinin acts as a general purpose oxidative stress regulator. It can be used to reduce the effects of oxidative stress (i.e. free radicals) either locally, such as on the skin, or as a supplement for the entire body. 94. 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. 95. 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. 96. Leszek, J, et al. 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 47:377-385 (1999). Colostrinin has psycho-immuno-enhancing activity. It was given to patients with Alzheimer’s disease and mild to moderate dementia and compared to placebo and selenium, another putative natural treatment for Alzheimer’s. Colostrinin demonstrated stabilization of symptoms in 13 of 15 patients as compared to none in the selenium group. 97. 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. 98. 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. 99. 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. 1Crook, 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. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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. 9. 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.