Naturally Immune For Life

1. Fat-soluble vitamins (A, D, E and K) are essential for the maintenance and promotion of good health. The fat-soluble vitamins are not reduced when colostrum is commercially processed.
2. Vitamins (A, B12 and E) Health, vitality and growth of the newborn Minerals Amino acids Essential oil
3. Proline-rich polypeptide (PRP) Regulates the thymus gland.
4. Immunoglobulins (A, D, E, G and M) IgG neutralizes toxins and microbes in the lymph and circulatory system IgM destroys bacteria IgE and IgD are highly antiviral.
5. Lactoferrin An antiviral, anti-inflammatory and antibacterial iron-binding protein with therapeutic effects in cancer, HIV, Cytomegalovirus , herpes, chronic fatigue syndrome, Candidiasis and other infections.
6. Cytokines Regulates the duration and intensity of the immune response, responsible for cell-to-cell communication boost T-cell activity and the production of immunoglobulins.
7. Lysozyme It aids hydrolysis and boosts the immune system and is capable of destroying bacteria and viruses on contact.
8. Enzymes Lactoperoxidase-thiocyanate, xanthine oxidase and peroxidase oxidize bacteria through their ability to release of hydrogen peroxide.
9. Leukocytes Stimulates interferon production.
10. Trypsin Protease inhibitors – prevent the destruction of immune and growth factors in colostrum.
11. Lymphokines Mediates the immune response.
12. Oligopolysaccharides and glycoconjugates Attract and bind to pathogens preventing them from attaching or entering the mucous membranes.
13. Orotic acid Prevents haemolytic anaemia.
14. Growth factors Epithelial growth factor (EGF) Help in enhancing cell and tissue growth by stimulating DNA formation. Insulin-like growth factor-I and II (IGF-I and IGF-II) Fibroblast growth factor (FgF) Platelet-derived growth factor (PDGF) Transforming growth factors A (TgA) and Transforming growth factor B (TgB) Growth hormone (GH)
15. Proline-rich polypeptide (PRP) present in colostrum functions as a regulatory substance of the thymus gland. Lymphocyte and T-cell overproduction, allergy and autoimmune disease symptoms, i.e. pain, inflammation and swelling are inhibited by PRP. Also, PRP has been reported to improve or eliminate symptoms of autoimmune diseases like rheumatoid arthritis, myasthenia gravis, multiple sclerosis, lupus and allergies.
16.  Colostrum may have a beneficial function in the prevention of cardiovascular diseases due to the presence of PRP, the same effect as is observed in allergies and autoimmune diseases. Also, the growth hormones (GH) and growth factors like insulin-like growth factor-1 (IGF-1) in colostrum can raise the blood levels of HDL (high-density lipoprotein)-cholesterol, while lowering LDL (low-density lipoprotein)-cholesterol. Growth factors and GH also play a significant role in repairing the damage to heart muscle and promote the growth of new blood vessels in collateral coronary circulation.
17. It has been demonstrated that colostrum is helpful in reversing infection-induced inflammation occurring in the digestive tract of HIV patients, possibly through improvement of mucosal integrity, tissue repair and direct antimicrobial actions.
18. Colostrum also has antiviral, antifungal and antibacterial properties which enable it to kill different pathogens like Escherichia coli, rotavirus and Cryptosporidium. BC with a high antibody titre.
19. κ-casein, a component of human and bovine milk. κ-Casein is a glycosylated protein that was found to bind directly to the viral antigens through the glycosylated residue. These residues are integral for antiviral activity.
20. It has been reported that colostrum is capable of killing opportunistic infections caused by Candida albicans, Helicobacter pylori, five types of Streptococci and Cryptosporidium.
21. Recently, Wong et al. demonstrated that oral administration (1.0 g/kg) of BC (bovine colostrum) to C57BL/6 mice increased natural killer (NK) cell cytotoxicity, improved the immune response to primary influenza A virus (H1N1) infection and lessened viral burden in the lungs compared to controls. It was hypothesized that the small intestinal epithelial cells may be stimulated by colostrum, and the interaction between colostrum and immunity may partly depend on the colostrum components with innate receptors present in the intestinal epithelium, including toll-like receptors, namely TLR-2 and TLR-4. Skimmed and concentrated bovine late colostrum (SCBLC), i.e. colostrum obtained on the 6th or 7th day after parturition and processed, was also found to be effective in reducing the symptom rate of influenza virus in mice. This action was demonstrated to be mediated through an SCBLC-mediated rise in NK cell activity in Peyer’s patches, splenocytes and the lungs.
22. Colostrum has been shown to be 3 times more effective than vaccines, colostrum fed cows produce higher titres of antibody’s than hyperimmunized cows.
23. Colostrum alleviates symptoms of influenza and prevented death and weight loss in animals given a lethal dose of the influenza virus.
24. Colostrum contains leptin that induces satiety or feeling of fullness and reduced desire to eat more in addition to IGF-1, which is required for the metabolism of fat and energy production occurring through Krebs cycle.
25. Topical application of the colostrum constituents has depicted significant promotion for open wound healing. It has been suggested that nucleotides, epidermal growth factor (EGF), transforming growth factor (TGF) and IGF-1 promote cellular and skin growth and also help in repairing DNA and RNA damage.
26. Growth of nerve cells, skin, cartilage, muscle and bone are tissues where colostrum showed beneficial effects.
27. BC (bovine colostrum) was found to reduce NSAID-induced gastric injury and probably by enhancing the growth of intestinal villi possibly due to the action of IGF and TGF-β present.
28. Lactoferrin was also found to be capable of protecting the skin from ultraviolet B (UVB)-induced photo damage.
29. Juvenile diabetes (type-1 or insulin dependent diabetes) is thought to occur through an autoimmune disorder, primarily initiated by an intense allergic reaction to the protein glutamic acid decarboxylase (GAD). Colostrum contains various bioactive factors, which can control and inhibit this autoimmune disorder and other similar allergies.
30. The immunoglobulin IGF-1 found in colostrum can bind to both insulin and IGF-1 receptors present in target cells of human body. Additionally, BC was found to reduce glucose and malondialdehyde levels in alloxaninduced diabetes in rats. A similar model adopted for mice showed that both BC and HBC were able to significantly reduce glucose and lipid levels with HBC being the superior one.
31.  BC-mediated β-cell regeneration leading to insulin release and peroxisome proliferator-activated receptor-α (PPARα) like actions of conjugated isomers of linoleic acid (CLA) could be the mechanisms behind the antidiabetic actions of BC. The antioxidant effect of BC could be mediated by its non-enzymatic components such as lactoferrin and A, C, E vitamins.
32. Lactalbumin present in colostrum is responsible for inducing apoptosis (physiological cell death) of the cancerous cells.
33. Colostrum-derived IgG fractions possess HIV-1 neutralizing activity.
34. It has been demonstrated that patients suffering from distal colitis (a form of IBD) showed marked improvement after taking a colostrum. For such IBD symptoms, the growth factors contained in colostrum stimulate the intestinal cells to repair themselves through proliferation and restitution. The immune and growth factors found in such bovine colostrum are virtually identical to those found in human colostrum, and the immune factors are reportedly four times richer.
35. An additional benefit to bovine colostrum is its special glyco-proteins and protein constituents, which have been shown to be extremely effective in protecting colostrum’s active components from the destructive forces of the human body’s digestive system.
36. Colostrum stimulates the lymphoid tissue providing benefits in aged or immuno- deficient people.
37. Researchers reported that colostrum stimulates maturation of B Lymphocytes (type of white blood cell) and primes them for production of antibodies, enhances growth and differentiation of white blood cells. Similar activity in cow and human colostrum can also activate Macrophages. 
38. Bovine colostrum contains high levels of growth factors that promote normal cell growth and DNA synthesis.
39. A novel mechanism of the immune protection afforded by milk/colostrum is through its numerous anti-inflammatory agents in conjunction with its  inflammatory mediators. This is important because classical immune protection is achieved through the marshaling of inflammation, but this would be fatal in an infant. Therefore it is necessary to modulate the inflammatory response through the action of anti-inflammatory agents.
40.  Rheumatoid arthritis is an autoimmune disease with cytokine involvement.. Infopeptides (colostrum-derived protein derivatives) have been shown to reduce inflammation, edema, pain and fever regardless of cause. A clinical trial was carried out to study the effects of these Infopeptides on rheumatoid arthritis (RA) as well as therapy-resistant osteoarthritis (OA). Both RA and OA patients showed significant improvement after supplementation with the Infopeptides with sustained benefit and improvement on prolonged therapy. Aside from the clinical benefits, this treatment regimen has the benefit of oral administration, low cost and an absence of side effects.
41.  Colostrum creates stem cells. Colostrum also contains preformed growth factors and cytokines that may support activation of the bone marrow stem cell niche directly following absorption into the bloodstream. It also contains other proteins that may stimulate the stem cell niche indirectly via activation of the innate immune system. Colostrum activates stem cells through GCSF (granulocyte colony stimulating factor) and IL-6 (interleukin-6), important cytokines involved in stem cell release and maintenance of “stem-ness” or pluripotency as well as cell migration, whilst VEGF (vascular endothelial growth factor) is an important migratory and engraftment factor for stem cells at sites of tissue damage.
42. Colostrum was shown to induce GCSF, IL-6 and VEGF in a dose-responsive manner indicating that bovine colostrum can reliably induce cytokines that are known to be associated with increased bone marrow stem cell activities such as release from the stem cell niche, migration and engraftment.
43. Colostrum has unique adaptive strategies in either modulating an overactive or bolstering a weak immune response. However, BC differentially affected stimuli-induced IFN-gamma production: it enhanced IFN-gamma in response to weak antigenic stimulation and it inhibited IFN-gamma in response to strong antigenic stimulation. These effects were not dose-dependent.
44. The structure and properties of a new immunomodulatory peptide isolated from ovine colostrum are described. PRP acts both in vivo and in vitro…It can simultaneously change surface markers and function of cells.
45. A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific……Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies.
46. In particular, PRP was shown to recruit suppressor T cells in a model of T cell-independent humoral immune response and suppressed autoimmune hemolytic anemia in New Zealand Black mice. Subsequent in vitro studies in the human model revealed that CLN regulated mitogen-induced cytokine production in whole blood cultures. A discovery that CLN promoted procognitive functions in experimental animal models, supported by other laboratory findings, indicating prevention of pathological processes in the central nervous system, led to application of CLN in multicenter clinical trials. The trials demonstrated the therapeutic benefit of CLN in Alzheimer’s disease (AD) patients by delaying progress of the disease.
47. Russia 2010 The world scientific community is unanimous in the opinion that lactoferrin, a bactericidal protein from human breast milk and colostrum, can break the vicious circle of the antibiotic-related problems.
48. Bulgaria June 2015 The discovery that it is possible to transfer cell-mediated immunity (CMI) to  recipients by leukocyte derivatives gave a new opportunity to medicine. Since CMI is crucial for controlling infections, as well as cancer, autoimmune diseases, immunodeficiencies and allergies, TF (Transfer Factor) can be used in the prophylaxis and treatment of these diseases.
49. The main function of SIgA is to exert immune exclusion; that is, by intimate cooperation with innate nonspecific defense factors it decreases penetration of soluble antigens and inhibits epithelial colonization of bacteria and viruses…..SC represent the “lock and key”in the glandular transport.
50. In adults ingesting bovine anti-Clostridium difficile immunoglobulins, toxin-neutralizing activity paralleled the bovine IgG content in ileal effluent, and in stool samples. A pepsin-resistant form of bovine IgG representing approximately 10% of colostral immunoglobulin has been isolated with a lectin that binds O-linked oligosaccharides, indicating that some proportion of IgG in the gastrointestinal tract may remain intact.
51. Lactoferrin, an iron-binding glycoprotein, is a cell-secreted mediator that bridges innate and adaptive immune function in mammals. It is a pleiotropic molecule that directly assists in the influence of presenting cells for the development of T-helper cell polarization. 
52. There is emerging evidence that many mediators originating from the myeloid lineage revive immune homeostasis in most insult-induced metabolic disparity  Thus, the utility of such immune mediators represents a novel therapeutic approach that depends on immunopotentiation, immunosuppression, or induction of immunological tolerance. Lactoferrin is one of these mediators that naturally bridge the innate and adaptive immune functions by regulating target cell response, including those involved in oxidative stress and systemic inflammatory responses (SIRS). It is also recognized as a significant contributor in regulation of antigen presentation and development of productive T helper cell response. Engagement of innate components leads to triggering of signal pathways to promote inflammation, ensuring that invading pathogens remain in check while the specific immune response is either generated or upregulated. Lactoferrin is a key molecule involved in these processes.

53. Lactoferrin is considered a first-line defense protein involved in protection against a multitude of microbial infections and prevention of systemic inflammation.  Lactoferrin also exhibits direct effects on pathogens . These include bacteriostatic and bactericidal effects, the former being a result of iron sequestration by lactoferrin and the latter dealing with lactoferrin capabilities to bind lipopolysaccharide (LPS).
54. The ability of lactoferrin to bind large quantities of iron also provides protection against pathogens and their metabolites by enhancing phagocytosis and cell adherence and controlling the release of proinflammatory cytokines. Other direct effects of lactoferrin include anti-viral, anti-parasitic, and anti-fungal activities. Additionally, lactoferrin possesses indirect activity, often through prevention of pathogen invasion by blocking interaction with receptors used for entry on host cells.
55. Lactoferrin is a critical component involved in mediation of this response, so as to allow controlled regulation of inflammation without rapid induction of pathological damage. The mechanism of action for lactoferrin contains multiple components for differential regulation of cellular immune responses during the development of SIRS (systemic inflammatory responses) (SIRS).
56. Direct effects of lactoferrin include anti-viral, anti-parasitic, and anti-fungal activities. Additionally, lactoferrin possesses indirect activity, often through prevention of pathogen invasion by blocking interaction with receptors used for entry on host cells.
57. Lactoferrin is able to facilitate restoration of the immune response.
58. Lactoferrin can act on B cells, a known antigen presenter, to allow subsequent T cells interactions that favor elevation of the antibody response.
59. Clinical trials with BCC provide evidence that oral application reduces the influx of LPS from the gut and this appears to be a major mechanism underlying its therapeutic effect in patients at risk for Gram-negative septic shock; data from two well-controlled clinical studies with a total of 100 surgical patients have shown that the inhibition of intestinal LPS absorption measured after the application of BCC not only reduced the LPS levels in the peripheral blood but also inflammatory parameters like IL-6 and CRP were found to be diminished.
60. The present invention is directed to lactoferrin for use in the treatment of severe sepsis. In particular, the present invention is directed to a method for treating prophylatically or therapeutically severe sepsis. Further, septic shock or related conditions such as multiple organ failure and acute respiratory distress syndrome (ARDS) can be treated with lactoferrin. According to the invention it was found that severe sepsis can be successfully treated with oral lactoferrin. Severe sepsis is defined as sepsis plus one or more organ dysfunctions.
61. The present invention relates to methods of using lactoferrin (LF) to reduce circulating levels of cholesterol and vascular inflammation, in order to treat, prevent or reduce the incidence of atherosclerosis and cardiovascular disease.
62. We hypothesized that lactoferrin regulates PHD2 expression and enzymatic activity, and the PHD2 regulation promotes HIF-1α stability and prevention of neuronal cell death mediated by prion protein (PrP) residues (106–126). Lactoferrin prevented PrP (106–126)-induced neurotoxicity by the induction of PrPc expression via promoting HIF-1α stability in neuronal cells. Our results demonstrated that lactoferrin prevented PrP (106–126)-induced neurotoxicity via the up-regulation of HIF-1α stability determined by PHD2 expression and enzymatic activity. These findings suggest that possible therapies such as PHD2 inhibition, or promotion of lactoferrin secretion, may have clinical benefits in neurodegenerative diseases, including prion disease.
63. Lactoferrin is rapidly emerging as a natural bone building factor. A recent study by researchers at the University of Auckland in New Zealand found that: “At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area.”
64. The invention relates to the Proline-Rich Polypeptide complex (PRP) derived from the mammalian colostrum for use in the treatment of the disorders and conditions related to the alterations of the Brain-Derived Neurotrophic Factor level as well as modulation thereof, particularly disorders and conditions wherein therapeutic strategy is based on the increasing of the BDNF concentration in blood. The PRP complex is postulated to be used for nutrition of adults, young children/babies and infants to promote and preserve the proper development and function of both immune and nervous system. PRPs may be used for supplementation of modified milk and infant milk formulae to make it closer to breast milk.
65. It has been well documented in the art that mammalian colostrum is a rich source of health-enhancing components including the immune system supporting factors. Colostrum, the pre-milk fluid produced by mammals during the first 72 hours after birth, contains a high concentration of various constituents, e.g. nutritional factors, immunoglobulins, growth factors, cytokines and the specific immune cells, such as lymphocytes T, lymphocytes B, neutrofiles, and macrophages.
66. Proline-Rich Polypeptide complex stimulate blood cells to release the key immune system cytokines, eg., ΪΝΡ-γγ, TNF-α, IL-6, and IL-Ιβ, thus boosting or inhibiting the immune system (restoring the homeostasis). Moreover, the PRP preparations could accelerate the maturation and differentiation of murine thymocytes to active lymphocytes.
67. In vivo studies have proved also the psychotropic activity of the Proline-Rich Polypeptide complexes. The administration of Proline-Rich Polypeptide complex boosted cognitive functions in aged rats and was shown to facilitate acquisition of spatial learning and improved incidental memory in aged rodents in the manner similar to that observed in the young animals.
68. Anti-oxidative activity of the Proline-Rich Polypeptide complex is well documented. Results from several studies indicate that PRPs inhibit nitric oxide (NO) formation in cell culture and decrease the generation of intracellular reactive oxygen species (ROS) and oxidative stress, retarding the aging process and protecting from neuronal loss. Both, in vitro and in vivo studies have shown that PRPs significantly decelerate the senescence of cultured cells and extends the lifespan of cells isolated from senescence-accelerated mice. It was documented that PRPs may delay the cellular aging proces by decreasing sequence alterations in DNA in human and in Chinese hamster cell cultures. Further studies have revealed that PRPs show an antimutagenic action in cells stressed oxidatively or exposed to two chemical mitotic agents, methyl methanesulfonate and mitomycin C, commonly used in cancer treatment.
69. Proline-Rich Polypeptide complex decreases UVA- and UVB-induced mutation frequency responsible for development of malignant melanoma and squamous cell carcinoma, respectively.
70. These data along with the well-documented high immunotropic activity of colostrinin in vitro in blood samples of patients with numerous disorders may suggest the possible usage of the Proline-Rich Polypeptide complex as an active agent to treat chronic diseases with a bacterial and viral etiology, and acquired immunological deficiencies in the aftermath of chemo- and radiotherapy.
71. Oral pharmaceutical compositions of colostrinin as a dietary supplement for the treatment of infants, children and adults undergoing the chemotherapy and/or adults suffered from cachexia or chronic disorders-evoked excessive loss of body weight.
72. Colostrinin-derived peptides sequences, the said peptides being useful, inter alia, in the treatment of disorders of the immune system and the central nervous system.
73. Colostrinin, constituent peptides thereof, and proline rich active analogues of colostrinin are described as promoters of neural cell differentiation, e.g. pluripotent cells of the nervous system, in vitro and in vivo. Using PC 12 cells, it has been investigated the infiuance of colostrinin and its analogues to convert the damaged neuronal cells to functional neurons, process being strongly associated with the neuronal cell differentiation accompanied by the neurotrophic factors production, including Nerve Growth Factor (NGF).
74. Colostrinin for prevention and/or treatment of obesity and obesity-related comorbidities, including type II diabetes mellitus, hypercholesterolemia, atherosclerosis, coronary heart disease, stroke, infammatory conditions, such as, but not limited to, irritable bowel syndrome, infammatory bowel disease, including Crohn’s disease. These beneficial therapeutical effects were assigned to the colostrinin-dependent regulation of the gene expression of both, leptin and resistin, in cells.
75.  Enrichment of the infant milk formulae with Proline-Rich Polypeptide complex, especially with Proline- Rich Polypeptide complex free of IgG, decides to its additional beneficial effect on the immune system of babies, involving immunomodulation, the general immunity improvement, anti-allergic effects, and protection from the autoimmunoaggression.Nutritional composition of CMF according to the present invention is far more beneficial for babies’ health than regular milk formulae available on the market as enrichment of the infant formula with PRPs increases the circulating BDNF concentration similarly to the BDNF level detected in the blood of only breastfed babies.

76. Another aspect of the invention provides the Proline-Rich Polypeptide complex for use as a nutritional additive for pregnant women, in order to increase the BDNF level in the blood of a mother and a baby. The pregnant women diet enriched with PRPs contributes to the activation of immunomodulatory and anti-allergic pro cesses s as well as leads to the improvement of the general immunity.

77. Further aspect of the present invention provides Proline-Rich Polypeptide complex for use as a nutritional additive for older babies after breastfeeding and/or after milk formula feeding, and for adults, in order to induce and/or enhance the activity of nervous system and/or to achieve the pro-cognitive effect, ie. the memory and concentration improvement.

78. The unique composition of the modified infant milk formula enriched with bovine-derived Proline-Rich Polypeptide complex that makes it closer to breast milk is hereinafter referred to as Coloco Mathernized Formula (CMF). The novel composition of CMF shows the unique properties to increase the BDNF level in the infants’ blood.