GROWTH FACTORS: IMPLICATIONS IN HEALING AND PHYSIOLOGY

Dohm, G. Lynis, et al, Sept. 1990, Diabetes Vol, 39. "IGF-1--Stimulated Glucose Transport in Human Skeletal Obesity and NIDDM." "Based on the observation that insulin-like growth factor 1 (IGF-1) can stimulate glucose utilization in non-diabetic subjects... IGF-1 might provide an effective acute treatment for the hyperglycemia of NIDDM." "Presence of IGF-1 receptors in human muscle, with IGF-1 binding being 24% that of insulin. There was no change in IGF-1 bind in muscle from obese or diabetic subjects..." "IGF-1 stimulated glucose transport approximately twofold..."

Mero, Antti; et al. The Dept. of Biology of Physical Activity, Univ. Of Jyvaskyla, Finland. The American Physiological Society. 1997. Effects of bovine colostrum supplementation on serum IGF_1, IgG, hormone, and slaiva IgA during training. Bovine colostrum supplement increased serum IgF-1 concentration in athletes during strength and speed training.

Antonio, PhD, CSCS, Jose. Muscle & Fitness. May 1998. BODY BUILDING SCIENCE – From the Weider Research Group. Can Bovine Colostrum Enhance Levels of IGF-1? Studies indicate that bovine colostrum supplementation can increase levels of IGF-1.

Gil, Angel, Sanchez-Medina, 1981, Journal of Dairy Research, Vol 48 Vol. pp 35-44. "Acid Soluble Nucleotides of Cow’s, etc.": Bovine Colostrum was found to contain seven different nucleotides which are important for normal cell function and repair.

Ballard, Neild, Francis et. al., 1982, Journal of Cellular Physiology, 110 pp 249-254. "The Relationship Between the Insulin Content and Inhibitory Effects of Bovine Colostrum on Protean Breakdown": Insulin-like ingredient in bovine colostrum (IgF-1) slows protein breakdown. Protein breakdown was also slowed by addition of colostrum to a cell line known to be unresponsive to insulin, indicating the presence of non-insulin growth factors in bovine colostrum.

Sporn, et. al., 1983, Science, 219 pp. 1329-31: "Polypeptide Transforming Growth Factors (TGF A & B) and Epithelial Growth Factor Isolated from Bovine Colostrum Used for Wound Healing in Vivo" : Growth factors in bovine colostrum were found to be very effective in promoting wound healing. Implications for trauma, and surgical healing. External and internal applications implied.

Ballard et. al., Biochem J. 1983 V 210, 243-249: Effects of anabolic agents on protein breakdown: "Protein degradation is inhibited by bovine colostrum. Anabolic agents such as trenbolone, diethylstilboestrol, and testosterone do not alter rates of intercellular protein breakdown."

Ballard, Francis, Geoffry, 1983, Journal of Biochemistry, Vol. 210 pp. 243-249: "Effects of Anabolic Agents on Protein Breakdown in L6 Myoblasts": Describes how protein breakdown in tissue due to injury is inhibited by several anabolic agents especially an insulin-like substance (IgF-1) found in bovine colostrum.

Noda, et. al., 1984, Gann, Vol. 75, 109-112. Japanese researchers discovered that Transforming Growth Factors A and B (TGF A & B) in bovine colostrum were involved in normal cellular activities such as embryonic development, cell proliferation, and tissue repair. They also reported it promoted the synthesis and repair of DNA - the master code of the cell.

Francis, 1986, Biochemical Journal, 233(1) pp. 207-213; "Purification and Partial Sequence Analysis of Insulin-like Growth Factor 1 from Bovine Colostrum" Showed Bovine IgF-1 to be identical to human IgF-1. Described purification process for extraction of IgF-1 from colostrum.

Roberts, Sporn, Assoian, et. al., 1986, Procedures of the National Academy of Sciences, Vol..83, pp. 4167-71: "Transforming Growth Factor Type B: Rapid Induction of Fibrosis and Angiogenisis in Vivo and Stimulation of Collagen Formation in Vitro" Ristow, et al., pp. 5531-5533 Reports BSC-1 growth inhibitor type B transforming factor is a strong inhibitor of thymocyte (T-lymphocyte precursor) proliferation ( presence in bovine colostrum confirmed: Noda, 1984)

Seyedin, Thompson, Bentz, et. al., 1986, Journal of Biol. Chemistry, Vol. 261, pp. 5693-95: Reported Cartilage Inducing Factor-A in colostrum and its apparent affinity to Transforming Growth Factor B (in human and bovine colostrum), and its relationship to cartilage repair.

Francis, GL, et al. 1988, Biochem J., 251: 95-103. Insulin-like growth factors 1 and 2 in bovine colostrum. "...The sequence of bovine IGF-1 was found to be identical with that of human IGF-1,..."

Francis, Upton, Ballard, McNeil, 1988, Journal of Biochemistry, Vol. 251: 95-103 (printed in Great Britain): "Insulin-Like Growth Factors 1 & 2 in Bovine Colostrum": Two growth factors similar to insulin were purified from bovine colostrum IgF-1 found to be identical to the corresponding human growth factor. In this experiment protein synthesis was increased and protein breakdown was reduced by administration of the bovine colostrum extracts.

Oda, Shinnichi, et. al., 1989, Comparative Biochemical Physiology, A: Comparative Physiology, Vol. 94A No 4 pp. 805-808: "Insulin-Like Growth Factor 1, GH, Insulin and Glycogen Concentration in Bovine Colostrum and in Plasma of Dairy cows": Bovine colostrum contains high levels of growth factors that promote normal cell growth and DNA synthesis.

Tollefsen, Lajara, McCusker, Clemmons, 1989, Journal of Biological Chemistry, Vol. 264 No 23, Aug. 15: " Insulin-Like Growth Factors (IgF) in muscle Development": IgF’s role in differentiation, repair, synthesis, and their interplay with other necessary growth factors. IgF-1 only factor that can stimulate muscle growth and repair by itself. Eliminates catabolism and stimulates anabolism at the cellular level.

Tollefsen, Sherida E, et al. 1989, The Journal of Biological Chemistry, Vol. 264, No 23, August 15, Insulin-like Growth Factors (IGF) in Muscle Development. "...Studies demonstrate that several components critical to IGF action are produced in a a fusing skeletal muscle cell line in a differentiation-dependent manner and suggest that both IGF-1 and IGF-2 may be autocrine factors for muscle."

Watson, Dennis L, et al. 1990, Journal of Dairy Research, 59, 369-380, Factors in ruminant colostrum that influence cell growth and murine IgE antibody responses. "We conclude that bovine colostrum contains cell-growth factors as well as immunomodulatory factors that are able to regulate the IgE response in a heterologous species."

Allen and Rankin, 1990, PSEBM Vol. 194, Muscle Biology Group, Dept. of Animal Sciences and Physiology, Univ. of Arizona, Tucson, AZ. Reported: A. Fibroblast growth factor (FGF) stimulates proliferation but depresses differentiation of muscle cell growth. B. Insulin Like Growth Factor (IGF-1) stimulates both. C. Transforming Growth Factor (TGF-b) slightly depresses proliferation and inhibits differentiation. Conclusion: When administered in combination these factors induce satellite cells to grow, regenerate and proliferate. Following, these cells will fuse with one another or the adjacent muscle fiber thereby increasing myonucles numbers for growth and repair. All three Factors found in Bovine Colostrum

Ullman, et al. Acta Physiol Scand. 1990 v 140 p 521-5: Effects of Growth Hormone on muscle regeneration and Igf-1 concentration in old rats: "High age is associated with reduced levels of GH and IgF-1. Administration of growth hormone raises level of IgF-1 to that of young rats. With increased IgF-1 the reduced protein synthesis of old rats is restored, caused increased muscle tissue in normal and regenerating muscle tissue, and increased maximum contraction force."

Patureau- Mirand, Posone, Levieux, Attaix, et. al, 1990, Biol. Neonate Vol. 57(1): 30-6 Reported that Colostrum stimulated intestinal protein synthesis.

Skottner, Arrhenius-Nyberg, Kanje and Fryklund, 1990, Acta Paediatric Scand. (suppl) 367: 63-66, A. IGF-1 resulted in significant body weight gain and significant bone growth. B. Topical administration to wounds resulted in more effective healing. C. Stimulated nerve regeneration

Dohm, Elton, Raju, Mooney, Pories, Flicklinger, Atkinson, 1990, Diabetes 39: 1028-32, Reported that: A. IGF-1 Stimulates glucose utilization. B. IGF-1 receptors in muscle tissue is normally occurring in humans. C. IGF-1 effective treatment for Hyperglycemia

Tokuyama H, et al. Growth Factors, 1990, Vol. 3, pp. 105-114, "Isolation of Two New Proteins from Bovine Colostrum Which Stimulate Epidermal Growth Factor-Dependent Colony Formation of NRK-49F Cells" "...results suggest that BC-1 and BC-2 belong to a new class of mitogen/inhibitors."

Thissen, et. al. Endocrinology, 1991 V 129 p 429-35: Evidence that pretranslational and translational defects decrease serum IGF-1 concentrations during dietary protein restriction: " Dietary protein restriction causes GH (growth hormone) resistance and decreases IGF-1 serum levels." (Implications in loss of muscle mass related to protein depravation).

Marcotty et. al., Growth Regulation 1991 Longman Group UK: IgF-1 from cow colostrum: Characterization: "IgF-1 potent stimulator of growth and differentiation of numerous cell types. Bovine sequence identical to Human IgF-1

Lundeberg, et.al. W.B. Saunders Co. 1991: Growth Hormone improves Muscle Protein Metabolism: " Human Study indicated: GH prevented catabolism in muscle and improved whole body nitrogen economy. Investigations of the possible beneficial effects of GH to prevent skeletal muscle deterioration after surgical trauma are advocated."

Breese, et. al., Jour. Gerontology (aging) 1991 V 46 p B180-7: Influence of age and long term dietary restriction on IGF-1: "Study of relationship of IGF-1 and lifespan: Demonstrated a decrease in relative IGF-1 concentration with age , as well as dietary restriction. Indicates aging associated with reduced levels in plasma IGF-1 and other GH levels." Implications as antiaging.

Bak, Jens Friis, et al. Am. J. Physiol. 260 (Endocrinol. Metab. 236): E736-E742, 1991, et al. "Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans" "...GH inhibited the insulin-stimulated glucose disposal by 27%... and raised the non protein energy expenditures..." "...GH 1)increases energy expenditures and inhibits glucose oxidation in favor of an increased lipid oxidation, and 2)inhibits insulin-mediated activation of the glycogen synthase in skeletal muscle biopsies..."

Bricker, BS, Daniel S. The American Chiropractor, Nov. 1991. COLOSTRUM: Implications for Accelerated Recovery in Damaged Muscle and Cartilage, Prevention of some Pathogenic Disease. Bovine colostrum contains unsurpassed repair characteristics for muscle and cartilage.

Schwade, Steve. Muscle & Fitness. May 1992. INSULIN-LIKE GROWTH FACTORS. This Potent Growth Stimulant Found in Mother’s Milk May Help Big Boys Grow Bigger. Human muscle cells have a high affinity for IGF-1.

Resnicoff, Sell, et al. Jour. Biol. Chem. 1993, v 268 p 21777-82: Ethanol inhibits autophosphorylation of IGF-1 receptor and IGF-1 mediated proliferation: "Findings demonstrate that ethanol at low concentrations markedly inhibits IGF-1 receptor autophosphorylation and IGF-1 mediated cell growth."

Chaumeil, Liolet, Kogbe, 1994, Adv Exp. Med. Biol. Report of clinical study Vol. 350 pp. 595-599 Reported effective treatment of eye infections with bovine colostrum lactoserum i.e.: reduction in glaucoma, scaring after injury or surgery, reduction in eye lesions.

Stokes, Joseph 1994, Children’s Hospital, Philadelphia, Am. J. Physiol. "Insulin-like growth factors (IGF’s) mediate cell proliferation and differentiation and bind with high affinities and specificities to IGF receptors and IGF-binding proteins (IGFBP’s)." "...IGF’s are mitogens for cultured rabbit ASM cells and their actions are most likely mediated through the type 1 IGF receptors. The ASM cells secrete IGF-II and IGFBP-2, and the latter could modulate the actions of the IGF’s in these cells.

Xu, Mardell et. al., Immunology 1995 vol 85 p 394-9: Expression of functional IgF-1 receptor on lymphoid cells: " Our studies suggest that biological activities of IGF-1 include direct stimulation of immune cells and that expression of IGF-1 receptor may have a role in the regulation of T-cell function."

Bhora, et. al. Jour. Surg. Res. 1995 V 59 p 236-44: Effect of growth factors on cell proliferation in human skin.: "The failure of chronic wounds to heal is a major medical problem. Studies suggest an important role for growth factors in promoting wound healing. Conclusion: Fibroblast growth factor IGF-1 and epithelial growth factor are important for wound healing." Treatment implications for trauma and surgical wounds, accelerated healing possible.

Bak, Moller, Schmitz, Medical Endocrinological Dept III, University Clinic of Internal Medicine, Aahus Kommunehospital, Aarhus, Denmark: GH inhibited the insulin stimulated glucose disposalby 27% and raised nonprotein energy expenditures Fat Oxidation contributed 71.7% of Energy expenditures during GH administration as compared with 48% without. Conclusion GH increases energy expenditures and inhibits glucose oxidation in favor of increased lipid (fat) oxidation (burning)."

Gluckman, Breir and O’Sullivan, Dept. of Pediatrics, Univ. of Auckland, New Zealand: A. IGF-1 inhibits malnutrition induced catabolism. (If actively present IGF-1 stops the burning of body proteins, {muscle} for energy)

Ullman, Sommerland, Skottner, Dept. of Pathology and Pharmacology, Univ. of Gothenburg, Sahlgren Hospital & HabiVitrum AB, Stockholm, Sweden: A. High age associated with reduced levels of GH and IGF-1. B. Induction of GH and IGF-1 increase body weight through muscle growth of aged subjects

Rosenthal, Brown, Brunetti and Goldfine, Dept. of Pediatrics, Univ. of California, SF Div. of Diabetes and Endocrine Research, Mount Zion Medical Center, Univ. of Ca., SF A. Presence of FGF (Fibroblast Growth Factor) (in bovine colostrum) inhibits IGF-II’s ability to decrease IGF-1 receptors in muscle tissue resulting in a 60-70% increase in IGF-1 binding.

Pakkenen, R; Aalto, J. International Dairy Journal. 1997. Review Paper: Growth Factors and Antimicrobial Factors of Bovine Colostrum. Colostrum is rich in nutrients, antibodies and growth factors. Colostrum contains insulin, transforming growth factor b and related growth factors. Growth factors promote the growth and development of the newborn... while antimicrobial factors provide passive immunity and protect against infections...

Klagsbrun, 1978, Proceedings of the National Academy of Sciences, 75, pp.; 5057-5061. "Human Milk Stimulates DNA Synthesis and Cellular Proliferation in Cultured Fibroblasts": Growth Factors in milk showed 100 times the potency of serum when tested on fibroblasts.

Shimizu, Webster, Morgan, Blau and Roth, 1986, American Physiological Society , Dept. of Pharmacology, Stanford University, School of Medicine: A. Presence of IGF-1 Receptors in human muscle cells confirmed.

Tomas, Knowles, Owens, Read, Chani, Gargosky and Ballard, 1991, Biochem Journal Vol. 276. pp. 547-554. Reported: A. Igf-1 peptides stimulate muscle protein synthesis and improve nitrogen balance. B. des (1-3) IGF-1 is at least as potent as the full length IGF-1. C. Bovine Colostrum is natural source of both factors.