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This paper is intended to provide scientific and educational information only. It is not intended for use to promote or sell any product. The statements herein have not been evaluated by the Food and Drug Administration. Consumption of RPM Factors™ is not intended to diagnose, treat, cure, or prevent any disease. The research discussed is generally preliminary in nature. Further research is warranted. 2010© by Sterling Technology. All rights reserved. Sports Nutrition Support Through Concentrated Bioactive Whey Protein www.sterlingtechnology.com 800.522.3699 www.wildflavors.com 888 WILD Flavors
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Page 1: Sports Nutrition Support Through Concentrated Bioactive ... · sports groups is remarkable. Improvement in lean body and body fat reduction even among professional athletes is also

This paper is intended to provide scientific and educational information only. It is not intended for use to promote or sell any product. The statements herein have not been evaluated by the Food and Drug Administration. Consumption of RPM Factors™ is not intended to diagnose, treat, cure, or prevent any disease. The research discussed is generally preliminary in nature. Further research is warranted.

2010© by Sterling Technology. All rights reserved.

Sports Nutrition Support Through Concentrated Bioactive Whey Protein

www.sterlingtechnology.com 800.522.3699 www.wildflavors.com 888 WILD Flavors

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A Sports nutrition ingredient opens an opportunity for growth

Recover faster Perform better Mobilize strength

Training the body to be faster, better and stronger can be beneficial. With over 20 million participants and gaining serious mainstream traction, the rise of high-intensity interval training from fitness pros, elite coaches to beach-body boot camps are upping intensity and shortening workouts to get consumers better health and fitness results.

Athletic activity and exercise is typically associated with muscle stress and immune depletion. Such exercise related fatigue can be reduced by nutritional factors such as whey proteins. However, immune related fatigue cannot be adequately addressed by dietary factors alone. RPM Factors™ is a colostrum based whey protein concentrate which is not only rich in whey proteins but it is also rich in immune bioactives such as Immunoglobulin, Lactoferrin and Proline Rich Peptides.

The related stress of high-intensity exercise, along with competitive training can produce inflammatory immune cascade which may result in respiratory symptoms such as sore throat, fatigue and longer recovery times after strenuous workouts.(1) This is mainly due to inadequate anti-inflammatory response by the host immune system against the inflammatory cascade initiated by stressor events (including intense exercise sessions). High intensity training regimens can set-off upper respiratory tract infections. Research has reported that 17.8% of athletes miss a practice and 5.1% miss a competition due

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to illness associated with increased bouts of intense strength and endurance training.(2)

In addition to immune health being a concern, gastrointestinal problems are more likely to occur with the increase of exercise intensity.(3) It is estimated that incidence rates of gastrointestinal issues can range from 20-50% among endurance athletes.

RPM Factors™ is a unique whey protein that has been

micro-filtered to be specifically rich in concentrated

peptides and growth factors researched for their health

and fitness benefits.

Bioactive Purpose RPM

Factors™ Whey Protein Concentrate

Immunoglobulin G Immune and gastrointestinal support

40% 5%

Immunoglobulin A 1.1 % 0.2 %

TGF-β2 Cell growth, proliferation and differentiation

140μg/ 100g 8μg/100g

IGF-1 Anabolic effects 120μg/ 100g 5 μg/100g

Proline Rich Peptides Main regulator of cell systems

3 % 1 %

Lactoferrin Binding and transport of iron ions, antibacterial

functions

500-700mg/ 100 g

30mg/100 g

Sialic Acid Viral inactivation, cognitive function, immune activation

1000-1200mg/ 100g

150-300mg/ 100g

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RPM Factors™ is an ideal solution for reducing discomfort

and negative effects associated with intense strength and

endurance building.

Specific immunoglobulin and peptide concentrations in

RPM Factors™ are shown to increase migration and repair

of challenged epithelial cells and stimulate mucous

production on the gut lining thereby building a stronger

barrier against pathogens. (4) - (8)

RPM Factors™ also contains a substance known as

proline-rich polypeptides that have the ability to

modulate the immune response by either turning up an

underactive immune system or turning down and

overactive one. (9)- (11)

Biological Effects of Proline-Rich Polypeptides(12)

Promotion of T cell maturation (13) - (18) (19)

Helper activity in T cell-dependent immune response (13) (15) (17) (18)

Induction of suppressor cells in T cell-independent immune response (20)

Mitogenic activity (17) (18)

Suppression of the autoimmune response (21) (20)

Regulation of cytokine production in vitro and in vivo in humans (22)

Antimutagenic properties (23)

Antioxidant properties (24)

Enhancement of cognitive processes in animals (25) - (27)

Prevention of pathological processes in the central nervous system (28) -(30)

Clinical Trials (31) - (33)

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There are over 30 published studies demonstrating

performance and strength attributes associated with

the consumption of bovine colostrum by athletes:

• Faster runs Increased peak running speed Improved running performance Enhanced sprint performance

(34) - (36) • Better jumps Increased peak vertical jump

Improved jump performance (36) (37)

• Faster times Improved time-trial performance, intensity and peak cycle power (38) -(40)

• Elevated mass and strength

Increased lean body mass, resistance exercise and repetitions (37) (41)- (43)

The review of this research led to examination of

whether oral consumption of RPM Factors™ could

support enhanced athletic performance among athletes

in the face of exercise induced stress. In a consumer

study, RPM Factors™ was ingested by 92 athletes over a

period of 3 months during which self reported outcomes

were recorded. Study participants reported a significant

improvement in athletic performance. RPM Factors™ is

safe, well-tolerated, and improves athletic outcomes in

exercise-stressed individuals.

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Study Design

RPM Factors™ was supplied to Sports Performance

Group, at Rockville Center, New York. The consumers

included high school and professional athletes (36 Male,

55 Female ages 17 - 25) from a variety of disciplines

including soccer, softball, volleyball, track and field,

basketball, baseball and lacrosse. RPM Factors™ was

provided in a capsule form and the athletes were given

instructions to consume two capsules daily, which is

equivalent to 1 gram of RPM Factors™ per day. Results of

the three monthly time-points were compared either to

baseline or considering zero day as internal control. Body

fat was also monitored throughout the study.

Health Questionnaire

A self reporting questionnaire was administered as per

protocol developed by Jude Massillon Group. The

questions included how each athlete felt their energy

level, alertness and focus at day zero and up to 6 weeks.

The questions also included feeling of fatigue at day zero

and up to 6 weeks. The ratings were from 1 to 5 with 1

being very low and 5 being very high with 2, 3 and 4 as

low, average and high, respectively.

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Results and Discussion

The role of colostrum and colostrum based bioactives

has attained increased attention due to their perceived

role in positive health outcomes. Many experts believe

that positive health is heavily influenced by how our body

tackles immune related inadequacies triggered by

varieties of stresses including life style and exercise

induced stress. Bioactives that can provide anti-

inflammatory effect can nullify stress related

inflammatory negative health consequences.(42) RPM

Factors™ was tested among young athletes to measure

exercise related positive health improvements. Results of

the study demonstrated general improvement in energy

level, alertness and focus among all the athletes after

intense exercise. All the athletes experienced a reduction

in body fat as well.

Metabolic endpoints were not included in this consumer

trial, however, meta analysis of similar studies performed

on athletes coupled with known effects of colostral

bioactives on immune balancing (from an inflammatory

state to an anti-inflammatory state) indicates a positive

correlation of RPM Factors™ consumption with improved

athletic performance. It is known that exercise related

stress could lead to depressed immune system due to an

inflammatory immune cascade ensuing stress activity.

Bioactives such as Immunoglobulin G, Immunoglobulin A,

Lactoferrin, IGF-1 and TGF-B2 have functionality, as shown

in a multitude of other studies, to tilt the immune balance

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in favor of anti-inflammatory from inflammatory immune

stress environment.

Conclusion

RPM Factors™ is a promising bioactive for intended

sports performance applications. The fact that athletes

experienced marked improvement in alertness, focus and

energy level across all the genders and across all the

sports groups is remarkable. Improvement in lean body

and body fat reduction even among professional athletes

is also quite noteworthy. RPM Factors™ is an efficacious

bioactive and its application in sports nutrition, athletic

performance would be beneficial.

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References 1. Emerging paradigms in immunonutrition. Ebenezer, S. 2011, Topics in Companion Animal Medicine, pp. 26(1); 25-32.

2. Literature review: upper respiratory illness and sport and exercise. Weidner, TG. 1994, Int J Sports med, pp. 15 (1) 1-9.

3. Potential benefits and hzards of physical activity and exercise on the gastrointestinal trace. Peters, HPF., et al. 2001, Gut, pp. 48; 435-439.

4. Carter, S and Jensen, G. Report 9B: Long-term effects of Tegricel in vivo. Klamath Falls, OR : NIS Labs, 2011.

5. The nutriceutical bovine colostrum truncates the increase in gut permability caused by heavy exercise in athletes. Marchbank, Tania, et al. 2011, Am J. Physiol Gastrointestinal and Liver Physiology, pp. G477-G484.

6. Playford, RJ. Confidential report to Sterling Technology. London : Department of Gastroenterology, Hammersmith Hospital, United Kingdom, 2009.

7. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Playford, RJ, et al. 1999, Gut, pp. 44(5): 653-8.

8. Co-administration of the heald food supplement, bovine colostrum, reduces acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Playford, RJ, et al. 2001, Clin Sci, pp. 100 (6): 627-33.

9. A novel extract from bovine colostrum whey supports anti-bacterial and anti-viral innate immune functions in vitro and in vivo. I. Enhanced immune activity in vitro tranlates to improved microbial clearance in animal infection models. Benson, Kathleen F, et al. 2012, Preventive Medicine Journal, pp. 54: Supp S116-23.

10. A novel extract from bovine colostrum whey supports innate immune functions. II. Rapid changes in cellular immune function in humans. Jensen, Gitte S, Patel, D and Benson, K. 2012, Preventive Medicine, pp. 54: Supp S124-129.

11. Proline-rich polypeptide (PRP) - an immunomodulatory peptide from ovine colostrum. Janusz, M and Lisowski, J. 1993, Arch. Immunol. Ther. Exp., pp. 41, 275-279.

12. A Proline-rich polypeptide from bovine colostrum: colostrinin with immunomodulatory activity. Zimecki, M. 2008, Bioactive Components of Milk; Advances in Experimental Medicine and Biology, pp. 606; 241-250.

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13. Proline-rich polypeptide (PRP) from bovine colostrum. Bi-directional modulation of binding peanut agglutinin, resistance to hydrocortisone and helper activity in murine thymocytes. Lisowski, J, et al. 1988, Arch Immunol Ther Exp (Warsz), pp. 36(4) 381-393.

14. Effect of colostrinin, an immunomodulatory proline-rich polypeptide from bovine colostrum, on sialidase and β-galactosidase activities in murine thymocytes. Sokal, I, et al. 1998, Archivum Immunologiae et Therapiae Experimentalis, pp. 46; 193-198.

15. Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a Proline-rich plypeptide (PRP). Wieczorek, Z, et al. 1989, Archivum immunologiae et therapiae experimentalis (Warszava), pp. 37 (3-4); 313-322.

16. The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrolidone (PVP). Zimecki, M, et al. 1983, Arch Immunol Ther Exp (Warsz), pp. 31(6): 895-903.

17. The effect of a proline-rich polypeptide (PRP) on the humoral immune response I distinct effect of PRP on the T cell properties of mouse glass-nonadherent (NAT) and glass-adherent (GAT) thymocytes in the thymectomized mice. Zimecki, M, et al. 1984, Arch Immunol Ther Exp (Warsz), pp. 32(2) 191-196.

18. The effect of a proline-rich polypeptide (PRP) on the humoral immune response II PRP induces differentiation of helper cells from glass-nonadherent thymocytes (NAT) and suppressor cells from glass-adherent thymocytes (GAT). Zimecki, M, et al. 1984, Ach Immunol Ther Exp (Warsz), pp. 32(2) 197-201.

19. Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of IL-1. Zimecki, M, et al. 1987, Archivum Immunologiae et Therapiae Experimentalis, pp. 35; 339-349.

20. Effect of a Proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand black (NZB) mice. Zimecki, M, et al. 1991, Archivum immunologiae et therapiae experimentalis, pp. 39 (5-6); 461-461.

21. Effect of Proline-rich polypeptide on the experimental autoimmune response to erythrocytes. Hraba, T, et al. 1986 , Immunologiae et therapiae experimentalis (Warszava), pp. 34 (4); 437-443.

22. Colostrinin a proline-rich polypeptide from bovine colostrums is a modest cytokine inducer in human leukocytes. Inglot, AD, Janusz, M and Lisowski, J. 1996, Arch. Immunol. Ther Exp, pp. 44, 215-224.

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23. Colostrinin-driven neurite outgrowth requires p53 activation in PC12 cells. Basci, A, et al. 2005, Cell Mol Neurobiol, pp. 25(7) 1123-1139.

24. Modulation of 4HNE-mediated signaling by proline-rich polypeptides from bovine colostrum. Boldogh, I, et al. 2003, J Mol Neurosci, pp. 20(2) 125-134.

25. Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats. Popik, P, et al. 1999, Pharmacol Biochem Behav, pp. 64(1) 183-189.

26. Cognitive effects of colostral-Val nonapeptide in aged rats. Popik, P, et al. 2001, Behavioural Brain Research, pp. 118; 201-208.

27. Enhancement of long-term memory retention by Colostrinin in on-day-old chicks trained on a weak passive avoidance learning paradigm. Stewart, MG and Banks, D. 2006, Neurobiology of Learning and Memory, pp. 86; 66-71.

28. Colostrinin decreases spontaneous and induced mutation frequencies at the hprt locus in Chinese hamster V79 cells. Basci, A, et al. 2006, J Exp Ther Oncol, pp. 5(4) 249-259.

29. Linear quantitation of a beta aggregation using thioflavin T: reduction in fibril formation by colostrinin. Bourhim, M, et al. 2007, Journal of Neurosci Methods, pp. 160(2) 264-268.

30. Protective effect of colostrinin on neuroblastoma cell survival is due to reduced aggregation of beta-amyloid. Schuster, D, et al. 2005, Neuropeptides, pp. 39(4) 416-426.

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

32. Colostrinin proline rich polypeptide complex from ovine colostrum- a long term study of its efficacy in alzheimer's disease. Leszek, J, et al. 2002, Med Sci Monit, p. 8(10) P1930196.

33. Colostrinin™: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of alzheimer's disease. A double-blind placebo-controlled study. Leszek, J, et al. 1999, Archivum Immunologiae et Therapiae Experimentals, pp. 47:377-385.

34. The effect of bovine colostrum supplementation on exercise performance in eleite field hockey players. Hofman, Z, et al. 2002, Int J Sport Nutri Exerc Metab, pp. 461-469.

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35. Effects of oral bovine colostrum supplementation on serum insulin-lik growth factor-1 levels. Kuipers, Harm, et al. 2002, Nutrition, pp. 566-567.

36. Bovine colostrum supplementation enhances physical performance on maximal exercise tests. Leppäluoto, J., et al. Brisbane, Australia : s.n., 2000. Pre-Olympic Congress Sports Medicine and Physical Education International Congress on Sport Science.

37. Effect of bovine colostrum on anaerobic exercise performance and plasma insulin-lik growth factor 1. Buckley, JD, Brinkworth, GD, Abbott, MJ. 2003, Journal of SPorts Seinces, pp. 577-588.

38. Dose effects of oral bovine colostrum on physical work capacity in cyclists. Coombes, JS, et al. 2002, Medicine and Science in Sports & Exercise, pp. 1184-1188.

39. Assessment of anaerobic performance in healthy males after an eight week concentrated bovine colostrum supplementation. O'Leary, L., et al. Dicson : Australia, 2003. Australian Conference of Scienc and Medicine in Sport and Third national Sports Injury Prevention Conference. p. 38.

40. The influence of bovine colostrum supplementation on exercise performance in highly trained cyclists. Shing, CM, et al. 2006, British Journal Sports Medicine, pp. 797-801.

41. The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women. Antonio, Jose, Sanders, Michael S. and Darin, Van Gammeren. 2001, Nutrition, pp. 243-247.

42. Effect of bovine colostrum supplementation on the composition of resistance trained and untrained limbs in health young men. Brinkworth, GD, et al. 2004, European Journal Applied Physiology, pp. 53-60.

43. Impact of differing protein sources and a creatine containing nutritional formula after 12 weeks of resistance training. Kerksick, CM, et al. 2007, Nutrition, pp. 647-656.

44. Proline rich polypeptide from ovine colostrum: its effect on skin permeability and on the immune response . Wieczorek, Z, et al. 1979, Immunology, pp. 36:875-881.

45. Effects of bovine colostrum supplementation on training adaptations I: body composition. Kreider, RB, et al. Orlando, FL : FASEB J., 2001. 85th Annual Experimental Biology. p. 15:LB58.

46. Protein metabolism and strength performance after bocine colostrum supplementation. Mero, A, et al. 2005, Amino Acids, pp. 327-335.

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APPENDIX:

RPM Factor Components

Immunoglobulins (Igs) Bovine serum and lacteal secretions contain three major classes of Igs: IgG, IgM and IgA. The basic structure of all Igs is similar, and is composed of two identical light chains (23 kDa) and two identical heavy chains (53 kDa). These four chains are joined together with disulphide bonds. The complete Ig or `antibody' molecule has a molecular weight of about 180 kDa. Monomeric IgM and IgA have a similar basic structure to IgG except for the addition of a C-terminal octapeptide to the heavy chains. IgA occurs as a monomer or dimer, the latter comprising two IgA molecules joined together by a J-chain and a secretory component. This complex is called secretory IgA (SIgA) and has a molecular weight of about 380 kDa. Except for ruminant lacteal secretions, IgA is the dominating Ig in all external secretions of the body. IgM consists of five subunits, similar to monomeric IgA, which are linked together in a circular mode by disulphide bonds and a J chain; the molecular weight of pentameric IgM is approximately 900 kDa. The concentration of the various bovine Igs in serum and in lacteal secretions varies according to the breed, age, health status, and stage of lactation of the animal. In colostrum, Igs make up 70±80 % of the total protein content, whereas in mature milk, immunoglobulins account for only 1±2 % of the protein. The Igs are produced by β-lymphocytes. All Igs exhibit one or more effector function in addition to antigen binding. Whereas one part of an antibody (Fab) binds to antigen, other parts (mostly the Fc region) interact with other elements. In effect, antibodies function as flexible adaptors linking various parts of the immune system. The immunological function mediated by the Igs depends on the Ig class. Sero conversion of IgG to IgA is

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possible in humans. Secretory IgA is associated with beneficial effects on mucosal tissues (gastrointestinal tract and respiratory tract) after immune fatigue induced by exercise. IgG antibodies have other functions such as complement-mediated immunity and bacterial/viral phagocytosis. Lactoferrin Lactoferrin is an iron binding, globular protein found in abundance in human milk. Its molecular weight is 77 kD. Lactoferrin is found in leukocytes and various other body fluids. The principal role of lactoferrin is defense against bacterial pathogens and viruses. Recently, the role of lactoferrin is recognized in immune modulation. Lactoferrin causes significant induction of anti-inflammatory cytokines such as IL-4 and Il-10 and significant reduction in pro-inflammatory cytokines such as IL-1b and TNF-α. This along with intracellular antioxidant activity is associated with beneficial effect in exercise induced immune fatigue. Sialic acid Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. Sialic acids are found widely distributed in animal tissues and to a lesser extent in other species ranging from plants and fungi to yeasts and bacteria, mostly in glycoproteins and gangliosides. The amino group generally has either an acetyl or glycolyl group but other modifications have been described. The hydroxyl substituents may vary considerably: acetyl, lactyl, methyl, sulfate, and phosphate groups have been found. The role of sialic acid is important in viral inactivation, cognitive function and immune activation.

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Proline Rich Polypeptides Proline rich peptides are found in colostrum in abundance. They are a group of peptides with a molecular weight in the range 16,000 to 26,000 Daltons. They are called proline rich because the amount of proline is greater than the amount of any other single amino acid. These peptides are associated with immune balancing effect through their effect thymus gland (T lymphocytes). Research has demonstrated that beyond cognitive function by this neuropeptide family, they have a role in balancing the immune system. When the immune system is depressed, proline peptides upregulate the immune cascade. The inflammatory immune cascade (as in exercise induced immune imbalance) is reversed to bring back proper immune balance. Insulin like Growth Factor (IGF-1) Insulin like growth factor1 protein is a 7649 dalton protein containing 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 is produced primarily by the liver as an endocrine hormone as well as in target tissues in a paracrine/autocrine fashion. Production is stimulated by growth hormones and can be retarded by poor nutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signaling pathway post GH receptor. IGF-1 is beneficially associated with growth and muscle building. Beyond body building and metabolic growth, IGF is also associated with immune modulation. IGF activates weak immune system to more active state. Role of IGF may be important in immunonutrition where exercise or other stress events tend to depress immune system.

Transforming Growth Factor-β (TGF- β) The TGF-β family is part of a family of proteins known as the transforming growth factor beta superfamily, which

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includes inhibins, activin and bone morphogenetic protein. The peptide structures of the three members of the TGF-β family are highly similar. They are all encoded as large protein precursors; TGF-β1 contains 390 amino acids and TGF-β2 and TGF-β3 each contain 412 amino acids. They each have an N-terminal signal peptide of 20-30 amino acids that they require for secretion from a cell, a pro-region (called latency associated peptide or LAP), and a 112-114 amino acid C-terminal region that becomes the mature TGF-β molecule following its release from the pro-region by proteolytic cleavage. The mature TGF-β protein dimerizes to produce a 25 KDa active molecule with many conserved structural motifs. TGF-β has nine cysteine residues that are conserved among its family; eight form disulfide bonds within the molecule to create a cysteine knot structure characteristic of the TGF-β superfamily while the ninth cysteine forms a bond with the ninth cysteine of another TGF-β molecule to produce the dimer. Many other conserved residues in TGF-β are thought to form secondary structures through hydrophobic interactions. The region between the fifth and sixth conserved cysteines houses the most divergent area of TGF-β molecules that is exposed at the surface of the molecule and is implicated in receptor binding and specificity of TGF-β. The role of TGF- β is apparent in immune modulation. TGF- β upregulates mucosal secretion of immunoglobulin from blood plasma in what is known as mucosal immunity generation. TGF-B regulates both arms of immunity and its role is most pronounced in B cell activation and reversing inflammatory cascade (leading to anti-inflammatory outcomes) to provide health benefits. Athletic stress or disease related stress usually results into inflammatory reaction cascade and TGF- β could be useful in mitigating such stress.

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