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A 100% Natural Growth Hormone Secretagogue © 2006 -2013 Millennium Health Centers, Inc. 08-01-2013.

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Presentation on theme: "A 100% Natural Growth Hormone Secretagogue © 2006 -2013 Millennium Health Centers, Inc. 08-01-2013."— Presentation transcript:


2 A 100% Natural Growth Hormone Secretagogue © Millennium Health Centers, Inc

3 Secretropin ® The Logical First Step in GH Therapy. © Millennium Health Centers, Inc.

4 A secretagogue is a substance that causes another substance to be secreted. SRx Simulates GHRF © Millennium Health Centers, Inc.

5 Youthful production of GH and Older Production The number of pulses and the amplitude of hormone production decreases as we get older. © Millennium Health Centers, Inc.


7 Low Dose GH Stimulation vs. High Dose Stimulation Over stimulation of the AP leads to an elevation in the production of Somatostatin with a corresponding decrease in the release of GHRH leading to down regulation in the production of growth hormone. © Millennium Health Centers, Inc. Somatostatin

8 The Threshold Theory of GH Production 1.GH is a central and peripheral trigger of the feed-back loop. i.Down regulation of GHRH-receptors ii.Down regulation of Arcuate Nucleus production of GHRH iii.Up-regulation of Somatostatin (SRIF) from the Paraventricular nucleus of the hypothalamus. 2.IGF-1 is a peripheral trigger of the central feed-back loop. i.Down regulation of GHRH-receptors ii.Down regulation of Arcuate Nucleus production of GHRH iii.Up-regulation of Somatostatin (SRIF) from the Paraventricular nucleus of the hypothalamus. © Millennium Health Centers, Inc.

9 The Threshold Theory of GH Production 1.When GH reaches the individuals threshold for Negative Feedback: i.Somatostatin increases thereby down- regulating GH production and release. 2.When IGF-1 reaches the individuals threshold for Negative Feedback: i.Somatostatin increases thereby down- regulating GHRH and GHRH-r production. © Millennium Health Centers, Inc.

10 Neuroendocrine Control of Growth Hormone Secretion. PHYSIOLOGICAL REVIEWS Vol. 79, No. 2, April Eugenio E. Muller, Vittorio Locatelli, Daniela Cocchi, Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Milan; and Department of Biomedical and Biotechnology Sciences, University of Brescia, Brescia, Italy © Millennium Health Centers, Inc.

11 Repeated stimulation of pituitary cell cultures with GH-releasing hormone results in diminished responsiveness, a phenomenon referred to as homologous desensitization. One component of GHRH-induced desensitization is a reduction in GHRH-binding sites, which is reflected by the decreased ability of GHRH to stimulate a rise in intracellular cAMP. © Millennium Health Centers, Inc. Homologous Down-Regulation of Growth Hormone- Releasing Hormone Receptor mRNA Levels* Endocrinology 138: 1058–1065, 1997 Grazia Aleppo, Stanley F. MOSKAL II, Paula A. De Grandis, Rhonda D. Kineman,Lawrence A. Frohman, Department of Medicine, Section of Endocrinology and Metabolism, University of Illinois at Chicago, Chicago, Illinois 60612


13 © 2010 Millennium Health Centers, Inc. Many Secretagogues GHRFs GHRH GH DHEA Dopamine Non-Peptides Peptides Arginine Amino Acids Vitamin Vitamin D3 Melatonin © Millennium Health Centers, Inc.

14 Growth hormone secretagogues: recent advances and applications. DRUG DISCOVERY TODAY 1999 Nov;4(11): Ankersen Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Malov, Denmark. The discovery of a new class of compounds that stimulate the release of growth hormone (GH) in a manner distinctly different from growth hormone- releasing hormone (GHRH) is advancing the understanding of the mechanisms that control GH secretion. These compounds, the GH secretagogues, act at both pituitary and hypothalamic levels, and even elicit effects in the CNS and peripheral systems. © Millennium Health Centers, Inc.

15 Growth Hormone-Releasing Peptide (GHRP). Cell Mol Life Sci. 1998; 54(12): Bowers CY. Tulane University Medical School, New Orleans, Louisiana 70112, USA. Growth Hormone-Releasing Peptides and Non-Peptides are a chemical class of Growth Hormone secretagogues with a chemistry that ranges from small synthetic peptides to peptidomimetics (natural) substances. They have no structural homology with (GHRH) but act via specific receptors, which are present at both the pituitary and hypothalamic levels. © Millennium Health Centers, Inc.

16 Specific receptors for synthetic GH Secretagogues in the human brain and pituitary gland. Journal of Endocrinology (1998) 157, 99–106. G Muccioli, Et Al. Department of Anatomy, Pharmacology and Forensic Medicine, Department of Biomedical Sciences and Human Oncology, Department of Internal Medicine, University of Turin, Turin, Italy, Pharmacia and Upjohn, Stockholm, Sweden, Europeptides, Argenteuil, France, and Faculty of Pharmacy, University of Montreal, Montreal, Canada. A number of research centers have identified specific receptors in the human brain and pituitary gland that are unique for sGHS. These compounds are believed to be the synthetic counterpart of an endogenous GH secretagogue involved in the neuroendocrine control of GH secretion ( Ghrelin). © Millennium Health Centers, Inc.

17 Endocrine and non-endocrine activities of growth hormone secretagogues in humans. Hormone Research ; 51 Suppl 3:9-15. Ghigo E; Arvat E; Broglio F; Giordano R; Gianotti L; Muccioli G; Papotti M; Graziani A; Bisi G; Deghenghi R; Camanni F Department of Internal Medicine, University of Turin, Italy. Furthermore, these secretagogues (s-GHS) have been found to possess strong, dose-dependent and reproducible GH releasing effects. © Millennium Health Centers, Inc.

18 DHEA in vitro, directly or indirectly through conversion into metabolites, is able to modulate the hormonal response of the pituitary to hypothalamic regulators. DHEA enhances pituitary prolactin release and induces GH secretion. These effects could help explain some of the beneficial side effects observed in patients on prolonged DHEA treatments, and therefore, should be taken into account when considering its use. Dehydroepiandrosterone modulates GHRH, Somatostatin, and angiotensin II action at the pituitary level. Journal of Endocrinology (2005) 185, 165–172C Suárez, J Vela, I García-Tornadú and D Becu-Villalobos Instituto de Biología y Medicina Experimental, CONICET, V, Obligado 2490, Buenos Aires 1428, Argentina. © Millennium Health Centers, Inc.

19 DHEA replacement in female patients lead to a 20% reduction in the dose of GH for a constant serum IGF-I. This was maintained for 12 months and there was a significant fall in serum IGF-I two months after withdrawal of DHEA. Therefore, take at night and not in the morning to enhance GH production. Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement. Clin Endocrinol (Oxf). 2006; 65(5):673-80,Brooke AM; Centre for Clinical Endocrinology, William Harvey Research Institute, St.Bartholomew's Hospital, QMUL, London, UK. © Millennium Health Centers, Inc.

20 The Dopamine receptor (DRD2) plays a major role in growth hormone (GH) secretion. Binding to D2R increases the production and release of Growth Hormone. Allelic variations of the D2 dopamine receptor gene in children with idiopathic short stature. J Hum Genet. 1999;44(1):26-9. Miyake H, Nagashima K, Onigata K, Nagashima T, Takano Y, Morikawa A.Department of Pediatrics, Gunma University School of Medicine, Japan. © Millennium Health Centers, Inc.

21 The effect of L-dopa, on GH secretion was studied in a group of patients with Parkinson's disease undergoing treatment with the drug. The rise in plasma GH persisted for 120 minutes after the administration of the drug. ( The L-dopa-induced rise in plasma GH could not be blocked by either oral or intravenous glucose administration. ) Stimulation of Human-Growth-Hormone Secretion by L- Dopa. N Engl J Med 1970; 283: Dec. 24, A. E. Boyd, III, M.D., Harold E. Lebovitz, M.D., and John B. Pfeiffer, M.D. From the divisions of Endocrinology and Neurology, Department of Medicine, Duke University Medical Center. © Millennium Health Centers, Inc.

22 Use of amino acids as growth hormone-releasing agents by athletes. Nutrition Jul-Aug;18(7-8): Chromiak JA, Antonio J.Department of Health, Physical Education, Recreation and Sport, Mississippi State University, PO Box 6186, Mississippi State, MS , USA. Specific amino acids, such as arginine, lysine and ornithine, have been shown to stimulate GH release when infused intravenously or administered orally. Although parenteral administration consistently leads to increased circulating GH concentration, oral doses that are great enough to induce significant GH release are also likely to cause GI discomfort and diarrhea. © Millennium Health Centers, Inc.

23 Product(s)Response Arginine250mg/kg/day 60% increase in GH Ornithine400% increase in baseline IV Ornithine500% increase of GH over baseline. Alpha-Keto Glutarate Significant increase in GH in TBI patients. Glutamine2 grams increase GH GABA5 grams increase GH Glycine6.7grams increased GH % © Millennium Health Centers, Inc.

24 Arginine stimulates growth hormone secretion by suppressing endogenous Somatostatin secretion. Journal of Clinical Endocrinology & Metabolism, Vol 67, , J Alba-Roth, OA Muller, J Schopohl, K von Werder Medizinische Klinik Innenstadt, University of Munich, West Germany. Arginine administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arginine alone. This indicated that the stimulatory effects of Arginine are mediated by suppression of endogenous Somatostatin secretion (SRIF). © Millennium Health Centers, Inc.

25 Vitamin D and growth hormone regulate growth hormone/insulin-like growth factor (GH–IGF) axis gene expression in human fetal epiphyseal chondrocytes. Growth Hormone & IGF Research Volume 19, Issue 3, June 2009, Pages 232–237. M. Fernández-Cancio, Vitamin D, dose-dependently, stimulated GHR, IGF-I, and IGFBP-3 expression. 24 © Millennium Health Centers, Inc.

26 . Veldhuis JD, Keenan DM, Bowers CY. Am J Physiol Regul Integr Comp Physiol Oct;293(4):R Epub 2007 Aug. Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Unit, Mayo Clinic, Rochester, MN55905, USA. Peripheral estrogen receptor alpha selectively modulates the waveform of GH secretory bursts in healthy women. Veldhuis JD, Keenan DM, Bowers CY. Am J Physiol Regul Integr Comp Physiol Oct;293(4):R Epub 2007 Aug. Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Unit, Mayo Clinic, Rochester, MN55905, USA. Estradiol drives GH secretion via estrogen receptors (ER-α) located in the hypothalamus and pituitary gland. © Millennium Health Centers, Inc.

27 Supraphysiological testosterone concentrations increase GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone up-regulation. Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy. Eur J Endocrinol. 2005; 153(4): Veldhuis JD; et. Al,. Dept of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905, USA. © Millennium Health Centers, Inc.

28 ItemIncreaseDecrease Melatonin + Estradiol + Dopamine + DHEA + Testosterone + Tamoxifen -- Sermorelin + Vitamin D + Alcohol -- FATS - Carbohydrates - Obesity -- © Millennium Health Centers, Inc.

29 Summary - The research literature supports the ability of atypical substances to increase the production and release of Growth Hormone through a number of receptor pathways. - These substances have been found to be amino acids, non-peptides, peptides, synthetic peptides, DHEA, Dopamine, which enhance the activity level of Somatotropes increasing production of GH. - To work they must be introduced into a homeostatic hormonal environment. © Millennium Health Centers, Inc.

30 © 2010 Millennium Health Centers, Inc.

31 Dopamine DHEA Arginine Amino Acids Melatonin Peptides Vitamin D HCl © Millennium Health Centers, Inc. Protection from Acid Destruction.

32 Nano-Liposomes filled with SRx © Millennium Health Centers, Inc. Nano-spheres or emulsions to diffuse into the blood. Size does matter!

33 Liposomal delivery systems are effective vehicles to incorporate active agents into compartmentalized structures for the delivery of pharmaceutical, cosmetic, food and nutritional products. A major benefit of liposomal delivery systems is that they allow for spatial and temporal distribution of a drug in the body, reducing unwanted toxic side effects and increasing efficiency of treatment. © Millennium Health Centers, Inc. Analytical methods for the control of liposomal delivery systems. Revue TrAC. Trends in analytical chemistry, 2006, vol. 25, pp Gomez-Hen. ; Fernandez- Romero J. M.

34 © Millennium Health Centers, Inc. 1 gram of orally ingested Vitamin C had a 19% absorption while 1 gram in a Nanoliposomal based product had a 97% delivery.

35 The original clinical testing of Secretropin was performed in The original formula delivered by nanoliposomes was found to increase the production of GH based upon a measurable increase in IGF-1. At that time, IGF-1 was the only test used to monitor responsiveness to the product. Today IGFBP-3 has been shown to be logarithmically proportional to GH production. © Millennium Health Centers, Inc.

36 © 2010 Millennium Health Centers, Inc. © Millennium Health Centers, Inc.

37 The October 2006 Study Sequence The March 2008 Report. The March 2009 Report and pending March Goal to have 100 patients followed for 6 – 12 months with labs drawn initially and monthly thereafter. © Millennium Health Centers, Inc.

38 Initial 1 month 3 months 6 months 62.9% 78.6% 98.7% © Millennium Health Centers, Inc.

39 MK. 50 y/o Female 233% Stopped SRx due to increased muscularity. Levels dropped. Result6/21/20073/22/20071/09/2007 IGF IGFBP © Millennium Health Centers, Inc.

40 JC, 47 y/o Male. 238% Increase TBI case, 5 TBI, 3 LOC, one hospitalization. ResultRange9/06/20074/04/200712/26/2006 IGF > 200 ng/ml IGFBP-35693> 4000 ng/ml © Millennium Health Centers, Inc.

41 NJ: 34 y/o Male 199.2% Cryptorchism. ResultRange1/10/200810/30/20072/20/2007 IGF > 200 ng/ml IGFBP-33824> 4000 ng/ml © Millennium Health Centers, Inc.

42 Generally speaking: High initial IGF-1/BP-3 are more prone to shut down then those with initial low IGF-1/BP-3 levels. Continuous 4 - sprays © Millennium Health Centers, Inc IGF-1 Results at approx. 1 month intervals (3mos) 6 5

43 Initial Treatment Secretropin (SRx) 1mo Laboratory No Change/Decrease Increase Continue Adjust Dosing 3mos Failed 3mos © Millennium Health Centers, Inc.

44 ProgramSecretropinGrowth Hormone Initial Protocol4 sprays to startNone Combined protocol4 sprays, adjust0.1mg – 0.3mg Established GH Use4 sprays to start.Reduce GH based upon response. Post-GH Shutdown4 Sprays, adjust.None 1.In a GH deficient or insufficient patient start SRx and adjust dose for maximal response. Monitor over 3 months. 2.Starting a new patient on both GH and SRx allows for the use of a lower dose of GH with comparable results in both IGF-1 and BP-3 levels. 3.In a patient already on GH, add SRx and adjust for maximal IGF-1/BP-3 levels. You should have a spike in GH production within 3 months. 4.Patients who have been on GH for 6 months or more should start SRx having both IGF-1 and GH monitored. Before starting SRx, wait 4 weeks before taking initial IGF-1 and BP-3 levels for baseline. Monitor Q3months. © Millennium Health Centers, Inc.


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