UNIVERSITY PEDs Human Growth Hormone Lesson Overview What is GH/IGF-1 Role and Mechanism of Action Regulation of GH/IGF-1 Axis GH/IGF-1 effect on hypertrophy Why we retain fluid on HGH? Gender Differences in HGH usage and role of estrogen GH Indirect Actions AAS and HGH synergy Is there a ceiling dosage for HGH? Why Autocrine GH/IGF-1 is Important How should we time HGH? What is the effect of HGH on endocrine production? Does HGH effect Insulin Resistance? Does HGH effect the Thyroid? Is there a maximum dosage for fat loss? Hypertrophy Dosing Recommendations Fat loss Dosing Recommendations GH/IGF-1 Main Purpose How Does it Carry out this Purpose? GH is priming the body for growth by making energy substrate available, Growth is energy costly How Does it Carry out this Purpose? IGF-1 is taking the energy substrate made available by GH and using it for growth and repair IGF-1 Carries out most growth promoting aspects Regulation of GH/IGF-1 Axis GH on Hypertrophy Numerous trials of exogenous GH administration in healthy subjects show no change in muscle protein synthesis or direct hypertrophy outcomes “Effect of growth hormone and resistance exercise on muscle growth in young men”( Yarasheski 1992) Eighteen 21-34-year-old men, 12-week resistance training, 1.5g/kg protein /day; one group placebo, one group GH 0.04mg/kg days per week post workout Plasma insulin and glucose not effected by GH After days treatment water drop Serum GH peaked 2.5hrs post injection “The combination of resistance training and GH administration is no more effective in increasing muscle size and strength and the rate of muscle protein synthesis than resistance training without GH.” Why the Water Retention? ”Effects of growth hormone on renal tubular handling of sodium in healthy humans” (Hansen 2001) day trial, 6IU GH vs control vs GH +400mg Ibuprofen per day GH Indirect Effects on Muscle Growth • Potent stimulator of collagen synthesis in tendons and skeletal muscle, via autocrine IGF-1 mediated fibroblast stimulation Positive application in athlete longevity • Increased decorin gene expression Decorin is protein in skeletal muscle main role is growth and repair • Cell cultures demonstrate GH promote satellite cell proliferation and differentiation into myofibers and provide increase myonuclei Again, not demonstrated in humans • AAS increase satellite cell numbers, providing more raw material for GH to take action on, this is key So, GH alone has minimal impact on hypertrophy does combined AAS usage change this? AAS + GH Synergy “Growth Hormone and Sex Steroid Administration in Healthy Aged Women and Men”( Blackman 2002) 26 week Trial 57 women and 74 men 65-88 yrs old Men: 0.03-0.02mg/kg GH 3x per week + test E 200mg/wk Women: 0.03-0.02mg/kg GH 3x per week + estradiol 100mcg/d + medroxyprogesterone acetate 10mg/day PO Continue normal activity Localized (Autocrine) IGF-1 Levels Only pulsatile GH administration, and not continuous infusion, can maximally stimulate IGF-1 mRNA expression in skeletal muscle (Frost) Pulsatile administration may also lead to comparable, or even decreased, serum systemic IGF-1 levels (Bick) For hypertrophy, peaking GH and getting it back to a baseline level with multiple injections seems ideal There is also a desensitized refractory period within the JAK/STAT5 for ~5hours post GH administration where further administration does not cause same IGF-1 Response (Frost) Insulin can resensitize the JAK/STAT5 pathway to GH A meal between GH administration with an insulin increase would accomplish this GH Timing Three 4-week study periods in random order receiving 1) daily sc injections of IU GH given in the evening (at 2000 h), 2) daily sc injections of IU GH given in the morning (at 0800 h), or 3) no GH (Jorgensen) GH in daytime gave higher serum glucose and insulin levels, while PM administration normalized carbohydrate and lipid metabolism GH bioavailability was further enhanced in PM administration GH and Endocrine GH Suppression 18-month trial HIV patient's GH withdrawal effects ~0.018IU/kg/day (Lo 2010) Single administration of 2IU GH and serum GH levels hours later at onset of sleep (Mendelson 1983) GH and Insulin Resistance “Effects of Growth Hormone on Glucose Metabolism and Insulin Resistance In Human” (Kim 2017) review paper High dose GH usage >0.01mg/kg/day increase fasting glucose and insulin levels and increased insulin resistance, A1c remained relatively unchanged Low dose GH usage post training>Am>pre training) Have a carbohydrate-based meal between dosing for GH/IGF-1 axis resensitization Limit AI, SERM, and thyroid hormone usage 10 Local IM injections can be considered for lagging body parts 11 There is no need for cycling on and off, lowering GH to physiological norm (2-3IU) during cruise periods would be advised for decreased systemic stress and restoring insulin sensitivity 12 Add to anabolic stack early within career to maximize all hypertrophy pathways and enhance current AAS usage, minimal 2IU as starting point Sample GH Layout Meal 1- hour pre meal 1.5-2.0 GH with meal Meal Meal Train Immediate post training 1.5-2.0 GH Meal (post meal) Meal Meal 1.5-2IU pre bedtime GH and Fat loss GH Maximum Rate of Lipolysis? Dose-dependent increase in FFA mobilization from no rHGH to 0.001mg/kg to 0.003mg/kg, no further increase with 0.006mg/kg This would be close to 1.2-1.5IU/100kg GH administered via IV (Hansen 2002) FFA mobilization peak around 150-160min mark Fat Loss Synergies GH increase hormone sensitive lipase, decreases lipoprotein lipase, increased catecholamine sensitivity AAS increase beta adrenergic receptor expression and direct action on the beta receptors Ensure optimal thyroid levels for metabolic rate and beta receptor expression Utilizing a beta-adrenergic receptor agonist like clenbuterol would maximize fat mobilization ability Maximizing GH for Fat Loss GH Dosage fasting for greatest fat loss effect, food does NOT completely blunt effect Dosage of 1.5IU/100kg body weight Perform low to moderate intensity fasted cardio, just water Second GH dosage could be done pre bedtime If choosing between AM or PM, I would choose PM for the enhanced bioavailability Utilize supraphysiological AAS with aromatizing compounds Optimize thyroid function if needed Clenbuterol for enhanced effect Pre-contest drop GH weeks prior to show for drop in water retention 10 For maximizing muscle retention apply recommendation from GH for hypertrophy, dosing can go as high as 6-8IU References Hansen TK, Møller J, Thomsen K, Frandsen E, Dall R, Jørgensen JO, Christiansen JS Effects of growth hormone on renal tubular handling of sodium in healthy humans Am J Physiol Endocrinol Metab 2001 Dec;281(6):E1326-32 doi: 10.1152/ajpendo.2001.281.6.E1326 PMID: 11701449 Ho KY, Weissberger AJ, Stuart MC, Day RO, Lazarus L The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects Clin Endocrinol (Oxf) 1989 Apr;30(4):33545 doi: 10.1111/j.1365-2265.1989.tb00431.x PMID: 2598470 Kimberly T Brill, Arthur L Weltman, Angela Gentili, James T Patrie, David A Fryburg, John B Hanks, Randall J Urban, Johannes D Veldhuis, Single and Combined Effects of Growth Hormone and Testosterone Administration on Measures of Body Composition, Physical Performance, Mood, Sexual Function, Bone Turnover, and Muscle Gene Expression in Healthy Older Men, The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 12, December 2002, Pages 5649–5657, https://doi.org/10.1210/jc.2002020098 Hansen TK, Jørgensen JO, Christiansen JS Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age J Clin Endocrinol Metab 2002 May;87(5):2185-93 doi: 10.1210/jcem.87.5.8473 PMID: 11994362 Meinhardt U, Nelson AE, Hansen JL, Birzniece V, Clifford D, Leung KC, Graham K, Ho KK The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial Ann Intern Med 2010 May 4;152(9):568-77 doi: 10.7326/0003-4819-152-9-201005040-00007 PMID: 20439575 Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR Systematic review: the effects of growth hormone on athletic performance Ann Intern Med 2008 May 20;148(10):747-58 doi: 10.7326/0003-4819-148-10-200805200-00215 Epub 2008 Mar 17 PMID: 18347346 Monroy Guízar EA, García Benavides L, Ambriz Plascencia AR, Pascoe González S, Totsuka Sutto SE, Cardona Muñoz EG, Méndez-Del Villar M Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial J Med Food 2018 May;21(5):521-526 doi: 10.1089/jmf.2017.0056 Epub 2018 Jan 22 PMID: 29356576 Troels Krarup Hansen, Claus Højbjerg Gravholt, Hans Ørskov, Michael Højby Rasmussen, Jens Sandahl Christiansen, Jens Otto L Jørgensen, Dose Dependency of the Pharmacokinetics and Acute Lipolytic Actions of Growth Hormone, The Journal of Clinical Endocrinology & Metabolism, Volume 87, Issue 10, October 2002, Pages 4691–4698, https://doi.org/10.1210/jc.2002-020563 References LIBBIE RUSSO, WAYNE V MOORE, A Comparison of Subcutaneous and Intramuscular Administration of Human Growth Hormone in the Therapy of Growth Hormone Deficiency, The Journal of Clinical Endocrinology & Metabolism, Volume 55, Issue 5, November 1982, Pages 1003– 1006, https://doi.org/10.1210/jcem-55-5-1003 Yarasheski KE, Zachwieja JJ, Campbell JA, Bier DM Effect of growth hormone and resistance exercise on muscle growth and strength in older men Am J Physiol 1995 Feb;268(2 Pt 1):E268-76 doi: 10.1152/ajpendo.1995.268.2.E268 PMID: 7864103 Karila T, Koistinen H, Seppälä M, Koistinen R, Seppälä T Growth hormone induced increase in serum IGFBP-3 level is reversed by anabolic steroids in substance abusing power athletes Clin Endocrinol (Oxf) 1998 Oct;49(4):459-63 doi: 10.1046/j.1365-2265.1998.00556.x PMID: 9876343 Aguirre, Gabriel & Gonzalez-Guerra, Jose-Luis & Espinosa, Luis & Castilla-Cortázar Larrea, Inma (2018) Insulin-Like Growth Factor in 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10.6065/apem.2017.22.3.145 Epub 2017 Sep 28 PMID: 29025199; PMCID: PMC5642081 Anderson LJ, Tamayose JM, Garcia JM Use of growth hormone, IGF-I, and insulin for anabolic purpose: Pharmacological basis, methods of detection, and adverse effects Mol Cell Endocrinol 2018 Mar 15;464:65-74 doi: 10.1016/j.mce.2017.06.010 Epub 2017 Jun PMID: 28606865; PMCID: PMC5723243 Books: Llewellyn W Anabolics Jupiter, FL: Molecular Nutrition LLC; 2017 Bond P Book on Steroids: A complete evidence based reference PeterBond.org; 2020 Swerdloff RS, Ng CM Gynecomastia: Etiology, Diagnosis, and Treatment [Updated 2019 Jul 7] In: Feingold KR, Anawalt B, Boyce A, et al., editors Endotext [Internet] South Dartmouth (MA): MDText.com, Inc.; 2000- Available from: https://www.ncbi.nlm.nih.gov/books/NBK279105/