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HGH-UP - 150 caps
Item Code:APN009-01

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Product Description Supplement Facts Recommended Usage Rating

HGHup™

Hybrid Anabolic / Near Hormonal Support Formula


HGHup is the world’s first hANh™ (Hybrid Anabolic / Near Hormonal); which is defined as a product that engages a synchronization of natural and exogenous factors to produce a pronounced anabolic and hormonal response. The distinct advantage of a hANh is that the user is able to obtain maximal physiological benefits comparable to that of fully hormonal products while minimizing potential side effects and disruption of endogenous factors post-usage.

HGHup IS FORMULATED TO SUPPORT:
•Growth hormone and local IGF-1 levels
•Duration/viability of growth hormone pulse mass
•Androgen receptor structure, function, and number
•Natural production of testosterone


MAIN MECHANISMS OF ACTION:

Mucuna Pruriens, Vitamin B6 and L-Dopa: Support Growth Hormone Output and Testosterone Production While Concurrently Decreasing Somatostatin and Prolactin.

• HGHup contains highly concentrated L-Dopa derived from Mucuna Pruriens.  Mucuna Pruriens is an Ayurvedic Herb that has both anti-hypoglycemic and L-Dopa-increasing qualities. (32). L-Dopa has been shown to significantly increase levels of growth hormone in human subjects when administered orally. (1, 2, 3, 33).  

• Oral viability in HGHUP critical for product effectiveness, as growth hormone cannot be absorbed and is rendered ineffective due to the fragility of the ingredients. Several good examples are synthetic growth hormone (see Fig. 1) and growth hormone releasing hormone (GHRH, see Fig. 2).  These compounds cannot be administered orally; because of their fragile amino acid sequence is destroyed by stomach acids. This also holds true with the vast majority of the so-called “GH Boosters” and “Peptides” commonly found in sports nutrition products.

• L-Dopa and Dopamine have also been shown to inhibit prolactin, a hormone that suppresses male testosterone production. Prolactin also has a positive correlation with a second hormone called somatostatin, which decreases the both amount and effectiveness of circulating growth hormone. Therefore, by lowering prolactin (and consequently somatostatin) levels, HGHUP increases both testosterone and GH production; leading to greater recovery and lean body mass (38, 39).

• Vitamin B6 is also included in the formula for HGHUP, as it can also help further lower prolactin levels and increase the night-time peak of GH release pulse, while at the same time increasing the rise in GH associated with exercise by as much as 23% (7).


Huperzine-A:  AChE Inhibition and Mean serum GH by Decreasing Somatostatin

• Huperzine-A is a strong acetylcholine esterase (AChE) inhibitor.  Acetylcholine esterase inhibitors have been shown in numerous scientific studies to inhibit somatostatin via a variety of synergistic biomechanisms; all of which contribute to increased levels of growth hormone (9, 10, 11, 12, 13, 14, 15, 16, 17, 18).

•  Somatostatin is a hormone that exerts effects on anterior pituitary as well as pancreatic, liver and gastrointestinal function (40, 41, 42, 43) .   

•  Somatostatin is of extreme importance because it directly effects growth hormone release and is the major regulating factor in slowing or even stopping growth hormone output.

•  Therefore, by inhibiting somatostatin, overall mean serum GH will increase (41, 42).
•Somatostatin inhibits GH secretion indirectly via antagonizing GHRH secretion (41, 42, 43).


Green Tea Extract, and (-)-epigallocatechin-3-O-gallate (EGCG): Dopa Decarboxylase Inhibition and the AChE-inhibiting Effects of HGHUP

•Dopamine crosses the blood/brain barrier poorly, and cannot exert optimal effects on target receptors unless enough of the compound reaches the brain.  L-Dopa is freely absorbed across this barrier, and when L-dopa crosses the barrier readily, growth hormone levels increase.  (1-6, 32-33)

•L-Dopa is most effective when conversion of L-Dopa to dopamine is mediated by a decarboxylase inhibitor.  A decarboxylase inhibitor is a substrate that inhibits the metabolism of one biological entity into another biological entity  (2, 3, 4, 5, 19, 20, 37).

•A decarboxylase inhibitor is generally administered at the same time as L-Dopa / Mucuna in order to reduce conversion of the L-dopa into dopamine in the periphery.  (-)-epigallocatechin-3-O-gallate (EGCG), which is found in high amounts in the green tea extract used in HGHUP, is a potent decarboxylase inhibitor.  The decarboxylase-inhibiting qualities of EGCG have been documented in several recent studies, in that EGCG seems to prevent L-dopa from converting into dopamine; allowing more significant levels of L-dopa to reach the brain and increase growth hormone levels (1, 2, 3, 4, 5, 37).

•EGCG has also been shown to significantly increase the effects of Huperzine A on acetylcholine esterase inhibition by increasing the transport of Huperzine-A by serum albumin.  This allows for greater amounts of acetylcholine to be present, therefore allowing for greater mean serum growth hormone. Increased serum GH from HGHUP? allows for increased anabolism, better recovery, and increased muscle mass (19, 20).

HGHUP SUPPORTS ANDROGEN RECEPTOR QUANTITY AND DENSITY AND FOR A BETTER BINDING ENVIRONMENT FOR EXISTING ANDROGENS

L-Carnitine-L-Tartrate and Magnesium:  Androgen Receptor Number and Density, and the Creation of a Better Binding Environment

• L-Carnitine L-Tartrate is an amino acid that has been shown to increase the number of androgen receptors in skeletal muscle, creating a better binding environment for testosterone and other androgens by allowing for a greater number of intact receptors available for hormonal interactions. (21-23)

• Magnesium has been shown in more recent studies to inhibit the binding of steroid hormone binding globulin (SHBG) and free testosterone.  SHBG binds free testosterone and allows it to be excreted from the body, without binding the androgen receptor.  Magnesium keeps this from happening by altering the binding affinity of testosterone to SHBG; thereby allowing for increased amounts of free testosterone to remain active in the bloodstream. (24)

• Other human research has shown that supplemental magnesium, when taken along with other ingredients like DHEA and Zinc, can significantly increase free testosterone. (25-27)

• Therefore, HGHUP allows for greater numbers of androgen receptors and a better binding environment for testosterone in skeletal muscle. This is a new breakthrough in sports supplementation as HGHUP creates a better target for circulating free testosterone, allowing for greater binding of testosterone to the extra receptors which leads to increased protein synthesis, better recovery, and increased muscle mass.

HGHUP SUPPORTS TESTOSTERONE

Mucuna Pruriens, Selenium, and Chlorophytum Borivillanum Ethanolic/Sapogenic Extract: Testosterone Levels

• Mucuna Pruriens has been shown in several recent human studies to improve testosterone levels and spermatogenesis in animal studies and humans, via prolactin inhibition. Prolactin, as mentioned earlier, is a hormone that suppresses male testosterone production (30-31, 34-36, 38-39).

• The ethanolic and sapogenic extracts of Chlorophytum Borivaillanum have also been shown in animal studies to increase testosterone, and anecdotal data from products containing this compound also point to increased testosterone and lean body mass for users of this phyto-androgenic compound. However, the mechanism of action of Chlorophytum is poorly understood. (28- 29)


Studies and Clinical Info
1.Hanew, K., Tanaka, A, and Utsumi, A.  Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential administration of GHRH and combined administration of PD and GHRH in Turner’s syndrome. J. Endocrinol. Invest. 1998. Feb.; 21(2): 72-77.
2.Schönberger W, Grimm W, Ziegler R. The effect of nacom (L-dopa and L-carbidopa) on growth hormone secretion in 75 patients with short stature. Eur J Pediatr. 1977 Dec 30;127(1):15-9.
3.Schönberger W, Ziegler R, Brodt B, Grimm W. HGH secretion after oral application of L-dopa and L-carbidopa. Eur J Pediatr. 1976 Jun 8;122(3):195-200.
4.Fevang FO, Stoa RF, Thorsen T, Aarskog D. The Effect of L-dopa with and without decarboxylase inhibitor on growth hormone secretion in children with short stature. Acta Paediatr Scand. 1977 Jan; 66(1):81-84
5.Philippi H, Pohlenz J, Grimm W, Koffler T, Schönberger W. Simultaneous stimulation of growth hormone, adrenocorticotropin, and cortisol with L-dopa, carbidopa, and propranolol in children of short stature. Acta Paediatr, 2000 Apr;89(4):442-446.
6.Gordon M, Markham J, Hartlein JM, Koller JM, Loftin S, Black KJ. Intravenous levodopa administration in humans based on a two-compartment kinetic model. J. Neurosci Methods, 2007 Jan 30:159(2):300-307. Epub 2006 Aug 24
7.Pyridoxine (B6) suppresses the rise in prolactin and increases the rise in growth hormone induced by exercise. 1982 Aug 12;307(7):444-5.
8.Barletta C, Sellini M, Bartoli A, Bigi C, Buzzetti R, Giovannini C Influence of administration of pyridoxine on circadian rhythm of plasma ACTH, cortisol prolactin and somatotropin in normal subjects. Boll Soc Ital Biol Sper. 1984 Feb 28;60(2):273-8
9.Gordon RK, Haigh JR, Garcia GE, Feaster SR, Riel MA, Lenz DE, Aisen PS, Doctor BP. Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman. Chem Biol Interact. 2005 Dec 15;157-158:239-46. Epub 2005 Oct 26.
10.Wang R, Yan H, Tang XC. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006 Jan;27(1):1-26
11. Kelijman M, Frohman LA. The role of the cholinergic pathway in growth hormone feedback. J Clin Endocrinol Metab. 1991 May;72(5):1081-7
12. Liang YQ, Tang XC. Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats. Acta Pharmacol Sin. 2006 Sep;27(9):1127-36
13. Giustina A, Bossoni S, Bodini C, Doga M, Girelli A, Buffoli MG, Schettino M, Wehrenberg WB. The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man. Metabolism. 1991 May;40(5):519-23
14.Friend K, Iranmanesh A, Login IS, Veldhuis JD Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release. Eur J Endocrinol. 1997 Oct;137(4):377-86
15.Dinan TG, O'Keane V, Thakore J. Pyridostigmine induced growth hormone release in mania: focus on the cholinergic/somatostatin system. Clin Endocrinol (Oxf). 1994 Jan;40(1):93-6
16. Thakore JH, Coffey I, Dinan TG. Time dependency of pyridostigmine-induced growth hormone response. J Basic Clin Physiol Pharmacol. 1994 Apr-Jun;5(2):117-2
17.Li YX, Zhang RQ, Li CR, Jiang XH. Pharmacokinetics of huperzine A following oral administration to human volunteers. Eur J Drug Metab Pharmacokinet. 2007 Oct-Dec;32(4):183-7.
18.Haigh JR, Johnston SR, Peppernay A, Mattern PJ, Garcia GE, Doctor BP, Gordon RK, Aisen PS. Protection of red blood cell acetylcholinesterase by oral huperzine A against ex vivo soman exposure: next generation prophylaxis and sequestering of acetylcholinesterase over butyrylcholinesterase. Chem Biol Interact. 2008 Sep 25;175(1-3):380-6.
19. Xiao J, Chen X, Zhang L, Talbot SG, Li GC, Xu M. Investigation of the mechanism of enhanced effect of EGCG on huperzine A's inhibition of acetylcholinesterase activity in rats by a multispectroscopic method.  J Agric Food Chem. 2008 Feb. 13:56(3) 910-915.
20. Zhang L, Cao H, Wen J, Xu M. Green tea polyphenol (-)-epigallocatechin-3-gallate enhances the inhibitory effect of huperzine A on acetylcholinesterase by increasing the affinity with serum albumin.
21. DI MARZIO L. (1) ; MORETTI S. (2) ; D'ALO S. (1) ; ZAZZERONI F. (1) ; MARCELLINI S. (2) ; SMACCHIA C. (3) ; ALESSE E. (1) ; CIFONE M. G. (1) ; DE SIMONE C. (1) ; Acetyl-l-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects : Correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation.
22. Kraemer WJ, Spiering BA, Volek JS, Ratamess NA, Sharman MJ, Rubin MR, French DN, Silvestre R, Hatfield DL, Van Heest JL, Vingren JL, Judelson DA, Deschenes MR, Maresh CM. Androgenic responses to resistance exercise: effects of feeding and L-carnitine. Med Sci Sports Exer., 2006 Jul: 38(7): 1288-96.
23.Kraemer WJ, Volek JS, French DN, Rubin MR, Sharman MJ, Gómez AL, Ratamess NA, Newton RU, Jemiolo B, Craig BW, Häkkinen K. The effects of L-carnitine L-tartrate supplementation on hormonal responses to resistance exercise and recovery. J Strength Cond. Res. 2003 Aug: 17(3): 455-462,
24. André C, Berthelot A, Robert JF, Thomassin M, Guillaume YC. Testimony of the correlation between DHEA and bioavailable testosterone using a biochromatographic concept: effect of two salts. J Pharm Biomed An., 2003 Dec 4: 33(5): 911-21.
25. Excoffon L, Guillaume YC, Woronoff-Lemsi MC, André C. Magnesium effect on testosterone-SHBG association studied by a novel molecular chromatography approach. J Pharm Biomed An. 2009 Feb. 20: 49(2). 175-180.
26.Age-Related Eye Disease Study Research Group (2001). “A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss. Arch Opthalmology. 119(10): 1417.
27. Berdanier, Carolyn D.; Dwyer, Johanna T.; Feldman, Elaine B. (2007). Handbook of Nutrition and Food. Boca Raton, Florida: CRC Press.
28.Thakur M. and Dixit V.K.* EFFECT OF CHLOROPHYTUM BORIVILIANUM ON ANDROGENIC & SEXUAL BEHAVIOR OF MALE RATS Indian Drugs 2006 April 43(4): 300-306
29. Kothari S.K., Safed Musli (Chlorophytum borivilianum) revisited, Journal of Medicinal and Aromatic Plants. 2004, 26, 60-63.
30. Saxena S and Dixit V.K: Role of total alkaloids of Mucuna pruriens Baker in spermatogenesis in male rats, Indian Journal of Natural Products. 1987, 3(2), 3-7.
31. Unnithan A.R. and Tandon V.L: Role of growth hormone in spermatogenesis in male rats. Indian Journal of Experimental Biology. 1982,20,734-737.
32. Modi KP, Patel NM, Goyal RK. Estimation of L-dopa from Mucuna pruriens LINN and formulations containing M. pruriens by HPTLC method Chem Pharm Bull (Tokyo). 2008 Mar: 56(3): 357-359.
33.Tharakan B, Dhanasekaran M, Mize-Berge J, Manyam BV. Anti-Parkinson botanical Mucuna pruriens prevents levodopa induced plasmid and genomic DNA damage.Phytother Res. 2007 Dec;21(12):1124-6.
34.Ahmad MK, Mahdi AA, Shukla KK, Islam N, Jaiswar SP, Ahmad S.
Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men. Fertil Steril. 2008 Sep;90(3):627-35. Epub 2007 Nov 14.
35. Shukla KK, Mahdi AA, Ahmad MK, Shankhwar SN, Rajender S, Jaiswar SP. Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis. Fertil Steril. 2008 Oct 28. [Epub ahead of print]
36.Shukla KK, Mahdi AA, Ahmad MK, Jaiswar SP, Shankwar SN, Tiwari SC .Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men .Evid Based Complement Alternat Med. 2007 Dec 18. [Epub ahead of print
37.Bertoldi M, Gonsalvi M, Voltattorni CB. Green Tea polyphenols: Novel irreversible inhibitors of dopa decarboxylase  Biochem Biophys Res Commun. 2001 Jun 1;284(1):90-3.
38.Vaidya RA, Aloorkar SD, Sheth AR, Pandya SK. Activity of bromoergocryptine, Mucuna pruriens and L-dopa in the control of hyperprolactinaemia. Neurol India. 1978 Dec;26(4):179-82.
39.Vaidya RA, Sheth AR, Aloorkar SD, Rege NR, Bagadia VN, Devi PK, Shah LP. The inhibitory effect of the cowhage plant- mucuna pruriens-and L-dopa on chloropromazine-induced hyperprolactinemia. Neurol India. 1978 Dec;26(4):177-8.
40. Epelbaum J, Guillou JL, Gastambide F, Hoyer D, Duron E, Viollet Somatostatin, Alzheimer's disease and cognition: An old story coming of age? C. Prog Neurobiol. 2009 Jul 10.
41.Nikolaeva AA, Koroleva SV, Ashmarin IP. [Research of interactions in the dopamine-serotonin-somatostatin system promises new outlook in fundamental and practical respects] Nikolaeva AA, Koroleva SV, Ashmarin IP. Eksp Klin Farmakol. 2009 Mar-Apr;72(2):60-4. Review
42. Cordido F, Isidro ML, Nemiña R, Sangiao-Alvarellos S.Ghrelin and growth hormone secretagogues, physiological and pharmacological aspect. Curr Drug Discov Technol. 2009 Mar;6(1):34-42.
43.Strowski MZ, Blake AD. Function and expression of somatostatin receptors of the endocrine pancreas. Mol Cell Endocrinol. 2008 May 14;286(1-2):169-79.
44. Haff, G. Lecture Notes for Graduate Study: Hormonal Parameters Relevant to Training. Appalachian State University, 2000.
45.  Khoo, B. and Grossman, A. Normal Physiology of the Hypothalamus and Anterior Pituitary. St. Bartholomew’s Hospital, West Smithfield, London. Neuroendocrinology, Hypothalamus, and Pituitary. 2007  Ch. 1 Lecture.
46.Various sources. Anecdotal Information concerning the usage of AChE inhibitors with synthetic GH.
47. Applied Nutriceuticals Research. Unpublished alpha testing for new somatotropin-enhancing sports supplement. Charlotte, NC. 2009
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