Some interesting reads on if hgh is worth it by knowledgeable people

[wsw16]

Here are some reads that people may find interesting on the effects of hgh, if it's worth it, is it good for hypertrophy etc

These were posted by an ifbb pro on facebook who sought the opinion of some health experts who are also very knowledgeable on bodybuilding to comment on hgh and it's effects. You may not agree with everything they say (I definitely don't) but they are interesting reads none the less and very well referenced.

Would be good to get Mands thoughts and Dr Jim etc

One of the most comprehensive arguments AGAINST using HGH and Bodybuilding thanks to Bradley Clarke.

Respect to Bradley for using a writing style that allows your average gym rat to understand too.

Brads qualifications include:
Master of Human Factors Engineering and Health Science
DipAppSci;AdvDipEnv;AdvDipBus;GradCertForensInv;ME SH;MA; MSIA;MHFESA
Scientific Investigator and Performance Chemist
5thprinciple.info

What’s wrong with Growth Hormone?
Today I am going to explain why I think growth hormone may well represent everything that I think is wrong with bodybuilding today.
It would be fair to say that the physiques of the 1970s had better symmetry than many of today’s larger frames and might have been easier to achieve for a couple of reasons. It appears to me that as time has gone on from the 1990s, midsection thickness has become the mainstay of today’s shape. This may be, in most part, due to growth hormone supplementation.

I am not talking about growth hormone secretion within the athletes own body but the supraphysiological use of pharmaceutical grade material which is targeting every tissue in the body but skeletal muscle. This means that rather than having a 28 inch waist like Flex Wheeler did, some body builders are on stage with what easily appear to 40 inch waists. [1] A few pros have managed to rein it in but many have not.

We must begin with some overarching comments in that growth hormone is a controlled poison for which both Customs and the various state police forces take umbrage at the importation, possession and use. Because of the high desirability of growth hormone, the chance of purchasing fake material in plain vials or counterfeit labelled materials in vials, ampules and boxes is also high. Coupled with the fact that growth hormone is expensive, grows tissue other than skeletal muscle thus thickens your waist means that you need to significantly grow your upper body to increase the appearance of clavicle width. This might add years you your journey.

So what does growth hormone do and at what dose? I’m happy to be wrong but don’t argue with me brining anecdote. What I am about to report is peer reviewed studies controlled for variables and the compounds used were real and known. I might also say that all of these research papers are written by people smarter than me and some of the papers have more than 10 authors who are all smarter than me.

Firstly, growth hormone is not antiaging. That’s become a massive scam and to be blunt, growth hormone is both disease promoting and pro-aging. Growth hormone promotes proliferation and mitosis of various tissues including cancer lines. It upregulates cell turnover which in effect is like photocopying copies of photocopies. Rather than cells spending more time in rest and repair phase of the cell cycle, they are quickly pushed through the cycle proliferating errors.
Growth hormone increases circulating IGF-1 which in most populations is not desirable. While IGF-1 is a potent anabolic and the only means by which growth hormone has any influence over skeletal muscle, oestrogen rather has the effect of increasing IGF-1 in contracting muscle. That is where it is desirable, not in lung and brain tissue. In fact, mice with diminished capacity to produce and receive growth hormone live 30 to 70% longer than their full GH cousins. [2-7]
Growth hormone increases insulin resistance which may have long lasting effects beyond the gym and into middle life. [8-10] While normal growth hormone levels are desirable to maintain generalised health, the reduction in insulin sensitivity brought about by high levels of growth hormone needs to be considered in order to reduce the likelihood of accreting visceral body fat after administration has ceased. The effectiveness of co-administrated insulin is affected as is the uptake of amino acids which use the insulin system for cellular transport. This is also disease promoting including fatty liver disease, heart disease, tissue degradation and sexual health. [11-14]
Growth hormone administration increases the size of smooth muscle including the viscera and vascular system. This is one of my main contentions, that thicker midsections mean that greater upper body volume is required to maintain symmetry. There is not a lot of research into high dose growth hormone administration on smooth muscle but we can start with the symptoms of acromegaly (excess GH production and secretion). In smooth muscle tissue such as the heart in which constant exposure to high levels of growth hormone occurs, a heart may weigh as much as 1000g. [15] In normal persons a large heart may be 300g. Liver cells are a target tissue for growth hormone as is cells of the stomach and upper gastrointestinal tract as well as bone tissue such as feet, hands and jaw. [16,17]

One beneficial targets for growth hormone is fibroblasts which build connective tissue such as tendons and cartilage. I have no issue there although fibroblast growth factor and procollagen 1 are better growth factors in that regard.
Moreover, growth hormone administration has been associated with Creutzfeldt-Jakob disease from human sources as recent as 20 years ago. [18-21] There is no evidence that black market hGH has not come from cadavers.

Now there is always a trade-off between health and performance. The consumption of milk protein is associated with breast cancer and a diet high in leucine is a risk factor for melanoma. The benefit is growth of skeletal muscle so the risk to benefit ratio is balanced toward using the supplements. So we would want growth hormone to build muscle in order to offset the negative effects, right?

Let’s look at a range of studies in athletes and normal subjects using both growth hormone in isolation and with steroids. I have put an approximate value of each program based on period of trial and volume used, at $10 per IU.
A study of 16 untrained men, aged 18 to 28 years, administered growth hormone at 0.56 IU/kg/week (say 6.4iu per day at 80kg) or placebo over 12 weeks of heavy resistance training. [22] After 12 weeks there was a more pronounced increase in free fatty mass and total body water in the growth hormone group compared to placebo, but there was no difference in muscle strength or limb circumference. The quadriceps muscle protein synthesis rate showed no difference between the groups. $5376
Seven trained weight-lifters with a mean age of 23 years were administered 0.56 IU/kg/week (same as the previous trial) during 14 days of heavy training. There was no increase in fractional rate of muscle protein synthesis and no decrease in whole body protein breakdown after 2 weeks. [23] $896
In a study which used 22 male power athletes, aged 18 to 48, growth hormone was administered at 0.63 IU/kg/week (say 7.2iu for 80kg) or placebo during six weeks exercise. The researchers found no difference in maximal voluntary strength of biceps or quadriceps muscles. There was no change in body weight or body fat decrease between the groups. [24] $3024

In a study looking at elderly men over 14 weeks of initial progressive resistance training, followed by 0.28 IU/kg/week (say 3.2iu) of growth hormone or placebo, administered over 10 weeks. Biopsy of the vastus lateralis muscles was performed at baseline and after 14 and 24 weeks. There was no change in muscle strength, morphology or muscle GH/IGF-I mRNA expression between the growth hormone and placebo groups. [25] $2240

In one study of male sprinters (63) which combined 250mg of testosterone per week with 6iu of growth hormone per day (funded by WADA), sprint capacity increased however other parameters such as plyometric strength did not. Further, the increase in lean mass associated with growth hormone was attributed to water retention. Increased capacity to sprint decreased to baseline after a six week wash out period. [26] $2520 (GH alone)

In a 28 day study of 30 young men and women, receiving 16iu per day at the highest dose, found no improvement in power output or oxygen uptake.[27] $4480 for the highest dosed group.
In a study of seven young men receiving 7.5iu growth hormone per day or placebo, over 4 days found that there was a greater mobilisation of fat stores but no greater oxidation during exercise. [28] $300

In another study looking at 31 older men, growth hormone administration at 1.8iu per day over 12 weeks ($1512) found no change in quadriceps power or muscle fibre number. What the study did show however is that in the placebo group the fibre type 2a moved toward 2x characteristics where in the growth hormone group 2x moved toward type 2a characteristics. [29]

In a study which looked at endogenous hormone levels in trained athletes, neither growth hormone nor testosterone secretion increase led to greater hypertrophy or strength. While this was not a study on supraphysiological doses, it does add an interesting dimension to the argument. [30]

I conclude by saying that the pro-aging effects of growth hormone combined with increases in tissue other than skeletal muscle are not worth the investment even if you consider the beneficial albeit transient results seen in the WADA funded study. The health concerns and increased risk of side effects seen in the Berggren et al study at doses greater than 16iu per day (at say the 28 days) do not correlate with any potential gains even accounting for the addition of other anabolic augmentation usually undertaken by bodybuilders. That study saw an investment of $4480 over 28 days which could be equivalent to an additional dietary intake of 8kg of steak per day if the investment was redirected. Red meat is anabolic in its own right (and apparently manly). [31-34]

1 Krasniewicz, L., & Blitz, M. (2006). Arnold Schwarzenegger: a biography. Greenwood Publishing Group.
2 Vance, M. L. (2003). Can growth hormone prevent aging?. New England Journal of Medicine, 348(9), 779-780.
3 Cao, H., Wang, G., Meng, L., Shen, H., Feng, Z., Liu, Q., & Du, J. (2012). Association between circulating levels of IGF-1 and IGFBP-3 and lung cancer risk: a meta-analysis. PloS one, 7(11), e49884.
4 Bartke, A., Brown-Borg, H. M., Bode, A. M., Carlson, J., Hunter, W. S., & Bronson, R. T. (1998). Does growth hormone prevent or accelerate aging?. Experimental gerontology, 33(7), 675-687.
5 Bartke, A. (2005). Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology, 146(9), 3718-3723.
6 Flurkey, K., Papaconstantinou, J., Miller, R. A., & Harrison, D. E. (2001). Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proceedings of the National Academy of Sciences, 98(12), 6736-6741.
7 Flurkey, K., Papaconstantinou, J., Miller, R. A., & Harrison, D. E. (2001). Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proceedings of the National Academy of Sciences, 98(12), 6736-6741.
8 Guevara-Aguirre, J., Balasubramanian, P., Guevara-Aguirre, M., Wei, M., Madia, F., Cheng, C. W., ... & de Cabo, R. (2011). Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Science translational medicine, 3(70), 70ra13-70ra13.
9 Rizza, R. A., Mandarino, L. J., & Gerich, J. E. (1982). Effects of growth hormone on insulin action in man: mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes, 31(8), 663-669.
10 Carroll, P. V., Christ the members of Growth Hormone Research Society Scientific Committee, E. R., Bengtsson, B. A., Carlsson, L., Christiansen, J. S., Clemmons, D., ... & Sonksen, P. H. (1998). Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. The Journal of Clinical Endocrinology & Metabolism, 83(2), 382-395.
11 Marchesini, G., Brizi, M., Morselli-Labate, A. M., Bianchi, G., Bugianesi, E., McCullough, A. J., ... & Melchionda, N. (1999). Association of nonalcoholic fatty liver disease with insulin resistance. The American journal of medicine, 107(5), 450-455.
12 Reaven, G. M. (1988). Role of insulin resistance in human disease. Diabetes, 37(12), 1595-1607.
13 Ginsberg, H. N. (2000). Insulin resistance and cardiovascular disease. The Journal of clinical investigation, 106(4), 453-458.
14 Bansal, T. C., Guay, A. T., Jacobson, J., Woods, B. O., & Nesto, R. W. (2005). ORIGINAL RESEARCH—ENDOCRINOLOGY: Incidence of Metabolic Syndrome and Insulin Resistance in a Population with Organic Erectile Dysfunction. The journal of sexual medicine, 2(1), 96-103.
15 Colao, A., Marzullo, P., Di Somma, C., & Lombardi, G. (2001). Growth hormone and the heart. Clinical endocrinology, 54(2), 137-154.
16 Isaksson, O. G. P., Eden, S., & Jansson, J. (1985). Mode of action of pituitary growth hormone on target cells. Annual review of physiology, 47(1), 483-499.
17 Chang, P. J., Nino-Murcia, M., & Kosek, J. (1990). Polypoid Menetrier's disease associated with acromegaly. Gastrointestinal radiology, 15(1), 61-63.
18 Ehrnborg, C., Bengtsson, B. Å., & Rosén, T. (2000). Growth hormone abuse. Best Practice & Research Clinical Endocrinology & Metabolism, 14(1), 71-77.
19 Collinge, J., Palmer, M. S., & Dryden, A. J. (1991). Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. The Lancet, 337(8755), 1441-1442.
20 Goodbrand, I. A., Ironside, J. W., Nicolson, D., & Bell, J. E. (1995). Prion protein accumulation in the spinal cords of patients with sporadic and growth hormone associated Creutzfeldt-Jakob disease. Neuroscience letters, 183(1), 127-130.
21 Brandel, J. P., Preece, M., Brown, P., Croes, E., Laplanche, J. L., Agid, Y., ... & Alpérovitch, A. (2003). Distribution of codon 129 genotype in human growth hormone-treated CJD patients in France and the UK. The Lancet, 362(9378), 128-130.
22 Yarasheski KE, Campbell JA, Smith K et al. (1992) Effect of growth hormone and resistance exercise on muscle growth in young men. American Journal of Physiology 1992; 262: E261±E267.
23 Yarasheski KE, Zachweija JJ, Angelopoulos TJ et al. (1993) Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. Journal of Applied Physiology 1993; 74: 3073±3076.
24 Deyssig R, Frisch H, Blum WF et al. (1993) Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinologica (Copenhagen) 1993; 128: 313±318.
25 Taaffe DR, Jin IH, Vu TH et al. (1996) Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. Journal of Clinical Endocrinology and Metabolism 1996; 81: 421±425.
26 Meinhardt, U., Nelson, A. E., Hansen, J. L., Birzniece, V., Clifford, D., Leung, K. C., ... & Ho, K. K. (2010). The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational AthletesA Randomized Trial. Annals of internal medicine, 152(9), 568-577.
27 Berggren, A., Ehrnborg, C., Rosén, T., Ellegård, L., Bengtsson, B. A., & Caidahl, K. (2005). Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. The Journal of Clinical Endocrinology & Metabolism, 90(6), 3268-3273.
28 Hansen, M., Morthorst, R., Larsson, B., Dall, R., Flyvbjerg, A., Rasmussen, M. H., ... & Lange, K. H. W. (2005). No effect of growth hormone administration on substrate oxidation during exercise in young, lean men. The Journal of physiology, 567(3), 1035-1045.
29 Lange, K. H. W., Andersen, J. L., Beyer, N., Isaksson, F., Larsson, B., Rasmussen, M. H., ... & Kjær, M. (2002). GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. The Journal of Clinical Endocrinology & Metabolism, 87(2), 513-523.
30 West, D. W., Burd, N. A., Tang, J. E., Moore, D. R., Staples, A. W., Holwerda, A. M., ... & Phillips, S. M. (2010). Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. Journal of Applied Physiology, 108(1), 60-67.
31 Daly, R. M., O'Connell, S. L., Mundell, N. L., Grimes, C. A., Dunstan, D. W., & Nowson, C. A. (2014). protein-enriched diet, with the use of lean red meat, combined with progressive resistance training enhances lean tissue mass and muscle strength and reduces circulating IL-6 concentrations in elderly women: a cluster randomized controlled trial. The American journal of clinical nutrition, 99(4), 899-910.
32 Waters, D. L., Baumgartner, R. N., Garry, P. J., & Vellas, B. (2010). Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update. Clin Interv Aging, 5, 259-270.
33 McNeill, S. H. (2014). Inclusion of red meat in healthful dietary patterns. Meat science, 98(3), 452-460.
34 Sobal, J. (2005). Men, meat, and marriage: Models of masculinity. Food and Foodways, 13(1-2), 135-158.

 

[wsw16]

Furions Qualifications
MPharm MPS ND BScHlthSci (Comp Med & Nutr)

Furions Summary from James Dries

HGH is a peptide hormone produced and secreted in the brain and is expressed in 4 similar forms, acting on all tissues in the body to promote tissue repair. In response to exercise, one particular type is primarily attributed to enhancing muscle growth (it is this specific type that synthetic forms attempt to replicate). HGH produced in the brain stimulates the release of IGF-1 from the liver, which plays a significant role in signalling muscle growth. When produced naturally, both hormones may work by themselves, or together, amplifying the effects of each other. For this reason, people mistakenly believe that administering synthetic versions of HGH and IGF-1 will promote muscle growth.

The way in which HGH is produced in laboratories leads to a slightly different shape and stability of the synthetic HGH molecule. Therefore, its ability to communicate with muscle cells and signal muscle growth is altered (remember the lock and key analogy). Even if measures are taken to make the purest form of HGH, not all of the product will be effective in its intended role due to manufacturing constraints.
In relation to Brads post, this would make sense as synthetic HGH may be very effective at signalling heart and gut growth, but much less effective in enhancing muscle growth due to its reduced ability to signal IGF-1 release within muscles (less compatible). A lesser quality synthetic HGH will most likely compound this problem. As Brad also mentioned, high circulating levels of IGF-1 are not desirable and may have detrimental effects on brain and lung tissue. Therefore, it appears that the optimal levels of HGH and IGF-1 in relation to building muscle, occurs naturally and is optimally stimulated by resistance training (and diet).

Furions Report
I will follow on from Brads article- through a neutral perspective to dissect this contentious and quantitatively negative finding of myogenic/hypertrophic activity as it pertains to applicable pharmacological qualitative analyses.
I will preface this by indicating that it the information presented here is in fact casted through substantiated hypothetical molecular targeting and effector downstream cascades. It is thus collectively theorized- however does indeed form congruence with the comprehensive quantitative results Brad has described.

As a sort of add-on bonus to the topic- I will describe a potential reason for the widely noted (and consequently accepted) discrepancies of approved GH as somatotropin pharmaceuticals vs. unapproved generically labelled GH- as it pertains to the manufacturing processes.
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To examine the pharmacological activity of supraphysiological growth hormone administration for the physique athlete- it would seem most suitable to establish the endogenous fluxes and bioactivity during resistance exercise and then model these against the (then deduced) molecular targets and downstream effectors that may be conducive to myogenesis when using a pharmaceutical.
In doing this, it is pertinent to stipulate that GH, as a pituitary hormone, occurs as a “superfamily” of (now currently identified) 4 different molecular isoforms, these categorized by the weight (20 kDa, non-22 kDa, 44 kDa, and 66 kDa (1). Each isoform appears to bear role in mediating physiological activity during recovery in response to exercise stress (1-4). The pharmaceutical preparations of GH (as somatotropin) occur as only the monomeric 22kDa peptide, hence it is important to make this distinction when scrutinizing the endogenous patterns against exogenous administrations in exercise models and to consider that the complexity is such that no finites or absolutes can yet be made as to the complete pharmacological myogenic activity.

In saying this, associated evidence does suggest that in non-aged, non-obese subjects the more rapid-response patterns and greatest fluxes of endogenous GH associated with anaerobic resistance exercise are actually related to this 22-kDa (immunoreactive GH) isoform (5-8) see figure 1. It is also worth noting that there does appear to be aged and body compositional implications to the magnitude of the responses (7,8).

It is now understood that the growth hormone receptor (GHR) is ubiquitious and through signal transduction can have effect on all tissues (9,10). From a broad analytical examinations, any likely anabolic activity associated with exogenous GH will be confounded by anabolic activity of GH stimulated, hepatic secreted systemically circulating IGF-1. It has been recently identified that the anabolic activities between these two hormones may be in fact independent of each other, potentially additive and in respect to the endogenous patterns; synergistic as it pertains to myogenesis and tissue repair (11). Henceforth for the purposes of distinguishing these two hormones as exogenous preparations, this report will focus on that unique to GH alone.

Cumulative data suggests that the molecular patterns specific with growth hormone administration (or secretion) in combination with resistant exercise are hallmarked by an up regulation of a tissue specific mechanosensitive isoforms of IGF-1 (12,13). These are IGF-1 isoforms literally produced by skeletal muscle, to act locally within the skeletal muscle; a paracrine response (13,14). Skeletal muscle induced IGF undergoes alternative splicing and generates 3 isoforms; IGF1Ea, IGF1Eb and IGF1Ec (15,16). The IGF1Ec isoform, colloquially known as mechano growth factor (MGF) appears the most active and also has recently been implicated as the likely main driver behind the paracrine activity that may have the terminal responsibility for the downstream myogenesis associated with resistance training and subjectively augmented by growth hormone (17,18).
MGF (as IGF-1Ec) has been shown to activate muscle satellite cells, promote myonuclei accumulation and expand myofiber diameter (17,19) whilst growth hormone has independently been shown to rapidly induce expression of MGF in muscle satellite cells in varying models, and may in fact do so in an additive manner with MGF when combined with resistance training (12,13,20).

So to apply this as a theoretical basis, it may be postulated that the MGF response, as induced by the combination of mechanical loading and exogenous GH administration, may activate muscle satellite cells and accrue extra myonuclei as a repair response in greater amplitude than what can occur in normal physiological conditions. This induced state may therefore somewhat override the negative regulators of satellite cells maturation, such as myostatin, that normally halt and shift the satellite cell activation back into the quiescient state and potentially remove a limitation to the mitotic and subsequent myogenesis (21-23).

**Working off this premise- there may be further pharmaceutical methods to exploit this mode of action when considering the systemic IGF-1 implications. This would include the use of insulin and other anabolic compounds- however may need a separate article in itself**
Although it may seem as though this could explain the anecdotally claimed skeletal muscle hypertrophic capacity of growth hormone, these actions alone may not account for any measurable degree of muscle strength increase or performance enhancement- hence may provide some degree of rationale for the consistently negative results observed in the quantitative analyses Brad has cited. This has certainly been comprehensively concluded in related qualitative research (24-26). Additionally as this molecular pathway has not been comprehensively researched so I am really at a stretch here to conclusively say that this is the unique pharmacological property of growth hormone that distinguishes it from all performance and image enhancing drugs.
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Peptide syntheses can be performed via two main methods. The distinction between the methods may account for the discrepancies of subjective quality of approved GH preparation against those unapproved generically labelled.
Peptide synthesis can be performed via amino acid binding- known simply as chemical synthesis. This is generally the cheapest and simplest method for peptide syntheses. It is usually performed with apparatus that literally link the individual amino acid together in a linear manner using catalytic enzymes and chemicals. This permits manufacture of perfectly functional short chain peptides (such as melanotan, GHRPs, ect). For synthesizing long chain peptides with 3 dimensional complex binding this method is limited in creating the tertiary and quaternary conformation patterns often associated with these.

So although the peptide sequence may be correct, it is likely that the shape formed by the extra-sequence binding might not be consistently present, if at all.
Recombinant peptide synthesis differs completely. This involves a live in-cell model usually using strains of bacterial or fungi, whereby the DNA and ribosomal transcriptional activity is stimulated so as to produce and then harvest the desired peptide. The peptide will therefore contain the bioidentical, 3 dimensional structure owing to the presence of the tertiary and quaternary peptide bonding. This is often necessary to the exploit the complete activity of the hormone and given research has not completely elucidated the binding properties of the GH receptor at the skeletal muscle, we must assume that the structural homogeneity is necessary for this binding. This therefore may serve as plausible explanation for the biological activity discrepancies between GH preparations.

As completed synthetic preparations, the stability of each peptide between these manufacturing procedures can also give reason as to the variance in the bioactivity. A peptide synthesized by chemical means tends to be more flexible and therefore more stable in shorter chains (i.e less than 100 residues). This decreases linearly in concert with the increasing number of residues. The reciprocal applies for recombinantly synthesized peptides. As the growth hormone isomer consists of 191 residues- it could be inferred that subsequent manufacturing procedures, including the lyophilisation (freeze drying), could pose detriment to the integrity of the peptide. A lyoprotectant should be used in GH manufacturing to maintain the structural integrity during this process. As result of the presence of tertiary and quaternary bonds, the recombinantly synthesized peptide is much more stable in the presence of a lyoprotectant. The same can be guaranteed for a chemically synthesized peptide, thus it could be well-assumed a percentage may become damaged as result this process.
Hence it may also seem plausible that a greater percentage of the peptide would be damaged using a chemical synthesis process.


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(17) Dai, Z., Wu, F., Yeung, E. W., & Li, Y. (2010). IGF-IEc expression, regulation and biological function in different tissues. Growth Hormone & IGF Research, 20(4), 275-281.
(18) Yi, Q., Feng, J., He, L., Wan, R., Zeng, H., Yang, L., ... & Tang, L. (2017). The structure-function relationships of insulin-like growth factor 1 Ec in C2C12 cells. Cell Adhesion & Migration, (just-accepted), 00-00.
(19) Mavalli, M. D., DiGirolamo, D. J., Fan, Y., Riddle, R. C., Campbell, K. S., van Groen, T., ... & Clemens, T. L. (2010). Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice. The Journal of clinical investigation, 120(11), 4007-4020.
(20) Imanaka, M., Iida, K., Murawaki, A., Nishizawa, H., Fukuoka, H., Takeno, R., ... & Chihara, K. (2008). Growth hormone stimulates mechano growth factor expression and activates myoblast transformation in C2C12 cells. Kobe J Med Sci, 54(1), E46-54.
(21) Goldspink, G. (2012). Age-related loss of muscle mass and strength. Journal of aging research, 2012.
(22) Hill, M., & Goldspink, G. (2003). Expression and splicing of the insulin‐like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. The Journal of Physiology, 549(2), 409-418.
(23) Nederveen, J. P., Joanisse, S., Snijders, T., Ivankovic, V., Baker, S. K., Phillips, S. M., & Parise, G. (2016). Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men. Journal of cachexia, sarcopenia and muscle, 7(5), 547-554.
(24) Snijders, T., Smeets, J. S. J., Kranenburg, J., Kies, A. K., Loon, L. J. C., & Verdijk, L. B. (2016). Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance‐type exercise training. Acta Physiologica, 216(2), 231-239.
(25) Roth, S. M., Martel, G. F., Ivey, F. M., Lemmer, J. T., Tracy, B. L., Metter, E. J., ... & Rogers, M. A. (2001). Skeletal muscle satellite cell characteristics in young and older men and women after heavy resistance strength training. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(6), B240-B247.
(26) Kadi, F., Schjerling, P., Andersen, L. L., Charifi, N., Madsen, J. L., Christensen, L. R., & Andersen, J. L. (2004). The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. The Journal of physiology, 558(3), 1005-1012.

 

[Mr.B66]

Well this isnt what i was expecting. Kinda confused rt now as most of this info is in contrast to what i thought about GH.

 

[colossus25]

Well this isnt what i was expecting. Kinda confused rt now as most of this info is in contrast to what i thought about GH.

Im not contesting what the articles are stating as they both provided references which i didn't really go through to be honest, i just read them at face value. That being said there is a problem with both articles and that is they seem to not be counting in variables like hgh combined with AAS and insulin, they are only talking about hgh on its own. So when he stated in the first article that very little to no muscle mass was built on a 12 week cycle, i was like no shit. Hgh by its self doesn't build very much muscle its when its stacked with other compounds that it makes all the difference in the world. Also another variable to consider is the amount of time they ran hgh in the studies they both referenced. 12 weeks is about when hgh actually starts to put in work IME. These studies should be run for 24 weeks as opposed to such a short period of time.

From personal experience i can tell you GH makes a hell of a big difference when ran along side a cycle. What these articles are talking about is risk vs reward, which is basically all PEDs really. If we sit here and talk about all the known side effects of every PED out there you would probably never pick up a syringe again lol.

 

[wsw16]

Im not contesting what the articles are stating as they both provided references which i didn't really go through to be honest, i just read them at face value. That being said there is a problem with both articles and that is they seem to not be counting in variables like hgh combined with AAS and insulin, they are only talking about hgh on its own. So when he stated in the first article that very little to no muscle mass was built on a 12 week cycle, i was like no shit. Hgh by its self doesn't build very much muscle its when its stacked with other compounds that it makes all the difference in the world. Also another variable to consider is the amount of time they ran hgh in the studies they both referenced. 12 weeks is about when hgh actually starts to put in work IME. These studies should be run for 24 weeks as opposed to such a short period of time.

From personal experience i can tell you GH makes a hell of a big difference when ran along side a cycle. What these articles are talking about is risk vs reward, which is basically all PEDs really. If we sit here and talk about all the known side effects of every PED out there you would probably never pick up a syringe again lol.

But what is the evidence that when stacked with other things it works? if it doesn't provide much skeletal muscle growth by itself why would it all of a sudden do it when when stacked with other things? they can't talk about those variables because there is no evidence of it. If they started talking about anecdotal experiences than it would discredit their whole article so they can't really mention those things without facts. Unfortunately those studies don't exist and probably never will. Though the closest you can get is that WADA study referenced with sprinters using 250 mg of exogenous test alongside the hgh. A few studies were ran for longer than 12 weeks. But regardless of time it shouldn't take hgh 12 weeks for it to show signs of working, evidence of it working should be present by then and afterwards estimations can be done by those conducting the studies.

They're not only talking about risk vs reward, Brad goes onto quite a bit of depth covering it's effects (or lack there of in his opinion) on skeletal muscle growth.

I disagree with the articles when they mention it doesn't work (particularly Brad) but I don't disagree that it is overrated in terms of a PED. I've used it extensively including cycles of 6 months or more on 10 iu ed of legitimate pharma alongside anabolics and insulin. Did I get results yeah sure. But it hardly made a "world of difference". Insulin made the biggest difference and I'd argue that is a lot more effective for hypertrophy. Hgh in my opinion is not the holy grail it's made out to be but it is useful though I do think too many people confuse it's effects on water retention as muscle gain. I don't think I'll ever run another cycle higher than 5-6iu it is simply not needed and I have to disagree with people who push much higher dosages.

 

[colossus25]

But what is the evidence that when stacked with other things it works? if it doesn't provide much skeletal muscle growth by itself why would it all of a sudden do it when when stacked with other things? they can't talk about those variables because there is no evidence of it. If they started talking about anecdotal experiences than it would discredit their whole article so they can't really mention those things without facts. Unfortunately those studies don't exist and probably never will. Though the closest you can get is that WADA study referenced with sprinters using 250 mg of exogenous test alongside the hgh. A few studies were ran for longer than 12 weeks. But regardless of time it shouldn't take hgh 12 weeks for it to show signs of working, evidence of it working should be present by then and afterwards estimations can be done by those conducting the studies.

They're not only talking about risk vs reward, Brad goes onto quite a bit of depth covering it's effects (or lack there of in his opinion) on skeletal muscle growth.

I disagree with the articles when they mention it doesn't work (particularly Brad) but I don't disagree that it is overrated in terms of a PED. I've used it extensively including cycles of 6 months or more on 10 iu ed of legitimate pharma alongside anabolics and insulin. Did I get results yeah sure. But it hardly made a "world of difference". Insulin made the biggest difference and I'd argue that is a lot more effective for hypertrophy. Hgh in my opinion is not the holy grail it's made out to be but it is useful though I do think too many people confuse it's effects on water retention as muscle gain. I don't think I'll ever run another cycle higher than 5-6iu it is simply not needed and I have to disagree with people who push much higher dosages.

Lack of evidence doesn't mean that it isn't true. I do believe there is a synergistic effect between hgh and anabolic steroids, even more so with insulin (admittedly this is conjecture). I understand why they left it out of the article as a whole but they should have stated that there are variables unaccounted for with no evidence to prove or disprove them. I do agree with you about the higher doses we see a lot of idiots taking. I don't run more than 6ius and don't plan too anytime soon unless i increase that drastically in body weight and musculature that it demands it.

 

[wsw16]

Lack of evidence doesn't mean that it isn't true. I do believe there is a synergistic effect between hgh and anabolic steroids, even more so with insulin (admittedly this is conjecture). I understand why they left it out of the article as a whole but they should have stated that there are variables unaccounted for with no evidence to prove or disprove them. I do agree with you about the higher doses we see a lot of idiots taking. I don't run more than 6ius and don't plan too anytime soon unless i increase that drastically in body weight and musculature that it demands it.

Furion touched on it a little bit here:

So to apply this as a theoretical basis, it may be postulated that the MGF response, as induced by the combination of mechanical loading and exogenous GH administration, may activate muscle satellite cells and accrue extra myonuclei as a repair response in greater amplitude than what can occur in normal physiological conditions. This induced state may therefore somewhat override the negative regulators of satellite cells maturation, such as myostatin, that normally halt and shift the satellite cell activation back into the quiescient state and potentially remove a limitation to the mitotic and subsequent myogenesis (21-23).

**Working off this premise- there may be further pharmaceutical methods to exploit this mode of action when considering the systemic IGF-1 implications. This would include the use of insulin and other anabolic compounds- however may need a separate article in itself**
Although it may seem as though this could explain the anecdotally claimed skeletal muscle hypertrophic capacity of growth hormone, these actions alone may not account for any measurable degree of muscle strength increase or performance enhancement- hence may provide some degree of rationale for the consistently negative results observed in the quantitative analyses Brad has cited. This has certainly been comprehensively concluded in related qualitative research (24-26). Additionally as this molecular pathway has not been comprehensively researched so I am really at a stretch here to conclusively say that this is the unique pharmacological property of growth hormone that distinguishes it from all performance and image enhancing drugs.

I tend agree more on his side of it as he seems to be more pro hgh than Brad and almost admits there could be those benefits on skeletal muscle with those variables you mentioned.

 

[colossus25]

So to apply this as a theoretical basis, it may be postulated that the MGF response, as induced by the combination of mechanical loading and exogenous GH administration, may activate muscle satellite cells and accrue extra myonuclei as a repair response in greater amplitude than what can occur in normal physiological conditions. This induced state may therefore somewhat override the negative regulators of satellite cells maturation, such as myostatin, that normally halt and shift the satellite cell activation back into the quiescient state and potentially remove a limitation to the mitotic and subsequent myogenesis (21-23).

**Working off this premise- there may be further pharmaceutical methods to exploit this mode of action when considering the systemic IGF-1 implications. This would include the use of insulin and other anabolic compounds- however may need a separate article in itself**

A separate article based on theory indeed.

I found that first bit particularly interesting because i read an article not too long ago about the possible myostatin blocking benefits of HGH.

 

[colossus25]

@wsw16

Myostatin is a skeletal muscle target of growth hormone anabolic action. - PubMed - NCBI

 

[Mr.B66]

The part that was a bit of a surprise to me was when it was stated that GH isnt anti aging, in fact it has the opposite affect. Ive seen many people state that they felt their skin looked better ect.... Also it was stated that no one in the gh group lost body fat. Now this is where i have a disagreement. I know through personal experience that gh works great at dropping BF. even if you dont have the cleanest diet.

 

[colossus25]

The part that was a bit of a surprise to me was when it was stated that GH isnt anti aging, in fact it has the opposite affect. Ive seen many people state that they felt their skin looked better ect.... Also it was stated that no one in the gh group lost body fat. Now this is where i have a disagreement. I know through personal experience that gh works great at dropping BF. even if you dont have the cleanest diet.

I agree with that part actually. What categorizes something as anti-aging? Hgh can improve skin health and has a tightening effect, maybe thats what people consider anti-aging.

Now dropping bodyfat on gh is a different story. IME gh is great for nutrition partitioning and does have a synergistic effect especially when ran with tren that really makes leaning out a walk in the park. Couple that with its skin health and tightening benefits and its a win win. Again this is where running it for 6 months as opposed to shorter periods also makes a difference i found.

 

[Jeffg353]

I don't think this article was mentioned (i apologize if it was but it's late and a lot to read) but it does seem to back up their claims.

Regulation of muscle mass by growth hormone and IGF-I

 

[colossus25]

@mands this is a good thread for you to hop in and drop some knowledge bombs lol

 

[Mr.B66]

I agree with that part actually. What categorizes something as anti-aging? Hgh can improve skin health and has a tightening effect, maybe thats what people consider anti-aging.

Now dropping bodyfat on gh is a different story. IME gh is great for nutrition partitioning and does have a synergistic effect especially when ran with tren that really makes leaning out a walk in the park. Couple that with its skin health and tightening benefits and its a win win. Again this is where running it for 6 months as opposed to shorter periods also makes a difference i found.

I think most would consider healthier tighter skin " anti aging" but of course nothing can turn back the clock, if your 50, your 50.
But the fat dropping is deff real. I have run many cut cycles over the years, none was as easy or more muscle sparing as when i ran gh during the cut. As you say, it was" a walk n the park" compared to without it.

 

[Mr.B66]

I agree with that part actually. What categorizes something as anti-aging? Hgh can improve skin health and has a tightening effect, maybe thats what people consider anti-aging.

Now dropping bodyfat on gh is a different story. IME gh is great for nutrition partitioning and does have a synergistic effect especially when ran with tren that really makes leaning out a walk in the park. Couple that with its skin health and tightening benefits and its a win win. Again this is where running it for 6 months as opposed to shorter periods also makes a difference i found.

And i wasnt saying i was surprised that it was stated that it wasnt
" anti aging", i was surprised when it stated that it had the
" opposite " affect. With that im assuming they mean it speeds the aging process up.

 

[colossus25]

I think most would consider healthier tighter skin " anti aging" but of course nothing can turn back the clock, if your 50, your 50.
But the fat dropping is deff real. I have run many cut cycles over the years, none was as easy or more muscle sparing as when i ran gh during the cut. As you say, it was" a walk n the park" compared to without it.

Thats what i guess people would consider anti-aging. Its more of a sales pitch by hormone replacement clinics IMO.

And yes thats always been my experience with running gh on a caloric deficit. Also vice-versa when bulking, i find i put on more muscle mass when i bulked on gh.

And i wasnt saying i was surprised that it was stated that it wasnt
" anti aging", i was surprised when it stated that it had the
" opposite " affect. With that im assuming they mean it speeds the aging process up.

Physiologically i can see why they say gh has the opposite effect but i feel that is also very vaguely stated.

 

[wsw16]

The part that was a bit of a surprise to me was when it was stated that GH isnt anti aging, in fact it has the opposite affect. Ive seen many people state that they felt their skin looked better ect.... Also it was stated that no one in the gh group lost body fat. Now this is where i have a disagreement. I know through personal experience that gh works great at dropping BF. even if you dont have the cleanest diet.

The pro aging effects of hgh according to the article by Brad are more pronounced on organ tissue as according to him that's where raised systemic igf levels can pronounce most of it's negative effects. People may refer to hgh giving them clearer skin etc but if you look closely at those who use hgh for extensive periods you'll notice they start to develop thicker/denser skin particularly in facial areas which is not good at all.

Hgh is great at mobilising fat, however it's not great at burning fat to put it simply as it's not a thermogenic so it's effects on oxidising fat aren't that good. It does make dropping body fat easier though under the correct circumstances/conditions. That's why it can be so effective with things like tren, dnp, clen and other substances that raise your metabolic rate. Or of course with increased cardio/exercise, that's why you hear people saying it's very effective taken pre fasted cardio as it will release extra fatty acids to be burned off.

@wsw16

Myostatin is a skeletal muscle target of growth hormone anabolic action. - PubMed - NCBI

Great study thanks for posting, interesting read

 

[colossus25]

I don't think this article was mentioned (i apologize if it was but it's late and a lot to read) but it does seem to back up their claims.

Regulation of muscle mass by growth hormone and IGF-I

Very good article. Admittedly i jumped around a bit and skipped over some of the stuff that was discussed in the others.

"The mechanisms that lead to muscle adaptation to overload are not completely understood. Neither are those that regulate muscle mass development and maintenance. GH and IGF-I clearly play a role in muscle development pre- and postnatally. In GHD adults, there is evidence that serum GH affects muscle mass maintenance, but in healthy adults neither GH nor IGF-I has or enhances the hypertrophic effects of exercise. In contrast, much evidence supports the hypertrophic effect of autocrine/paracrine IGF-I in animals and suggests that it may play a role in adaptation to overload in both animals and humans. Increased muscle expression of IGF-I also enhances the effects of training in animals. Local injection of GH or IGF-I protein or plasmids is effective in animal models and may eventually be used with therapeutic ends. There is evidence for an effect of GH on other performance parameters that is related to increased lean body mass as opposed to increased skeletal muscle mass."

The most important thing to note here in the conclusion is the first couple of sentences. Which we have been discussing. GH on its own is not a great mass builder but as mentioned before when stacked with other compounds it does seem to really promote better muscle growth. What we have been discussing is the variables and anecdotal evidence of why that is. I posted a study which seems to show GH may have myostatin inhibiting qualities which obviously would be HUGE in promoting further muscle growth.

 

[wsw16]

And i wasnt saying i was surprised that it was stated that it wasnt
" anti aging", i was surprised when it stated that it had the
" opposite " affect. With that im assuming they mean it speeds the aging process up.

That's essentially what he means

"Growth hormone promotes proliferation and mitosis of various tissues including cancer lines. It upregulates cell turnover which in effect is like photocopying copies of photocopies. Rather than cells spending more time in rest and repair phase of the cell cycle, they are quickly pushed through the cycle proliferating errors."

 

[colossus25]

The pro aging effects of hgh according to the article by Brad are more pronounced on organ tissue as according to him that's where raised systemic igf levels can pronounce most of it's negative effects. People may refer to hgh giving them clearer skin etc but if you look closely at those who use hgh for extensive periods you'll notice they start to develop thicker/denser skin particularly in facial areas which is not good at all.

Hgh is great at mobilising fat, however it's not great at burning fat to put it simply as it's not a thermogenic so it's effects on oxidising fat aren't that good. It does make dropping body fat easier though under the correct circumstances/conditions. That's why it can be so effective with things like tren, dnp, clen and other substances that raise your metabolic rate. Or of course with increased cardio/exercise, that's why you hear people saying it's very effective taken pre fasted cardio as it will release extra fatty acids to be burned off.



Great study thanks for posting, interesting read

Yes thats what i was referring to when i made the statement about physiological changes. I don't see how that is necessarily the opposite effect of anti-aging but most definitely a negative one.

And yes again, hgh on its own is not great at any particular one thing but when ran with other compounds it is pretty awesome if i do say so myself.