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Body composition response to exogenous GH in highly conditioned adults

Body composition response to exogenous GH in highly conditioned adults

STUDY, demonstrating positive body composition changes in highly trained athletes w/ 2g/kg per day protein intake & 8iu of GH 3x per week (EOD), w/ no other compounds.

NOTE: Protropin 1mg = 3iu or 1iu = 333mcg
EOD dose (3x per week) in the following study: 2.67mg or 8iu
Weekly total dose = 8mg or 24iu

Summary results:
FFW = fat free Weight
FW = fat Weight

The weight results are in Kilograms not pounds.

Body composition response to exogenous GH during training in highly conditioned adults, D. M. Crist, J Appl Physiol 65: 579-584, 1988


The effects of biosynthetic methionyl-human growth hormone (met-hGH) on body composition and endogenous secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I) were studied in eight well-trained exercising adults between 22 and 33 yr of age for 6 weeks.

Dosing & Administration of HGH:

The met-hGH (experimental) treatment consisted of 8.0 mg (2 U/mg) per week of methGH (Protropin; Genentech, San Francisco, CA), which was divided into three doses (2.67 mg/dose) and delivered on alternate days (3 days/wk) in 0.5 ml of bacteriostatic diluent. Because of differences in the body weights of the subjects, the relative dose range varied between 0.03 and 0.05 mg/kg per injection. Injections were given between 0800 and 1500, and their delivery was rotated among four to six sites throughout the study period. Treatments were administered on a double-blind basis with neither the experimental subject nor the person administering the injections knowing which treatment was being delivered. The total weekly dose of met-hGH used in this study (8.0 mg) was considered supraphysiological, since the spontaneous release of human GH during a 24-h period is purportedly -0.68 mg (4.8 mg/wk) in men and 0.79 mg (5.5 mg/wk) in women (30), similar to amounts reported by others (6).


In the present study, we found that alternate-day treatment with met-hGH altered body composition in highly conditioned, exercising adults by increasing FFW (fat free weight), decreasing %fat, and increasing FFW (fat free weight)/FW (fat weight). These changes were significantly greater than those produced by exercise alone.

Moreover we found that supraphysiological amounts of met-hGH were sufficient to significantly elevate circulating concentrations of IGF-I in all our subjects, confirming that the changes in body composition were indeed due to real alterations produced in vivo by the hormone treatment.

Suppression of endogenous HGH

It has been reported previously that exogenous GH will suppress endogenous release of the hormone (19,23) and that this effect may be mediated in part by elevated levels of IGF-I (23). On a preliminary basis, we found that treatment for 6 wk with supraphysiological doses of met-hGH produced an impaired endogenous GH response to stimulation in some, but not all, of our subjects. This variable response may be related to the amount of hormone used in the study. Although a significant group elevation in IGF-I levels occurred during the met-hGH treatment, this response was still below the upper limit of normal (2.20 U/ml) for the study group. Thus it is plausible that the treatment dose of met-hGH used and the subsequent moderate increase in IGF-I levels led to feedback suppression of endogenous GH release in five of the seven subjects measured for this effect, whereas these physiological events were insufficient to produce this effect in two of the subjects.

Intense exercise increases sensitivity to HGH??

…One possible explanation for the disparity between our findings and those of others (25, 26) is that the stress of long-term, intensive exercise training could induce alterations in vivo, which might potentiate tissue sensitivity to the physiological actions of GH (2). In any case, it is clear from our findings that supraphysiological doses of met-hGH increased circulating concentrations of IGF-I and increased FFW (fat free weight) and decreased FW (fat weight) in highly conditioned, exercising adults.

Soft-tissue Overgrowth?

There are two principal adverse reactions associated with excessive amounts of human GH, carbohydrate intolerance, and soft-tissue overgrowth. In the present study, we measured fasting blood glucose levels periodically throughout each treatment and found no real changes suggestive of a hyperglycemic response to methGH. Because soft-tissue overgrowth is associated with abnormally high levels of IGF-I, the normal responses observed suggest that the chance for soft-tissue overgrowth occurring in our subjects was minimal. However, it is unreasonable to conclude that use of met-hGH is safe as an adjunct to exercise in healthy adults until more subjects are studied over longer periods of time and with more stringent tests for detecting changes in glucose tolerance and soft-tissue overgrowth.

Diet used

To avoid compromising the dietary requirements for optimal tissue anabolism during the met-hGH treatment, our subjects ingested between 2.05 and 2.10 g/kg a day of protein and a minimum number of kilocalories to maintain body weight. The kilocaloric requirement removed the potential bias from a dietary-induced FW loss.

In Conclusion

We conclude that treatment with supraphysiological doses of met-hGH will significantly alter body composition in adults who are highly conditioned from years of exercise training. The magnitude of this effect, however, is dependent in part on the amount of hormone given per body weight of the individual rather than endogenous GH secretory status. Changes in body composition are directly related to met-hGH administration, but the manifestations of treatment may be mediated in part by increased production of IGF-I or other GH-dependent serum anabolic factors. Moreover, supraphysiological treatment with met-hGH in exercising adults may produce impairments in the stimulated release of endogenous GH in some individuals.

The above study is one of those rare studies that is directly applicable to bodybuilding. One to add to your knowledge base.

Things to note:

- GH w/o exogenous anabolics/androgens and w/o insulin increased muscle mass and lowered bodyfat % over 6 weeks.

- The participants were healthy young women & men.

- Participants were highly trained athletes who had no expectation of losing body weight nor gaining bodyweight because these parameters were stable due to their current conditioning.

- The dosing was every other day, only 3x per week.

- The daily dosing was 8iu for a weekly total of 24iu.

- This was sufficient to elevate IGF-1 levels but not to the point where they contributed to soft-tissue growth.

- No soft-tissue growth (such as gut) occurred.

- Protein intake was 2g/kg but diet was maintenance (body recomposition on a maintenance diet).

- IGF-1 was underscored as the primary suppressant of natural GH release and it was at a level where after 6 weeks five of the seven participants had suppressed natural GH release.

- the study’s estimation of what the normal level of GH is in men & women is too high because the study was done in 1988 when assays were not sensitive enough to distinguish between GH ligands, GH-binding protein and GH fragments. (This has no effect on the results …just a note not to rely on their stated estimate in that regard.)

What can you (and I too of course) learn from this, that goes against convention?

“GH is not anabolic w/o insulin” does not mean that you need exogenous insulin.

A sufficient amino acid pool is likely required.

You can both gain muscle & lose fat at a maintenance caloric intake w/ GH & training.

Six weeks is a sufficient amount of time to make positive changes.

You don’t need beaucoup amounts of GH!!!!


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Melanotan Melanotan II


Melanotan (MT) and Melanotan II (MT-II) are both analogs of the alpha-melanocyte stimulating hormone (α-MSH) which is produced within the pituitary gland. Along with other melanocortins, they are responsible for various internal human functions including skin and hair pigmentation, appetite, libido and physical sexual arousal. Whilst these effects have been observed in both sexes, it is worth noting that increases in libido and sexual function are exclusive to MT-II. This article will primarily look at the tanning and pigmentation properties of the hormone, though it would be foolish to ignore the other effects which are discussed further in the Side Effects section.



Background   Melanotan (MT) and Melanotan II (MT-II) are both analogs of the alpha-melanocyte stimulating hormone (α-MSH) which is produced within the pituitary gland. Along with other melanocortins, they are responsible for various internal human functions including skin and hair pigmentation, appetite, libido and physical sexual arousal. Whilst these effects have been observed in both sexes, it is worth noting that increases in libido and sexual function are exclusive to MT-II. This article will primarily look at the tanning and pigmentation properties of the hormone, though it would be foolish to ignore the other effects which are discussed further in the Side Effects section.

Prompted by ultraviolet (UV) exposure, α-MSH release consequently stimulates production of melanin from the melanocytes within the skin. Melanin, as I’m sure you are aware, is a brown pigment and responsible for the tanning of the skin. Simply put, more α-MSH means more melanin, resulting in greater skin pigmentation. Since bodybuilding is such an aesthetic pursuit, and with darker skin that accentuates muscularity, it’s little wonder that these drugs are in such high demand.


Currently, analogs based upon MT and MT-II are undergoing clinical trials, with a view to bringing medicinal products to market. These synthetic variants of α-MSH were developed at the University of Arizona during the 1980s. Australian based Clinuvel Pharmaceuticals Limited have marketing rights to MT (CUV1647), with their primary market being individuals with adverse reaction to UV exposure. This includes those with Polymorphous Light eruption (PLE/PMLE) and Actinic Keratosis (AKs or solar keratosis) where skin is intolerant to UV and characterised by severe sores, lumps, itching or burning sensations, or dry skin lesions/growths. You might think that this peptide would be an ideal treatment for pure albinos. However, these individuals are generally not deficient in α-MSH, but instead are have zero melanocyte receptor binding. Therefore, merely increasing circulatory levels of α-MSH or its analogs is futile. Palatin Technologies Inc. based in the United States, has instead focused on an analog of MT-II. Licensed as Bremelanotide (formerly PT-141), this is aimed squarely at the sexual dysfunction market, more specifically, erectile dysfunction (ED) in men. However, early (phase I & II) clinical trials have also been performed using female subjects with results being described by the company as ‘encouraging’.

Both Melanotan and Melanotan II have been shown in the clinical setting to increase pigmentation without exposure to UV, a feature that is also confirmed anecdotally by users that report tanning in areas of the body that would seldom see the light of day! However, the process of tanning is greatly expedited by UV exposure. It is worth noting that tanning effects may not be uniform throughout the skin. This is in part due to the half life and distribution of the drug itself, but primarily in response to the concentration of melanocytes within certain areas of the skin. Most will notice the greatest tanning effect on the face, arms, abdominal region. Interestingly, the genitals have one of the highest concentrations of melanocytes enabling these particular areas to respond very well to the peptide in conjunction with UV exposure.

As I’m sure you can appreciate, the development of these peptides has not gone unnoticed by the general population and as a result, there has been an explosion of suppliers looking to exploit such demand, with the peptides being formulated and originating largely from China. Although not classed as controlled substances in the UK, they are viewed as medicinal substances by the MHRA (Medicines and Healthcare products Regulatory Agency). While this means that you can legally possess them for personal use, sale or supply is dependant upon whether the product holds a Marketing Authorisation (product licence) valid for the UK. Since I cannot find any evidence of this, nor would I expect to at this juncture of development, suppliers plying their trade within the UK are doing so illegally.   Suggested Cycles/Uses   If you look hard enough out there, you will find some weird and wonderful dosaging schedules whereby the user calculates their daily dosage by multiplying their bodyweight by a cofactor. Perhaps this approach has been adopted since this has been the method employed in the ongoing clinical studies. Typically, this type of formula would suggest a dose of 1mg of MT-II per day for someone weighing in at a mere 110lb (50kg). The cynical among us might be forgiven for thinking that these formulae are constructed by those with a personal interest in the sale of the product as I believe this to be more than necessary to achieve a great result. Indeed, there are many instances whereby users feel they have become too dark. While I have no problem with a bodyweight dosage scale in principle, I can’t help thinking that it’s not only unnecessary (particularly for the mathematically challenged), but also avoids the ability to gradually increase dosages from a relatively low level; something which I would advocate to assess individual tolerance levels to side effects, especially in the case of MT-II.

Clinical trials to determine efficacy of the drugs have typically used dosages up to 0.21mg/kg daily for Melanotan (16mg for a 75kg (165lb) individual), and up to 0.03mg/kg daily for Melanotan II (2.25mg for a 75kg (165lb) individual). More typically however, trials have used the dosages of 0.16mg/kg (12mg) and 0.025mg/kg (1.875mg) respectively. At this level of dosage, one such study involving Melanotan indicated the following incidences of side effects from subjects: • Nausea 85%

• Facial Flushing 75%

• Fatigue 44%

• Vomiting 26%

• Injection site reactions 13%

• Zero incidence of erections

• No change in vital signs or haematological parameters, blood biochemistry (liver and renal function)

As is the case with any drug use, the user is ideally looking to minimise unwanted side effects, whilst still achieving an acceptable outcome. With this in mind, I would suggest that a tapering up of dosages is used in order to assess the individual’s personal tolerance to the side effects.

Both MT and MT II can be used for extended periods, whereby there is an initial daily administration of perhaps 2-3 weeks or until desired level of pigmentation has been achieved, followed by a maintenance phase of two injections per week.

Melanotan:  Start with a dose of 1mg daily for the first two or three days and, if level of side effects permit, look to increase dosage by 0.25mg every day over the next several days until you reach a daily dosage of 2-3mg. This level should be adequate for most users, though some may wish to increase yet further, perhaps as high as 5mg daily in order to achieve a very deep tan. A maintenance phase as described above is then used.

Melanotan II:  Start with a dose of 0.25mg. If side effects (primarily nausea) are not proving troublesome, attempt to increase daily dosage by 0.25mg where possible, until you reach 1-1.5mg daily. Most have found that this level will yield a very pleasing result and I can’t see much point in increasing too much further unless a very deep tan was desired. As with Melanotan, once the desired level of tanning is reached, a maintenance phase is used.

Administration  Both MT and MT II are currently supplied as white lyophilised powder contained in a sealed multi-use vial. The peptide is susceptible to temperature degradation and should be shipped preferably with an ice pack though contrary to popular belief, the rate of degradation is very slow (weeks) in its powder form, so there’s no need to be alarmed if yours wasn’t shipped in this manner or you are unable to collect your package from a depot for a day or two. Once delivered, the powder is best stored in a freezer, or refrigerated if this is not possible.

To prepare for injection, it must be reconstituted with bacteriostatic water. You may use anything between 1ml and 5ml of water for your vial. Dependant upon the amount of water used will determine the concentration of your solution. For example, a 10mg vial of Melanotan II mixed with 1ml of water will provide a solution of 10mg per 1ml (10mg/ml). This means that a 1mg dose will require a shot of 0.1ml. Bearing in mind that the recommended starting dose is 0.25mg, using the example above, the actual volume of the shot would be 0.025ml (¼ of 1 tenth of a ml). This is a very small volume and very difficult to accurately dose even with a 0.5ml insulin syringe. Therefore, at least until your dosages have increased, it is suggested that you use more water for your vial.

An example of a good solution would be to mix 10mg of Melanotan II powder with 4ml of bacteriostatic water. This now provides:

10mg/4ml or 1mg/0.4ml or 0.25mg/0.1ml

0.1ml can be accurately measured using a 0.5ml or 1ml syringe.

Obviously, as your dosages become higher, you may dilute subsequent vials with lower amounts of water to reduce the volume of each shot. I would recommend that when you are using a dosage of 1mg, you reconstitute the vial with 1ml or 2ml of water so that each shot will be 0.1ml or 0.2ml respectively.

If you are using insulin syringes which have short needles, you will need to enter the skin at 90°. to the skin, otherwise you can inject as shown in the illustration above with a 29 or 30 gauge, 0.5″ needle.

I would suggest that you use standard 1ml syringes to which you can interchange needles as required. By doing so, you are able to attach any gauge/length you want to reconstitute and draw the solution (I use a 25guage 1″ needle). Once done, simply attach your suitable needle for the injection. Following the injection, ensure that you pull back the plunger a little to ‘reclaim’ the solution that is contained within the needle itself. The syringe/needle is then placed in the refridgerator for storage until your next injection is due whereby you will attach a brand new injection needle. This process is repeated until you have administered all of the solution in that particular syringe.

Alternatively, you may pre-load insulin syringes and refrigerate until needed. However, because they have non-detachable needles, this can be quite cumbersome as they require loading from the rear.

Instability of the peptide is a much greater issue once reconstituted so you don’t want it sitting in the fridge for months on end. Ideally one 10mg vial of MT-II could be shared by two people (each having their own syringe/needles) so even during the maintenance phase of two injections per week of 1mg each; the longest it will be reconstituted for is 2.5 weeks.   Major Differences

I’m guessing by now the question on most people’s mind would be which of the two is better? The short answer is Melanotan for the obvious reason that it facilitates tanning with limited side effects. It is for this reason that this analogue is being trialled with a view to bringing it to market by Clinuvel. They would be faced with an almost impossible mission had they chosen instead MT-II to develop and place before the regulatory authorities for approval. This is due to the host of extra side effects commonly encountered by users of this analogue, perhaps also coupled with the fact that the side effects that are shared with Melanotan appear more pronounced. However, in terms of monetary cost, and perhaps also a desire to experience and utilise the other side effects, most prospective users will choose Melanotan II.

Melanotan’s peptide structure is very closely matched to that of our endogenously produced alpha-melanocyte stimulating hormone (α-MSH). It is a specific agonist of the melanocortin-1 receptor (MC-1R) which is primarily responsible for skin colour and is found on melanocyte cells.

Melanotan II on the other hand has a much shorter sequence of amino acids and because of this quite pronounced change in length and structure, is an agonist of the range of melanocortin receptors. Perhaps more importantly, binding at receptors other than MC-1R is far greater than that of Melanotan. This ‘shotgun effect’ agonism of the full spectrum of different melanocortin receptors results in some effects that are only witnessed from MT-II. Most notably, increases in sexual arousal are due to MT-II’s activation of MC-3R and MC-4R.

Because the amino acid sequence is much shorter in the case of MT-II, there is therefore a much greater density of peptide chains than is present using MT within a given set weight. Although the receptor binding affinity of MT-II may not be quite as effective, there will be much more peptide chains than for MT on a mg for mg basis so effectively you require much less in terms of milligram weight of Melanotan II to achieve similar results. This accounts for the wide difference in suggested dosages for each peptide and of course, makes MT-II a much cheaper proposition

Effects / Side Effects


Melanotan II

Skin pigmentation

Skin pigmentation



Appetite suppression

Appetite suppression

Flushing (esp. facial)

Flushing (esp. facial)









New mole appearance or darkening

New mole appearance or darkening



White patches

White patches

Increased libido

Physical sexual arousal

Anaphylactic shock?

Of the above listed effects/side effects, it is worth bearing in mind that the prevalence and severity are witnessed to a greater degree from Melanotan II. Indeed, most will find Melanotan very comfortable to use, typically only experiencing minor nausea, appetite suppression and flushing.

Although side effects do become less troublesome with each administration of MT or MT-II, most users will experience at least some of the side effect to varying degrees, most commonly nausea, appetite suppression, facial flushing and dull headaches. These will typically become apparent within a few minutes of administration but can last for many hours. In the case of MT-II, increases in libido are often seen in conjunction with outwardly physical signs of sexual arousal whereby the male user experiences prolonged periods of increased blood flow to the penis. This particular side effect does not diminish in severity over time and instances of occurrence are to be expected throughout the period of MT-II use. As I’m sure you can appreciate, this aspect may prove embarrassing and perhaps quite uncomfortable, so I must stress again the importance of building dosage up gradually to assess personal tolerance and susceptibility.

Some users will notice the new appearance of freckles as these particular areas of skin have increased melanin. The good news is that as the tan is developed, the visual appearance of them will diminish, probably completely. Moles commonly become darker too as these are actually highly concentrated clusters of melanocytes. Both of these occurrences will reverse some time after discontinuation of the peptide and suntanning is ceased.

In addition to freckles and mole changes, there are fairly rare reports of a phenomenon called hyperpigmentation. This is typified by blotches of darkened skin, normally much larger than regular moles. Not all incidences of hyperpigmentation are attributable to increased melanocyte activity even though their appearance may only become apparent during melanocortin receptor agonism by Melanotan I or II. This condition is specifically referred to as diffuse hyperpigmentation, with many possible underlying causes or disorders including Addison’s disease, haemochromatosis, hyperthyroidism and certain medications which may induce phototoxic reactions.

Previously unseen white spots or white patches of skin may also become apparent as the tan deepens. Again, this is not thought to occur as a direct result of using Melanotan, rather it merely uncovers the underlying condition. There are a range of actual causes. White spots (typically 2-5mm in size) may be the result of Idiopathic guttate hypomelanosis where there are reductions in the number of melanocytes and melanin in those particular areas. Larger white areas of skin may be due to Tinea versicolor which is a fungal infection caused by the yeast Malassezia furfur which is found on the skin and is not normally troublesome. Treatment would normally include an oral or topical anti-fungal though it may take many weeks for the skin tone to become consistent with surrounding areas.

It has been suggested that due to the greater difference of MT-II to our own α-MSH, there is a greater chance of the body to view the peptide as a ‘foreign body’ and produce an allergic response. This could potentially trigger anaphylaxis, a potentially life threatening situation whereby large amounts of histamine are produced by the body which can lead to a host of effects including severe bronchoconstriction and rapid drops in blood pressure.

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