What is growth hormone?

Synthetic Growth Hormone is an artificially created hormone "identical" to the major naturally produced (endogenous) isoform. It is often referred to by its molecular mass which is 22kDa (kilodaltons) and is made up of a sequence of 191 amino acids (primary structure) with a very specific folding pattern that comprise a three-dimensional structure (tertiary structure). This tertiary structure is subject to potential shape change through a process known as thermal denaturation. While many labs are capable of generating growth hormone (GH) with the proper primary structure not all will be capable of creating a tertiary structure identical to the major naturally occurring growth hormone. The tertiary structure can determine the strength with which the growth hormone molecule binds to a receptor which will in turn affect the "strength" of the intracellular signaling which mediates the events leading to protein transcription, metabolism, IGF-1 creation, etc. It is this inconsistency that accounts in part for the differences in effectiveness of various non-pharmaceutically produced synthetic growth hormone.

Naturally produced Growth Hormone is produced in the anterior pituitary and to a far lesser extent in peripheral tissue. It is made up of a blend of isoforms the majority of which is the 22kDa (191 amino acid) variety with which most are familiar. In addition an isoform that is missing the 15 amino acids that interact with the prolactin receptor is also produced. This form is known as 20kDa and although it binds differently to the growth hormone receptor it has been shown to be equally potent to 22kDa. It appears that 20kDa has lower diabetogenic activity then 22kDa. The pituitary releases a blend of these two isoforms with 20kDa averaging perhaps 10% of the total although this percentage increases post-exercise. Currently there is no synthetic produced for external administration for this isoform.

Growth hormone (GH) in the body is released in pulsatile fashion. It has been demonstrated that this pattern promotes growth. The pituitary is capable of rather quickly synthesizing very large amounts of growth hormone which it stores large amounts in both a finished and unfinished form. Adults rarely experience GH pulses (i.e. releases of pituitary stores) that completely deplete these stores. As we age we do not lose the ability to create and store large amounts of growth hormone. Rather we experience a diminished capacity to "instruct" their release. The volume of GH that is released can not be properly equated to the exogenous administration of synthetic GH for the reason that a set of behavioral characteristics accompany natural GH that differ from those of synthetic GH. Among those characteristics are concentrated pulsatile release which upon binding in mass to growth hormone receptors on the surface of cells initiate signaling cascades which mediate growth events by translocating signaling proteins to the nucleus of the cell where protein transcription and metabolic events occur.

These very important signaling pathways desensitize to Growth Hormone's initiating effects and need to experience an absence of Growth Hormone in order to reset and be ready to act again. The presence of GH released in pulsatile fashion is graphed as a wave with the low or no growth hormone period graphed as a trough. Therefore attempting to find a natural GH to synthetic GH equivalency is not very productive because in the end what is probably import is:
- the quantity & quality of intracellular signaling events; and
- the degree to which GH stimulates autocrine/paracrine (locally produced/locally used) muscle IGF-1 & post-exercise its splice variant MGF.
Synthetic GH versus Natural GH in IUs

An attempt has been made on my part and can be found at:
Growth Hormone Administration vs. CJC-1295/GHRP-6 + GHRH


Units of Measurement

Growth Hormone (GH) like other biologically active substances is measured in International Units (abbreviated as IU) which are based on the measured biological activity for that substance the establishment of which is determined by international agreement. International Units are specific to each substance and so one IU of one substance has no equivalence to one IU of another substance.

While it is fairly straightforward to compare the amount of GH among various dosing administrations (a two (2) iu dose is twice the amount of a four (4) iu dose) and it is easy to ask the manufacture the weight of each iu (Nutropin reveals that 1 iu of their GH is equal to 333 mcg while Lilly's Humatrope trials define 1 iu as 370 mcg (2.7iu per 1mg)) it is not so simple to compare Growth Hormone to other "Growth Hormone Releasing" compounds such as CJC-1295 and GHRP-6.

Practically all studies that use Growth Hormone (GH) or CJC-1295/GHRP-6 + GHRH
(GHRH) or its analog CJC-1295 or Growth Hormone Releasing Peptides all take blood samples to measure the amount of GH present in blood plasma at various points in time. The unit of measurement is a standardized unit which can be used to make comparisons across different compounds.

The studies either report results as "nanograms (ng) per milliliter (ml)" or "micrograms (ug) per liter (L)". For the reason that ng = 1/1000 ug and ml = 1/1000 L, ng/ml will always equal ug/L. So no matter how the studies report results comparison is straightforward. In making the cross-comparisons contained herein for simplicity I have chosen to report results as ng/ml.

In addition the amount of hormone released into plasma (i.e. concentration) is based on units divided by time. This measurement is called area under the curve (AUC). However some studies will use the hour as the unit of time while others will use the minute. Therefore comparing AUCs between studies using different units of time requires a conversion to a common unit of time.

I will make the conversion herein in written form but be careful when you look at graphs.

Therefore this examination will look to several studies involving administration of the compounds of interest and compare the blood plasma levels of GH and peak concentration as a result of administration of each tested compound. The result of this cross-study examination will reveal the efficaciousness of various doses of GH, CJC-1295 and GHRH + GHRP-6 in increasing GH in blood plasma.
Studies used for comparison

Growth Hormone Administration

The primary study used herein is the Lilly Clinical trial using single dose administration of Humatrope in normal adults to assess pharmacokinetics. The doses used were .05 IU/kg (intravenously) and .27iu/kg (subcutaneously and intramuscular). In an 80kg adult that equates to 4iu and about 22iu. In our comparison we will only look at the 22iu subcutaneous and intramuscular dose.


CJC-1295 Administration

In "Prolonged Stimulation of Growth Hormone (GH) and Insulin-Like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults", Sam L. Teichman, et al. Journal of Clinical Endocrinology & Metabolism 91(3):799-805, sixty-six healthy normal men and women aged 21-61 were administered various doses of CJC-1295 (long-lasting GHRH analog). The CJC-1295 was administered in a single dose and again in some groups 7 days later and other groups 14 days later. For the reason that we are only examining a week's worth of data only the initial dose is of interest. Blood samples were collected before dosing and then at 15, 30, and 60 minutes and 2, 3, 4, 6, 8, 10, 12, and 24 hours afterdosing; and then every 8 hours on days 2–3, then daily on days 4, 5, 6, 7.

The doses administered were: 30mcg/kg; 60mcg/kg; 125mcg/kg; 250mcg/kg

GHRH + GHRP-6 Administration

While we are limited in our choice of GH administration studies and CJC-1295 studies (there are only two, the results of which are available to the public) we have many available studies measuring the effects of co-administration of GHRH and GHRPs.

So we will briefly look at the results from two studies to give us an idea of how much GH release is contributed by the enhanced pulse brought on by this synergistic combination.

They are, "Inhibition of growth hormone release after the combined administration of GHRH and GHRP-6 in patients with Cushing's syndrome", Alfonso Leal-Cerro, et al., Clinical Endocrinology 1994, 41 (5) , 649–654

and

"Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone", Bowers, C.Y., et al. J. Clin. Endocrinol. Metab. 70, 975–982.
What's Normal?

Before we look at the studies lets take a brief look at how much growth hormone (GH) is secreted naturally.

The following very comprehensive study measured growth hormone output over twenty-four hours among healthy normal people of all ages.


Age-Related Changes in Slow Wave Sleep and REM Sleep and Relationship With Growth Hormone and Cortisol Levels in Healthy Men, Eve Van Cauter, PhD; Rachel Leproult, MS; Laurence Plat, MD, JAMA. 2000; 284:861-868

The youngest category, those under 25 years of age secrete about 2iu of GH per 24 hours, while those in older categories sectrete 1 iu or less.

Note that Humatrope indicates that absolute bioavailability of an intramuscular or subcutaneous dose is about 66%. So perhaps 3iu of exogenously administered synthetic GH is a replacement dose equivalent to 2iu of indogenously secreted GH.

For most of the full study see: Post #558 - Age-Related Changes in Slow Wave Sleep and Relationship With Growth Hormone Levels

Comparing GH administration to CJC-1295 administration

Total GH Release:

When CJC-1295 was administered at 30mcg/kg; 60mcg/kg; 125mcg/kg and 250mcg/kg the total GH levels (area under the curve (AUC)) were respectively:

AUC: 758, 969, 977, and 1370 ng/ml per hour


Keep in mind that for a 80kg adult the 30mcg/kg dosing amounts to 2.4mgs of CJC-1295 per week and the 60mcg/kg dosing amounts to 4.8mgs of CJC-1295.

So 2.4 mgs of CJC-1295 produced an AUC of 758 ng/ml per hour.

When synthetic Growth Hormone (Humatrope) was administered at the equivalent of 22iu (in someone weighing 80+ kg) the following GH levels (area under the curve (AUC)) were reached:

AUC Intramuscular: 495 +/- 106

AUC Subcutaneous: 585 +/- 90

Peak Concentration:

However the GH release pattern results in a much higher mean maximum concentration for the GH administration than the CJC-1295 administration.

The GH study resulted in peaks of 53 to 63 ng/ml.

The CJC-1295 study resulted in dose respected peaks of 6.6; 9.6; 9.9; 13.3 ng/ml.

__________________

Comparing GH administration to GHRP + GHRH administration

Total GH Release:

The Alfonso Leal-Cerro study demonstrated the following GH release:
GHRH by itself dosed at 100mcg resulted in:
(AUC) 120 minutes = 1420 ± 330 ng/ml when we convert that to AUC measued in hours we get about: 25 ng/ml

GHRP-6 by itself dosed at 100mcg resulted in:
(AUC) 120 minutes = 2278 ± 290 ng/ml when we convert that to AUC measued in hours we get about: 40 ng/ml

GHRH + GHRP-6 dosed together at 100mcg each resulted in:
(AUC) 120 minutes = 7332 ± 592 ng/ml when we convert that to AUC measued in hours we get about: 130 ng/ml
The Bowers study demonstrated that a small dose of GHRP (.1mcg/kg) added to a saturation dose of GHRH (1mcg/kg) resulted in the following GH release:
(AUC) 120 minutes = 10,065 ng/ml when we convert that to AUC measued in hours we get about: 170 ng/ml

In comparison to synthetic GH administration we find that:

22iu of synthetic GH results in 495 - 585 ng/ml
Saturation doses of GHRH & GHRP results in 130 - 170 ng/ml

These results indicate that 22iu is between 3.8 and 3.4 more efficacious then a single administration of GHRH & GHRP which means that a single dose of GHRH & GHRP has the potential to produce better then the equivalent of 5iu of GH in plasma.

A dosing protocol of GHRH + GHRP at saturation dose, administered 3 times per day has the potential to exceed the equivalent of 15iu.

Note though that using this methodology GHRP-6 at a saturation dose by itself may add the equivalent of 1.4 to 1.8 iu per administration... or 4.2 to 5.4 iu per day if administered three times.


Peak Concentration:

From the graphs it is easy to see that GHRH+GHRP results in short-term peaks of 80 to 130 ng/ml.

While the synthetic GH study resulted in less pronounced peaks of 53 to 63 ng/ml of longer duration.

Systemic IGF-1 levels

Simply stated the synthetic Growth Hormone when administered intramuscularly or subcutaneously in high enough dose results in a release profile that is not pulsatile. The release profile is an elevation and this elevation results in higher levels of systemic IGF-1 in circulation then either an intravenous administration of GH or administration of the pulsatile peptides.

While multiple daily dosings of GHRH/GHRP result in a significant rise in systemic IGF-1 (not graphed out here) they do not over time result in as substantial an elevation of circulating IGF-1 as synthetic GH administered non-intravenously.

To understand the difference in GH in plasma profile of synthetic GH administered by intravenous I provide a copy of the GH study graph identical to the clinical study graph posted above with the addition of the intravenous dosing of GH. As you can see intravenous dosing of GH results in what could be described as a pulse because GH is elevated very high and then clears quickly.

So what does a high dose of synthetic GH administered subcutaneously or intramuscularly (but not by IV) do to systemic levels of IGF-1?

To find out we must switch to a Japanese study which undertook such study.

In Pharmacokinetics and Metabolic Effects of High-Dose Growth Hormone Administration in Healthy Adult Men, Toshiaki Tanaka, et al., Endocrine Journal 1999, 46 (4), 605-612, fifteen healthy normal Japanese adult males aged from 20 to 27 years were administered various doses of recombinant GH (Norditropin). The GH was administered in a single dose at 9:00 a.m. after overnight fasting. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 9, 12 and 24 hours after the single injection.

The doses administered were: .075iu/kg; .15iu/kg and .30iu/kg
When the average weight of each test subject is accounted for the doses administered approximated: 5iu; 10iu and 20iu

In the higher dose category the study dosed every day for a week and collected blood samples each day.

IGF-1 levels were measured and can be graphed as follows:


From this graph a few quick things can clearly be understood:

• IGF-1 creation is a slow ongoing process that increases every day that you administer GH until it plateaus after a week. This should tell you that there is no fear that anything will specifically interfere with GH's ability to instigate IGF-1 creation. All of the timing protocols which fear that insulin or "this and that" will interfere with IGF-1 creation are baseless and such "write-ups" that call for timing are flawed.

• It is constant GH elevations that result in ever higher levels of systemic IGF-1 creation

What none of this tells us

This does not tell us what is happening locally. By locally I mean IGF-1 that is not made in the liver and circulated systemically. Local IGFs are made in small amounts and used exclusively in the tissue of their birth.

Local IGF-1 in muscle has been demonstrated to be responsible for muscle growth and only if muscle-made IGF-1 is lacking does systemic IGF-1 play a significant (although incomplete) role.

Local IGFs in muscle are increased by growth hormone and testosterone. It is conjectured that pulsatile GH (such as IV dosing) or the use of GHRH/GHRPs results in high levels of muscle IGFs w/o creating high levels of systemic circulating IGFs.

If this proves to be true then that would be an advantage because high systemic levels of IGF-1 are positively correlated w/ cancer and mortality.

More detailed discussions about these sorts of things take place deeper in this thread.

Rather than demonstrate absolute values this comparison articles should serve to demonstrate that the body can produce pharmacological levels of growth hormone.

Brief overview of natural GH release

The initiation of growth hormone release in the pituitary is dependent on a trilogy of hormones:
Somatostatin which is the inhibitory hormone and responsible in large part for the creation of pulsation;

Growth Hormone Releasing Hormone (GHRH) which is the stimulatory hormone responsible for initiating GH release; and

Ghrelin which is a modulating hormone and in essence optimizes the balance between the "on" hormone & the "off" hormone. Before Ghrelin was discovered the synthetic growth hormone releasing peptides (GHRPs) were created and are superior to Ghrelin in that they do not share Ghrelin's lipogenic behavior. These GHRPs are GHRP-6, GHRP-2, Hexarelin and later Ipamorelin all of which behave in similar fashion.
In the aging adult these Ghrelin-mimetics or the GHRPs restore a more youthful ability to release GH from the pituitary as they turn down somatostatin's negative influence which becomes stronger as we age and turn up growth hormone releasing hormone's influence which becomes weaker as we age.

The exogenous administration of Growth Hormone Releasing Hormone (GHRH) creates a pulse of GH release which will be small if administered during a natural GH trough and higher if administered during a rising natural GH wave.

Growth Hormone Releasing Peptides (GHRP-6, GHRP-2, Hexarelin) are capable of creating a larger pulse of GH on their own then GHRH and they do this with much more consistency and predictability without regard to whether a natural wave or trough of GH is currently taking place.

Synergy of GHRH + GHRP

It is well documented and established that the concurrent administration of Growth Hormone Releasing Hormone (GHRH) and a Growth Hormone Releasing Peptide (GHRP-6, GHRP-2 or Hexarelin) results in synergistic release of GH from pituitary stores. In other words if GHRH contributes a GH amount quantified as the number 2 and GHRPs contributed a GH amount quantified as the number 4 the total GH release is not additive (i.e. 2 + 4 = 6). Rather the whole is greater than the sum of the parts such that 2 + 4 = 10.

While the GHRPs (GHRP-6, GHRP-2 and Hexarelin) come in only one half-life form and are capable of generating a GH pulse that lasts a couple of hours re-administration of a GHRP is required to effect additional pulses.

Growth Hormone Releasing Hormone (GHRH) however is currently available in several forms which vary only by their half-lives. Naturally occurring GHRH is either a 40 or 44 amino acid peptide with the bioactive portion residing in the first 29 amino acids. This shortened peptide identical in behavior and half-life to that of GHRH is called Growth Hormone Releasing Factor and is abbreviated as GRF(1-29).

GRF(1-29) is produced and sold as a drug called Sermorelin. It has a short-half life measured in minutes. If you prefer analogies think of this as a Testosterone Suspension (i.e. unestered).

To increase the stability and half-life of GRF(1-29) four amino acid changes where made to its structure. These changes increase the half-life beyond 30 minutes which is more than sufficient to exert a sustained effect which will maximize a GH pulse. This form is often called tetrasubstituted GRF(1-29) (or modified) and unfortunately & confusingly mislabeled as CJC-1295. If you prefer analogies think of this as a Testosterone Propionate (i.e. short-estered).

Note that some may also refer to this as CJC-1295 without the DAC (Drug Affinity Complex).

Frequent dosing of either the aforementioned modified GRF(1-29) or regular GRF(1-29) is required and as previously indicated works synergistically with a GHRP.

In an attempt to create a more convenient long-lasting GHRH, a compound known as CJC-1295 was created. This compound is identical to the aforementioned modified GRF(1-29) with the addition of the amino acid Lysine which links to a non-peptide molecule known as a "Drug Affinity Complex (DAC)". This complex allows GRF(1-29) to bind to albumin post-injection in plasma and extends its half-life to that of days. If you prefer analogies think of this as a Testosterone Cypionate (i.e. long-estered). However this is not accurate. CJC-1295 results in continual GH bleed. Although natural pulsation still occurs CJC-1295 does nothing to increase those pulses. Instead it raises base levels of GH and creates a more feminized pattern of release. This not desirable.

Modified GRF(1-29)however when combined with a GHRP brings about a substantial pulse which has desirable effects.

What follows on this first page of the thread is:
- A Basic Peptide Primer (which introduces the concept & structure of peptides)

- A Brief Summary of Dosing and Administration (for someone that wants to know the "how to use" straight away)
If all of this is a bit unclear because a lot of new concepts are thrown at you one of my original very thorough articles is available:
Post #5 - Basic Guide: Growth Hormone Secretagogues     brid  ช่วยย้ายที่อยู่-วางของข้อมูล มาฝากใน webเราได้ไหม

Post #6 - Basic Guide: Growth Hormone Secretagogues (part II) brid  ช่วยย้ายที่อยู่-วางของข้อมูล มาฝากใน webเราได้ไหมไม่ยากโชว์ว่าอยู่ในwebของคนอื่น

I have only one pet-peeve and that is when someone refers to synthetic growth hormone as "real" growth hormone. The GH that your body produces is as real as it gets. It is what grew you from a fetus to a boy (girl) and from a boy (girl) to a man (woman). - DatBtrue

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ ~~~~~~~~~~~~~~~~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Basic Peptide Primer
Written by Datbtrue
What is a peptide?

Peptides (proteins) are present in every living cell and possess a variety of biochemical activities. Some peptides are synthesized in the ribosomes of a cell by translation of mRNA (messenger RNA) into hormones and signaling molecules for example. Other peptides are assembled (rather then synthesized) and become enzymes with a vast variety of functions. Peptides also make up the structure of receptors which await binding of hormones & signaling molecules.

A peptide is a molecule created by joining two or more amino acids. In general if the number of amino acids is less than fifty, these molecules are called peptides, while larger sequences are referred to as proteins.

So peptides can be thought of as tiny proteins. They are merely strings of amino acids.

Raw Constituents of Peptides (Amino Acids)

Amino acids are small molecules made up of atoms. As part of their structure they posses a grouping of a Nitrogen (N) atom bonded to two Hydrogen (H) atoms. This is called an amino group and written as (NH2). In addition their structure is also made up of a second grouping of a Carbon (C) atom bonded to two Oxygen (O) and one Hydrogen atom. This group is called a carboxyl group and is written as (COOH).

Between these two groupings are atoms and bonds unique to each amino acid. In other words all amino acids possess the two groupings (amino & carboxyl) as end-points between which are sandwiched a unique set of atoms.

Amino Acids

Inside the human body there are twenty standard amino acids used by cells in peptide biosynthesis (i.e. the cellular creation of peptides from amino acids). Our genetic code specifies how to synthesize peptides and proteins from these amino acids.

Amino acids are classified into two groups: essential amino acids and nonessential amino acids.

An essential amino acid is an indispensable amino acid which cannot be made by the body and must be supplied by food. These include isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Another amino acid - histidine is considered semi-essential because the body does not always require dietary sources of it.

Nonessential amino acids are made by the body from the essential amino acids or the routine breakdown of proteins. The nonessential amino acids are arginine, alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, proline, serine, and tyrosine.

All twenty amino acids are equally important in maintaining a healthy body. They are the raw constituents of peptides and proteins.

The standard abbreviations for amino acids come in two forms: a one letter form and a three letter form. They are:

A - Ala - Alanine
C - Cys - Cysteine
D - Asp - Aspartic Acid
E - Glu - Glutamic Acid
F - Phe - Phenylalanine
G - Gly - Glycine
H - His - Histidine
I - Ile - Isoleucine
K - Lys - Lysine
L - Leu - Leucine
M - Met - Methionine
N - Asn - Asparagine
P - Pro - Proline
Q - Gln - Glutamine
R - Arg - Arginine
S - Ser - Serine
T - Thr - Threonine
V - Val - Valine
W - Trp - Tryptophan
Y - Tyr - Tyrosine


Amino acids exist in either D (dextro) or L (levo) form. Most of the amino acids found in nature (and all within human cells) are of the L-form. As a generality all amino acids except glycine have a mirror image of the L-form. This mirror image is called the D-form. It is common when referring to the L-form (naturally occurring form) to leave off the "L" designation whereas the "D" designation is always explicitly written.

D-amino acids are found naturally in bacterial cell walls and used in some synthetic peptides to make a peptide more stable or more resistant to degradation.

Amino Acid + Amino Acid = Peptide

The amino acids are joined together by what is known as a "peptide bond". A "peptide bond" is a linkage in which the nitrogen atom of one amino acid (from the amino group (NH2) binds to the carbon atom of another amino acid's carboxyl group (COOH).

During this binding process a molecule of water is released. This is called a condensation reaction.

The resulting CO-NH bond is called a peptide bond, and the resulting molecule is called an amide.

On the following image note that the COOH group gives up an Oxygen Hydrogen (OH) bond and the NH2 group gives up a Hydrogen (H). This forms H2O, which is a water molecule which is not part of the newly created peptide. NOTE: in the following image the C (carbon) symbol is missing as it is assumed so I indicate it with a blue square.

T

This reaction creating a peptide bond between two amino acids creates a peptide. We can call this peptide (made up of two amino acids) a dipeptide.

This process can be repeated using the twenty amino acids as raw material to create longer peptide chains. Sometimes peptide chains consisting of fifty to 100 amino acids are called polypeptides. Often a peptide chain beyond 100 amino acids is called a protein.

GHRP-6 is a peptide made up of just six amino acids. It's structure is often written as His-DTrp-Ala-Trp-DPhe-Lys-NH2

Note that the Carboxyl grouping (COOH) is assumed in the first position and is usually not written. The amino group (NH2) is wrtitten in the last position. The "meat" or the part that makes GHRP-6 distinct is the seqence in the middle of histadine bonded to the "D" form of Tryptophan bonded to Alanine bonded to Tryptophan bonded to the "D" form of Phenylalanine bonded to Lysine.

Pepdide bonds are formed by water (H2O) condensation (removing water). The converse is also true. A peptide bond can be broken down by hydrolysis (adding water).

The Amino Acid Structures of Peptides discussed in this thread

Growth Hormone Releasing peptides (GHRPs) (GH pulse initiators):
- GHRP-6 (His-DTrp-Ala-Trp-DPhe-Lys-NH2)

- GHRP-2 (DAla-D-2-Nal-Ala-Trp-DPhe-Lys-NH2)

- Hexarelin (His-D-2-methyl-Trp-Ala-Trp-DPhe-Lys-NH2)

- Ipamorelin (Aib-His-D-2-Nal-DPhe-Lys-NH2) - Ref-1
NOTES:
Aib = Aminoisobutyryc acid
D-2-Nal = "D" form of 2’-naphthylalanine
Growth Hormone Releasing Hormone (GHRH) (amplifies the GHRP initiated pulse):
- Growth Hormone Releasing Hormone (GHRH) aka GRF(1-44) (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile- Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly- Ala-Arg-Ala-Arg-Leu-NH2) = half-life "less then 10 minutes", perhaps as low as 5 minutes. - Ref-2


- GRF(1-29) aka Sermorelin (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val- Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile -Met-Ser-Arg-NH2) - the biologically active portion of the 44 amino acid GHRH = half-life "less then 10 minutes", perhaps as low as 5 minutes. - Ref-3
- Longer-lasting analogs of GRF(1-29):
-- replace the 2nd amino acid Alanine w/ D-Alanine only to modify GRF(1-29), D-Ala2 GRF(1-29) (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys- Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp -Ile-Met-Ser-Arg-NH2) = half-life "closer to 10 minutes" - Ref-4


-- replace the 2nd, 8th, 15th & 27th amino acids & get modified GRF(1-29) or CJC-1295 w/o the DAC (i.e. the part that will bind to albumin & make the half-life days) (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys- Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln- Asp-Ile-Leu-Ser-Arg-NH2) = Half-life at least 30 minutes or so - Ref-5

-- CJC-1295 (Tyr-DAla-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys- Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu- Gln-Asp-Ile-Leu-Ser-Arg-Lys-(Maleimidopropionyl)- NH2) = Half-life measured in days, - Ref-6
NOTES:
Lys = linker to the Drug Affinity Complex (aka (Maleimidopropionyl))
"Since GH is released in a pulsatile manner and a higher level of GH is observed between 15 and 30 min after subcutaneous administration of GH-RH analogues, hydrolysis by trypsin-like enzymes could not affect the result of stimulation." - Potent Trypsin-resistant hGH-RH Analogues, JAN IZDEBSKI, J. Peptide Sci. 10: 524–529 (2004)
The analog in the above quoted study resisted degradation for 30 minutes. The quote implies that if your analog can last 30 minutes it has tapped out the potential for a single pulse.

Since another pulse won't be generated for about 2.5 - 3 hours analogs that last more than 30 minutes up to 3 hours are not any more beneficial.

You would need an analog that kept growth hormone releasing hormone around beyond 3 hours to have it trigger a second pulse.

Otherwise dosing the 30 minute analog every 3 hours will maximize GH output OR you could just use an analog such as CJC-1295 which lasts for many days and will trigger several GH pulses a day for several days on a single dose.
References:

Ref-1 - "lack of effect on ACTH and cortisol plasma levels" - Ipamorelin, the first selective growth hormone secretagogue , K Raun, European Journal of Endocrinology, 1996 Vol 139, Issue 5, 552-561

Ref-2 - Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus, Frohman LA, J Clin Invest. 1986 78:906–913 and Incorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

Ref-3 - Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus, Frohman LA, J Clin Invest. 1986 78:906–913 and Incorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

Ref-4 - Incorporation of D-Ala2 in Growth Hormone-Releasing Hormone-( l-29)-NH2 Increases the Half-Life and Decreases Metabolic Clearance in Normal Men, STEVEN SOULE, Journal of Clinical Endocrinology and Metabolism 1994 Vol. 79, No. 4

Ref-5 - See: Posts within this thread

Ref-6 - See: Posts within this thread
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A Brief Summary of Dosing and Administration

Dosing GHRPs

The saturation dose in most studies on the GHRPs (GHRP-6, GHRP-2, Ipamorelin & Hexarelin) is defined as either 100mcg or 1mcg/kg.

What that means is that 100mcg will saturate the receptors fully, but if you add another 100mcg to that dose only 50% of that portion will be effective. If you add an additional 100mcg to that dose only about 25% will be effective. Perhaps a final 100mcg might add a little something to GH release but that is it.

So 100mcg is the saturation dose and you could add more up to 300 to 400mcg and get a little more effect.

A 500mcg dose will not be more effective then a 400mcg, perhaps not even more effective then 300mcg.

The additional problems are desensitization & cortisol/prolactin side-effects.
Ipamorelin is about as efficacious as GHRP-6 in causing GH release but even at higher dose (above 100mcg) it does not create prolactin or cortisol.

GHRP-6 at the saturation dose 100mcg does not really increase prolactin & cortisol but may do so slightly at higher doses. This rise is still within the normal range.

GHRP-2 is a little more efficacious then GHRP-6 at causing GH release but at the saturation dose or higher may produce a slight to moderate increase in prolactin & cortisol. This rise is still within the normal range although doses of 200 - 400mcg might make it the high end of the normal range.

Hexarelin is the most efficacious of all of the GHRPs at causing an increase in GH release. However it has the highest potential to also increase cortisol & prolactin. This rise will occur even at the 100mcg saturation dose. This rise will reach the higher levels of what is defined as normal.
Desensitization
GHRP-6 can be used at saturation dose (100mcg) three or four times a day without risk of desensitization.

GHRP-2 probably at saturation dose several times a day will not result in desensitization.

Hexarelin has been shown to bring about desensitization but in a long-term study the pituitary recovered its sensitivity so that there was not long-term loss of sensitivity at saturation dose. However dosing Hexarelin even at 100mcg three times a day will likely lead to some down regulation within 14 days.
If desensitization were to ever occur for any of these GHRPs simply stopping use for several days will remedy this effect.

Chronic use of GHRP-6 at 100mcg dosed several times a day every day will not cause pituitary problems, nor significant prolactin or cortisol problems, nor desensitize.

GHRH

Now Sermorelin, GHRH (1-44) and GRF(1-29) all are basically GHRH and have a short half-life in plasma because of quick cleavage between the 2nd & 3rd amino acid. This is no worry naturally because this hormone is secreted from the hypothalamus and travels a short distance to the underlying anterior pituitary and is not really subject to enzymatic cleavage. The release from the hypothalamus and binding to somatotrophs (pituitary cells) happens quickly.

However when injected into the body it must circulate before finding its way to the pituitary and so within 3 minutes it is already being degraded.

That is why GHRH in the above forms must be dosed high to get an effect.

GHRH analogs

All GHRH analogs swap Alanine at the 2nd position for D-Alanine which makes the peptide resistant to quick cleavage at that position. This means analogs will be more effective when injected at smaller dosing.

The analog tetra or 4 substituted GRF(1-29) sometimes called CJC w/o the DAC or referred to by me as modified GRF(1-29) has other amino acid modifications. They are a glutamine (Gln or Q) at the 8-position, alanine (Ala or A) at the 15-position, and a leucine (Leu or L) at the 27-position.

The alanine at the 8th position enhances bioavailability but the other two amino substitutions are made to enhance the manufacturing process (i.e. create manufacturing stability).

For use in vivo, in humans, the GHRH analog known as CJC w/o the DAC or tetra (4) substituted GRF(1-29) or modified GRF(1-29) is a very effective peptide with a half-life probably 30+ minutes.

That is long enough to be completely effective.

The saturation dose is also defined as 100mcg.

Problem w/ Using any GHRH alone

The problem with using a GHRH even the stronger analogs is that they are only highly effective when somatostatin is low (the GH inhibiting hormone). So if you unluckily administer in a trough (or when a GH pulse is not naturally occurring) you will add very little GH release. If however you luckily administer during a rising wave or GH pulse (somatostatin will not be active at this point) you will add to GH release.

Solution is GHRP + GHRH analog

The solution is simple and highly effective. You administer a GHRH analog with a GHRP. The GHRP creates a pulse of GH. It does this through several mechanisms. One mechanism is the reduction of somatostatin release from the hypothalamus, another is a reduction of somatostatin influence at the pituitary, still another is increased release of GHRH from the brain and finally GHRPs act on the same pituitary cells (somatotrophs) as do GHRHs but use a different mechanism to increase cAMP formation which will further cause GH release from somatotroph stores.

GHRH also has a way of reciprocally reinforcing GHRPs action.

The result is a synergistic GH release.

The GH is not additive it is synergistic. By that I mean:
If GHRH by itself will cause a GH release valued at 2
and GHRP itself will cause a GH release valued at 5

Together the GH is not 7 (5+2) it turns out to say 16!
A solid protocol

A solid protocol would be to use a GHRP + a GHRH analog pre-bed (to support the nightime pulse) and once or twice throughout the day.

For anti-aging, deep restful restorative sleep, the once at night dosing is all you need. For an adult aged 40+ it is enough to restore GH to youthful levels.

However for bodybuilding or fatloss or injury repair multiple dosings can be effective.

The GHRH analog can be used at 100mcg and as high as you want without problems.

The GHRP-6 can always be used at 100mcg w/o problems but a dose of 200mcg will probably be fine as well.

Again desensitization is something to keep an eye on particularly with the highest doses of GHRP-2 and all doses of Hexarelin.
So 100 - 200mcg of GHRP-6 + 100 - 500mcg+ of a GHRH analog taken together will be effective.
This may be dosed several times a day to be highly effective.
A solid approach is a bit more conservative at 100mcg of GHRP-6 + 100mcg of a GHRH analog dosed either once, twice, three or four times a day.
When dosing multiple times a day at least 3 hours should separate the administrations.

The difference is once a day dosing pre-bed will give a youthful restorative amount of GH while multiple dosing and or higher levels will give higher GH & IGF-1 levels when coupled with diet & exercise will lead to muscle gain & fatloss.

Dose w/o food

Administration should ideally be done on either an empty stomach or with only protein in the stomach. Fats & carbs blunt GH release. So administer the peptides and wait about 20 minutes (no more then 30 but no less then 15 minutes) to eat. AT that point the GH pulse has about hit the peak and you can eat what you want.

What do I get when I order Kefei?
Kefei box contains either 10 vials with 10 iu in each total 100 iu per box or 10 vials with 4 iu in each total 40 iu per box.

What type of syringes do I need and where can I get them?
To inject Kefei HGH, you need Insulin syringes. We recommend the standard 1ml U-100 30G Insulin syringes. To reconstitute it you can use 2-2.5ml syringe with attached needle of about 19-23G.Syringes can usually be purchased over-the-counter without prescription.

How do I turn Kefei into an injectable solution?
Mix Kefei HGH with a solvent such as sterile water or bacteriostatic water, a process known as reconstitution. It is only after you mix it with the solvent that it becomes a clear solution you can inject. This process shouldn't take more than a few minutes.

Where can I get sterile or bacteriostatic water?

You can try you local pharmacy as it may not require a prescription in your country. Most people get sterile water and bacteriostatic over the internet. Just run a google search for Bacteriostatic Water. You should get plenty of sites offering it. Prices are very low. Make sure the water you get reads "for injection" on the vial.

What is the difference between sterile and bacteriostatic water?
You can use either, the difference is for how long the HGH solution will remain potent. Reconstituted with Bacteriostatic Water for Injection (also known as Sterile Water with 0.9% benzyl alcohol) - A Kefei vial should be used within 10 days. Reconstituted with Sterile Water for Injection - A Kefei vial should be used within 3 days.

How much solvent do I need?

Kefei box contains either 40 iu (10*4iu) or 100 iu (10*10iu) 1 ml water is generally needed for both the 4 iu or the 10 iu vials, but its not critical, which means that if you have a little more or less water in the powdered HGH vial it does not decrease the effectiveness of the product.

How much HGH should I use?

These are the typical HGH doses that people use:

Anti-Aging: 2iu-4iu daily
Fat loss: 4iu-8iu daily
Muscle building: 8iu-24iu daily

* Most people follow one of the following protocols:
- Every day injections
- Every day injections, with 2 days off every 6th day (a.k.a. 5 days on, 2 days off)
- Alternate day injections - In this manner the dose taken every other day is double that of the "Every day injection" protocol.

Your doctor will determine the best protocol for you.

VERY IMPORTANT - WE ARE NOT DOCTORS AND WE DO NOT PROVIDE ANY KIND OF MEDICAL CONSULTATION OR LICENSED TO ADVICE ANYONE ABOUT THE USE OF HGH. YOU SHOULD ONLY USE KEFEI OR ANY HGH PRODUCT UNDER THE CARE OF A LICENSED PHYSICIAN. ONLY ADMINISTER THE HGH DOSE THAT YOUR DOCTOR PRESCRIBED YOU.

How can Kefei stay un-refrigerated during shipping ?

KeiFfei HGH is formulated specifically to withstand being out of refrigeration for 21 days without getting ruined. It's just important to place it in the refrigerator once you receive it and avoid exposure to light, heat or extreme temperatures. Simply store in the fridge 2-8 Deg C as soon as you get it.

What are the known side effects? 

Because prescription injections are so strong (more than your body naturally makes), your body's own natural mechanisms for making it and its secondary productions like IGF-1, your body might essentially say "I have plenty, there's no need to make it anymore", and shut down natural production. So it should be taken only with a doctor's advice or supervision (requires a prescription anyway). 

How to Use Peptides ?

Dosage for IGF and MGF

IGF1 L3 every second day, 40mcg until 70mcg. with a small dose start over every month and increase by 10mcg for muscle building. for fat loosing every day 50mcg one month and then one month break and again the same,one month "on" one "off".

MGF must you use 200mcg in the muscel each daY !!!! left/right (bizeps/trizeps) , on training day after the training and on days where is noch training in the afternoon !!!

Normally, one months usage dose will be about 15vials IGF-1 and 5vials MGF.

Facts about CJ1295 

The long half life of CJC-1295 is what makes it, potentially, so much more useful of a treatment for hor mone therapy as opposed to other GHRH products. Tests have been done to measure its effects upon hor mone levels based on various sized injections at specific intervals. Effects of CJC-1295 in one study were shown to have an effect for up to six days after the initial injection on increasing the amount of GH in the body. Some suggest that it may be possible to have effective treatments with this hor mone booster that only require you to have an injection once or twice a week, which is much more preferable to many people due simply to the ease of scheduling and for less injections overall, which, despite their obvious benefits, many people understandably do not enjoy. 

Important Info about Melanotan 2 

Melanotan2 is taken in a loading phase between .2mg daily up to .5mg twice a day. After using 1 vial most people are ready to start to get a little sun and from then on tan easily. After that to maintain a tan you only need about .2-.5mg a week but most take more. Side effects for a man is it makes you very horny. It also protects the skin from sun damage. Builds collagen too. Some people may get a negative side effect of nausea and facial flushing after taking the shot but not everyone does as I don't yet it still works great as I -owner of site- am tan without the sun:)

HCG used for Weight loss

A controversial usage of hCG is as an adjunct to the British endocrinologist Dr. A.T.W. Simeons' ultra-low-calorie weight-loss diet. Simeons, while studying pregnant women in India on a calorie-deficient diet, and fat boys with pituitary problems treated with low-dose hCG, discovered that both lost fat rather than lean (muscle) tissue. He reasoned that hCG must be programming the hypothalamus to do this in the former cases in order to protect the developing fitus, and proceeded to use low-dose daily hCG injections (125 mg) in combination with a customized ultra-low-calorie (500 cal/day, high-protein, low-carbohydrate/fat) diet to help obese adults lose dramatic amounts of adipose tissue without loss of lean, at a Salvator Mundi International Hospital in Rome, Italy, clinic mainly for celebrities. After Simeons death, the diet started to spread to specialized centers and via popularization by such as the controversial popular author Kevin Trudeau (search for hCG in that article for more details).

The controversy proceeds from warnings by the Journal of the American Medical Association[ and the American Journal of Clinical Nutrition that hCG is not safe, indeed ineffective, as a weight-loss aid on its own; yet its usage as cited above to increase testosterone production contradicts this assertion, since much late-life male obesity is associated with estrogen dominance and deficient testosterone in the mis-named, so-called andropause. Furthermore, in the Simeons protocol, it is, as in any diet, the ultra-low-calorie component (caloric deficit) that results in weight loss, if the protocol is followed strictly. hCGs role is supposedly to trigger the hypothalamic lean-protection mechanisms Simeons thought he saw, thus promoting mobilization and consumption of abnormal, excessive adipose deposits, while protecting normal adipose and lean tissue from being consumed, with the assumption that these protective hypothalamic mechanisms exist in males as well as females, to be acted upon by hCG.


HCG used for bodybuilding

by Bill Roberts - hCG is provided as a glycoprotein powder to be diluted with water, and acts in the body like luteinizing hormone (LH), stimulating the testes to produce testosterone even when natural LH is not present or is deficient. It therefore is useful for maintaining testosterone production and/or testicle size during a steroid cycle. Use of this drug in the taper is rather counterproductive, since the resulting increased testosterone production is itself inhibitory to the hypothalamus and pituitary, delaying recovery. Thus, if this drug is used, it is preferably used during the cycle itself. A daily amount of 500 IU is generally sufficient, and in my opinion usage should not exceed 1000 IU per day.

Daily administration is superior to less frequent administration.

Doses over 1000 IU are noted for their tendency to cause or aggravate gynecomastia, and also act to desensitize the testicles to LH.

hCG may be injected intramuscularly, subcutaneously, or in a shallow injection about 1/4" deep with the needle going straight in. A 29 gauge insulin needle is recommended. Injection speed should be slow.

Some hCG products are diluted 5000 or even 10,000 IU per mL, while others are diluted 1000 IU per mL. So far as I know there is no need to make the preparation so dilute. Once mixed, the preparation should be refrigerated and used within a few weeks. The substance is also somewhat temperature sensitive before mixing and should not be exposed to excessive heat.

hCG does not correct the problem of  progressively-decreasing ejaculatory volume that is typical during a steroid cycle. So far as I know the only cure is to go off-cycle and use Clomid, but it is possible that human menopausal gonadotropin (hMG), a related drug which works analogously to follicle stimulating hormone (FSH) might be useful during a cycle to treat this problem. HMG supports spermatogenesis and is commonly used in conjunction with hCG to treat male fertility problems. (Consider use of HMG to maintain ejaculatory volume to be a strictly past-the-cutting-edge hypothesis: I have not yet had the opportunity to test the matter.)

The athlete who would otherwise fail a urinary ratio test because of low epitestosterone may find hCG useful in increasing epitestosterone and therefore improving this ratio. A 500 IU dose is sufficient, but on the other hand, hCG itself is also banned by the IOC and is readily detected in urine.

hCG can also useful for returning testosterone to normal levels should levels be low post-cycle, or, with care, to increase levels from normal to high normal. Titration of the dose, by measuring T levels and then adjusting the hCG dose accordingly, is recommended for long term use.

Somatropin: a natural substance with a wide range of benefits

• Reduce excess body fat, especially abdominal fat. (The reduction of abdominal fat is the single most profound effect of HGH replacement.)
• Increase muscle mass (and physical strength if combined with moderate exercise).
• Reduce wrinkling of the skin and some other effects of skin aging.
• Re-grow internal organs that have atrophied with age.
• Increase bone density.
• Strengthen the immune system.

An increase in lean body mass is thought to be important in HIV disease because the loss of lean body mass is the form of wasting most closely related to an increased risk of death.