Written by: M.M. a/k/a DatBtrue
Copyright 2009 by M.M. a/k/a DatBtrue
All rights reserved. No part of this article may be reproduced in any form without the written permission of the copyright owner.
Written May 6, 2009
Special thanks to Beefy for his assistance.
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 Growth Hormone Releasing Hormone (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
**broken link removed** 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.