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Growth Hormone Administration vs. CJC-1295 and GHRP-6

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) 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.
Therefore this examination will look to several studies involving administration of the compounds of interest and compare the blood plasma levels of IGF-1 and both peaks and total amount of GH blood plasma levels 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 & IGF-1 in blood plasma.

Studies used for comparison

Growth Hormone Administration
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

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 (because no other study administered such high doses in normal men) 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. There is a large variability among age groups, gender, fitness level and among individuals within a single age group. So the best we can do is generalize. The charts below are derived from GH blood plasma data collected over a 24 hour period for a normal man, a normal man after a fast, a normal woman and a normal woman after a fast. All ages were mid-20s.
Note that the night-time GH pulse peak for a man was about 20 ng/ml (aprox. 85% of 24hr GH release normally occurs at night).

Total GH release was as follows:
Men (Fed): Area Under the Curve (AUC): 94 ng/ml per 24 hours
Men (Fasted): AUC: 274 ng/ml per 24 hours
Women (Fed): AUC: 168 ng/ml
Women (Fasted) AUC: 264 ng/ml per 24 hours

Comparing GH administration to CJC-1295 administration
It is difficult to compare based on the following GH release graphs so let's examine the numbers.

Total GH Release:
When GH was administered at 5iu, 10iu & 20iu the total GH levels (area under the curve (AUC)) were respectively:
AUC: 311.5; 836.9; 1778.5 ng/ml per 24 hours

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; 1370 ng/ml per hour

NOTE: This is per hour while the GH study is per 24 hours

So based on the total GH concentration in blood plasma the lowest dose of CJC-1295 on a per hour basis results in more than twice the 24 hour GH secretion level of a 5iu dose of GH.

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 dose respected peaks of 55.4; 93.8; 180 ng/ml

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

The graph indicates that for the GH study the bulk of the peak lasts about 12 hours followed by low levels of GH. As an aside clearly GH administration would be better if it were administered in at least two doses per day.

But even IF 5iu of GH were administered in the morning followed by 5iu twelve hours later the total amount of GH released would be less than a low dose of CJC-1295 (311.5 + 311.5 < 758 ng/ml). Furthermore the CJC-1295 was dosed just once in seven days while the GH would need to be dosed every one of those 7 days.

IGF-1 Levels:

CJC-1295 elevates IGF-1 within the first day or two where it stays elevated for seven days.
GH elevates IGF-1 levels immediately where it stays elevated throughout the rest of the day.
Both the GH & CJC-1295 studies demonstrated a dose dependent increase in elevated IGF-1 levels. The highest GH dose of 20iu resulted in a similar IGF-1 level as the highest CJC-1295 dose. The lowest GH dose of 5iu resulted in an IGF-1 level not much different then the lowest CJC-1295 dose.
Again the CJC-1295 elevated IGF-1 for seven days from a single administration while GH would likely need to be dosed everyday (perhaps every other day) to match CJC-1295's chronic elevation of IGF-1.

Can CJC-1295 plus GHRP-6 match GH adminstration's peaks?
Adding GHRPs to CJC-1295 three times a day can amplify peaks and greatly add to the total GH secretion level.
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
GHRP-6 by itself dosed at 100mcg resulted in: (AUC) 120 minutes = 2278 * 290 ng/ml
GHRH + GHRP-6 dosed together at 100mcg each resulted in: (AUC) 120 minutes = 7332 * 592 ng/ml
By adding GHRP-6 to CJC-1295 (long-lasting GHRH) it may be possible to add almost 6000 ng/ml of GH release at each GHRP-6 dosing. [Figure arrived at by taking synergy amount 7332 and subtracting GHRH's contribution of 1420]

But what about those peaks?

Clearly adding GHRP-6 has the effect of matching GH's peaking power as measured by amplitude. The difference is that GH results in big hills lasting up to 12 hours. This really amounts to an elevation rather than a pulse. GH does not mimic the physiological pulsatile release of GH that naturally occurs while GHRP-6 particularly in the presence of GHRH does result in such a natural pulse. These pulses last for about 2 hours. If dosed three times a day the result would be three 2-hour pulses each of which exceed GH's 5iu and 10iu elevations and approach GH's 20iu elevation.
However 6 hours total of peak for the CJC-1295/GHRP-6 combination would be half of the 12 hours total of peak for the GH.
I do not know if it matters. I do not know if these two different peaking characteristics would result in different effects concerning growth

In CONCLUSION, CJC-1295 appears to result in higher concentrations of GH in blood plasma than does GH administration. When CJC-1295 is combined with GHRP-6 the total GH release is exacerbated.
GH administration results in higher GH maximum concentration or peaks then CJC-1295 alone. However when CJC-1295 is combined with GHRP-6 the peaking amplitude exceeds the 5iu & 10iu GH doses and approaches the 20iu dose. GH administration's peaks however last for 12 hours while CJC-1296/GHRP-6 results in a natural 2 hour peak at each dosing (i.e. 6 hours total).
Both CJC-1295 and GH appear equally effective at elevating and sustaining IGF-1 levels

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