I originally posted this on 8/17/08 on AM. It might be useful here:
xxxxx said:
Dat, I have some HGH Frags and was wondering what your thought on adding it while doing CJC/GHRP?
I've been looking into combining the two (i.e. CJC-1295/GHRP-6 & Tyr176-hGH(176-191)) and believe if you are in "weight loss" mode it would be very effective.
Growth Hormone-Fat Cycle (Brief Look):
The secretion of growth hormone (GH) and the mass and distribution of body fat are connected through a complex series of interactions. There is sufficient evidence that a growth hormone-fat cycle exists and that elements of this cycle may possess regulatory functions.
The essential elements of the cycle are:
(1) GH-deficient individuals are often obese and lose body fat when they are treated with GH; GH is lipolytic in vitro and causes an acute release of free fatty acids (FFA) when administered in vivo;
(2) Free fatty acids (FFAs) released from adipocytes are likely to be metabolized within nearby cells and can also enhance the activity of UCPs;
(3) Circulating FFA inhibit the pituitary release of GH by most secretagogues, including growth hormone releasing hormone, and
(4) The obese state is characterized by a defect in GH release which may be reversed by weight loss.
Reference: Gertner JM, Growth hormone actions on fat distribution and metabolism. Horm Res 38:41–43, 1992.
So the inhibiting effect that GH (or Frag) has on its own release via an increase in circulating fatty acids is something to keep an eye on.
So what is GH Frag?
From a lecture given by the scientists that discovered it:
Previous studies from our laboratory have identified that a carboxy-terminal fragment of the human growth hormone (hGH), hGH(177-191), is the lipolytic/anti-lipogenic domain of intact hGH. By targeting the key enzymes involved in lipid metabolism, hGH(177-191) is able to increase lipolysis, and decrease lipogenesis in adipose tissue, resulting in reduction of body weight gain in obese rodent models. In view of its significant clinical potential, the aim of our study is to develop the peptide into a drug for the treatment of human obesity. A series of peptide analogues of hGH(177-191) were designed, synthesized and studied for the structure-activity relationship.
Peptide analogues of hGH(177-191), were prepared using Fmoc-amino acids by usual solid phase synthesis. After cleavage and purification, the Cys(Acm)182,189-hGH peptides were cyclized by an one-step oxidation by excess iodine (4.5-folds) in an acetic acid–water solution (80/20, v/v) for 60 min at room temperature. A final RP-HPLC purification was conducted and structure of the products were confirmed by ESI-MS.
To evaluate biological activity of the peptides, their inhibitory effects on lipid synthesis was examined using the in vitro lipogenesis assay. Results indicated that the length and the disulfide bond of hGH(177-191) were crucial for it to retain biological activities. Truncated analogues with deletion from either N- or C-terminus showed dramatic loss in activity. Ala182-hGH(177-191), a linear analogue, is also less active. On the other hand, Tyr176-hGH(176-191), coded as AOD9604, demonstrated a 52.4% increase in the in vitro bioactivity. Further studies in animals with AOD9604 demonstrated its specific in vivo activity.
Long-term treatment of C57BL/6J (ob/ob) mice with AOD9604 (500 ug/kg/day) had a marked effect on reducing the body weight gain and total body triglyceride after chronic oral administration. No significant change in tibia bone length in animals was observed between the treated and control groups. Unlike the intact hGH, data indicated that AOD9604 had no effect on bone growth.
Preclinical toxicology of AOD9604 was successfully completed in late 2000 with no unfavorable side effect observed. - Development of a Human Growth Hormone Peptide Analogue AOD9604 into an Anti-Obesity Drug, Woei-Jia Jiang, Robert Gianello, Mark Heffernan, Esra Ogru, Roksan Libinaki and Frank Ng
Dosing
...my quick run through the material indicates that there is not much information on dosing. First it is not possible to extrapolate doses used on lab animals to humans so those studies are of limited value. Second the drug company trials which tested for safety used high doses (25mcg/kg to 100mcg/kg). Third the drug company does not care about subcutaneous administration, they want an oral drug so subsequent studies use the oral delivery system where gram level dosing is used.
But from the oral dosing clinical trial one interesting thing emerged... that is that they found 10grams to be equally effective to 20grams and furthermore they found 60grams to have ZERO effect.
That means that there is an upper limit to dosing at which point you not only will get no further benefit BUT ALL benefit is lost and it is as if you took nothing.
The clinical trials though show measurable weekly fatloss. In some cases 1kg per week. This compound is particularly effective in older people...much more than in younger 20-somethings.
I suspect you don't need to take as high a dose as the studies might indicate. I'm not sure even the patent holders yet know the optimal subcutaneous dose. From their patent filing:
"The peptide which is the active ingredient of the pharmaceutical composition of this aspect of the invention exhibits advantageous therapeutic activity in the treatment of obesity in an animal when administered in an amount appropriate to the particular case. For example, from about 0.5 μg to about 20 mg per kilogram of body weight per day may be administered. Dosage regimens may be adjusted to provide the optimum prophylactic or therapeutic response. For example, one or more divided doses may be administered daily, weekly, monthly or in other suitable time intervals or the dose may be proportionally reduced as indicated by the exigencies of the clinical situation."
0.5 μg/kg is .5mcg/kg which is just 50mcg for a 100kg man.
Is such a low dose optimal? Probably not...but you'd probably get a very minimal positive effect from it.
If you combine the fragment Tyr176-hGH(176-191) with CJC-1295/GHRP-6 you will almost undoubtedly increase the fatloss.
Anyway I'm very interested in this compound. If I were in fatloss mode I'd probably add the Tyr176-hGH(176-191) at 100mcg dosed 3 times a day to CJC-1295 (dosed once at night at 100mcg)/ GHRP-6 (dosed three times a day at 100mcg).
The reason to keep the GHRP-6 dosing frequent is that fatty-acids blunt but do not eliminate the GH releasing effect of GHRP-6 as they do with GHRH (of which CJC-1295 is a long-lasting analogue).