Peptides vs GH

[EasyEJL]

Since you mention MGF, I know your opinion on IGF-1, but don't recall what you've said on the value of MGF use.

 

[Blade_HST]

http://www.professionalmuscle.com/forums/showthread.php?p=487161#post487161

 

[EasyEJL]

Thanks!

actually i'm still a little confused as MGF acting like its IGF-1 sounds cool and all, but with DatBrute's opinion on effectiveness of injected IGF-1, does that mean that since MGF is acting like it that MGF has the same effectiveness?

 

[Wise Guy]

Sermorelin (unmodified GRF(1-29) is not effective unless it is dosed in mgs not mcgs. The half-life is measured in minutes.

Modifed GRF(1-29) has a half-life long enough to have a positive effect at low dose when administered into a rising GH pulse (either natural or GHRP-induced).

Dat,

I believe SWALE (Dr John), for his patients, is still using sermorelin as his GHRH (obviously he has no choice - legally, its the only one he can use), at 100mcg a night along with his GHRP.

What I can garner from your post is that it is, for the most part, ineffective at 100mcg. And to use it in mg, it would be a cost nightmare

Perhaps it is a matter of cost versus effectiveness.

One may feel that for 90 bucks a month the 100mcg of Sermorelin might be illicit enough of a synergistic effect with the GHRP to make it worth using.

Or perhaps not.

I wonder what SWALE is up too with this protocol.

I wonder if he is considering just ditching sermorelin all together and just using GHRP, until something more effective is available for legal use, such as modified GRF (1-29)

What is your opinion of ipamorelin?

How about secratropin?

And thank you for all your work. I have spent countless amounts of hours(actually days) and lost party time researching your work

 

[DatBtrue]

...

I kinda get caught between a rock & a hard place on this forum for the reason that it is a bodybuilding forum where people want maximum whatever.

Sermorelin is NOT worthless and it is not ineffective. If I have written that anywhere I overstated things.

Studies have used Sermorelin (which for all intents & purposes is just native GHRH) to great effect some for many months at a time. These studies have to overcome two problems of which they only seem to be aware of one.

Problem #1

The first problem is the half-life is under 10 minutes. The reason that it is difficult to give an exact number is that very quickly within say 3 minutes enzymes begin to cleave the peptide between the 2nd & 3rd position, but the rest of the chain remains in tact. Assays that are not supersensitive continue to measure the remaining chain (aminos 3-29 or if full GHRH were used 3-44) as if it were the intact peptide.

I have seen it stated that once cleaved the remainder (3-29) has no biological value as concerns GH release & and I have seen it stated that it has weak value. I believe the latter that it has weak value that could become noticeable at higher doses.

The short-half life doesn't normally matter in our bodies when it is made in the hypothalamus and travels a short distance to the anterior pituitary right below. I doubt any cleavage takes place and full ligand binding takes place.

But when injected into plasma (whether subcutaneously or IV) the peptide is subjected to ezymatic cleavage.

"Although the therapeutic usefulness of hGHRH and its shorter analogue has been demonstrated, susceptibility to enzyme cleavage limits their use as effective drugs. It has been demonstrated that degradation at the site of injection after subcutaneous administration is extremely rapid. The estimated amount in the circulation after subcutaneous injection was only 4% of that obtained after intravenous administration. There is a great demand for more stable analogues which would allow a reduction in the doses and frequency of administration. Numerous analogues of hGH-RH have been synthesized and tested to obtain compounds of increased metabolic stability and potency." - New Potent hGH-RH Analogues with Increased Resistance to Enzymatic Degradation, Jan Izdebski, J. Peptide Sci. 8: 289–296 (2002)​

So to overcome this, the studies only using GHRH in a non-altered form (i.e. Sermorelin) used higher doses. One study used 1mg while another used 2mg daily amounts of the hormone. Another study used those high amounts but dosed twice a day while another three times a day.

So very positive results as measured by body composition changes and the like occurred in normal (usually older people) over the course of months with mg dosing broken into multiple doses subcutaneously each day.

Problem #2

The second problem seems to never have been addressed.

That problem, is that when you administer Sermorelin is important. If you administer it by itself when a natural pulse is occurring, especially if you time it to coincide with a rising wave then the Sermorelin is used and the effects very noticeable. But if you administer during a trough (or lack of a pulse) then the effects are almost negligible.

So that is one of the reasons results are said to be inconsistent or less predictable. It is not possible to wave time...

...except we do know a wave will come immediately PWO (post-exercise) and we do know that one will come soon after we drop off to sleep.

If you keep throwing darts at the wall, but the dart board only shows up at three hour intervals, how do you envision the end results? A lot of people with medical degrees overlook this simple point ...one of the reasons they can be dismissive.

One final point... we understand pulsation, waves & troughs. We understand on & off water faucets and we understand that it is the off faucet, somatostatin that is active during the troughs (or time periods when the pulse is suppressed). So we understand... and we can envision that in the face of somatostatin IF you blast the on faucet (which is Sermorelin (aka GHRH), the positive GH releaser) you may overcome somatostatin influence and create a pulse.

From these things we also understand that to concurrently inhibit somatoststin during Sermorelin would be a beneficial activity. So we would look to those things that do that effectively, such as Arginine.

Using both Sermorelin (GHRH) & a GHRP

Even the most casual reader of my thread at this point understands that Growth Hormone Releasing Peptides (GHRP-2, GHRP-6, Hexarelin & Ipamorelin) when administered always create GH pulses in normal people (with sex and age as no barrier). The specific details of which will not be recounted here but I will reiterate that they inhibit somatostatin in several ways and they increase natural release of GHRH & supplement its GH releasing ability when it binds to somatotrophs (i.e. pituitary cells capable of releasing GH).

With a GHRP there is no need to wait until a natural GH pulse occurs, you can with a single limitation effect one whenever you administer a GHRP such as GHRP-6. That limitation is simply "reload" or the restocking of GH stores in the pituitary cells. This happens rapidly, in part because those stores are made up of nearly finished GH and fragments, which can be made ready within the time period needed to engender a pulse every three hours. The finished product comes in two forms - 191 amino acid chain GH & a 176 amino acid chain both equally anabolic.

Almost all of the studies that administer a GHRP w/ a GHRH use Sermorelin. Often the pharmaceutical name is not used and the nomenclature GRF(1-29) is used. This means "Growth Hormone Releasing Fragment, amino acids 1 through 29". This IS native GHRH which is 44 amino acids long with the 15 amino acids that have no biological value eliminated.

So if you have read my thread and all of my blah, blah, blah, synergy, blah, blah, look how smart Dat is, blah, blah, blah... everytime I referred to a study demonstrating synergy between GHRP-6 (or other GHRP) and GHRH (aka GRF(1-29)) they were using the equivalent of Sermorelin.

These studies were not using any modified version of GRF(1-29).

Here is an example from one of my favorite studies, Preserved Growth Hormone (GH) Secretion in Aged and Very Old Subjects after Testing with the Combined Stimulus GH-Releasing Hormone plus GH-Releasing Hexapeptide-6, Dragan Micic, Journal of Clinical Endocrinology and Metabolism 1998 Vol. 83, No. 7

"As GH stimulant, it was administered the combined test of an iv bolus injection of 90 ug [mcg] GHRH (GRF 1–29 NH2, Geref Serono Laboratories, Madrid, Spain), immediately followed by an iv bolus injection of GHRP-6 (His-DTrp-Ala-Trp-DPhe-Lys-NH2; Peninsula Laboratories, Madrid, Spain), prepared as previously described." [90 mcg]​

Now Geref Serono holds the patent on GRF(1-29) and made the first FDA approved pharmaceutical drug of it and named it Sermorelin. It was primarily used for GH stimulation tests and was eventually sold to another pharmaceutical company which makes it available to the medical community as a prescription drug called Sermorelin.

Incidentally what kind of results did that study find?:

"...the combined administration of GHRH plus GHRP-6 (both at saturating dose) is nowadays considered the most potent stimulus of GH secretion in man (15), being able to restore the GH secretion in states associated with chronic blockade of somatotroph activity (as in obesity) (18). In the present work, the combined stimulus of GHRH-GHRP-6 has been studied in a group of very old subjects (age higher than 75 yr) showing no decline in the amount of GH secretion, as compared with both normal adults (less than 40 yr) and aged subjects (age 46–65 yr). A similar lack of age-related decline has been reported for normal subjects in their late adulthood (21). The GHRH-GHRP- 6-mediated GH discharge was similar for the three groups of age, with similar mean GH peaks, AUC, and secretory pattern, which suggests a very synchronized type of secretion."​

Other Comments that speak to what we are referring to here.

"Compared with GH, treatment with GH-secretagogues has several potential advantages. The moderating effect of insulin- like growth factor-I (IGF-I) feedback on the somatotroph could buffer against overtreatment. Unlike administered GH, GH secretion remains pulsatile during GHRH administration, presumably because of variability in endogenous secretion of somatostatin, although current GHRH treatment regimens do not take full advantage of this phenomenon because of the relatively short duration of action of sc GHRH injections." - Effects of Eight Months Treatment with Graded Doses of a Growth Hormone (GH)-Releasing Peptide in GH-Deficient Children, Vero Nica Mericq, Fernando Cassorla, Teresa Salazar, Alejandra Avila, German Iniguez, Cyril Y. Bowers, And George R. Merriam, Journal of Clinical Endocrinology and Metabolism 1998 Vol. 83, No. 7​

Incidentally that study ramped up dosages to 3mcg per kg over the study and only administered GHRH & GHRP-2 together in the final period. They found in GH defecient children:

"It is encouraging that growth velocities increased during treatment compared with before or after the treatment periods."​

...but also that GH release became desensitized to high dosing, although there were so many unknowns at the time of the study that they did not narrow this phenomena down to the single item of dose. We can do that today... I point this out because a quick read of the medical abstract by those that have better things to do then fully understand, will lead to "yes, but...not effective in the long run."

Here is an example of nightime release of GH from one of the children in the study- GHRP-2 versus GHRP-2 + GRF(1-29) aka Sermorelin:

​

So Sermorelin is effective but we can do better.

So if you read a post where I say use a modified form of Sermorelin (aka GRF(1-29)) it does not mean that Sermorelin is ineffective if used in a proper protocol which can be as low as 1mcg/kg.

However we have "off the label use" for altered forms of GRF(1-29) which allow us to achieve a larger effect. They do this because they are protected from quick enzymatic cleavage and thus have a longer half-life.

We also understand that there is no desensitization to GHRH so we can use any dose we want whereas with GHRPs we know (from discussion elsewhere (see my thread)) that we aren't going to experience desensitization w/ 100mcg of GHRP-6 dosing but may at say 300mcg dosing.

Back to Bodybuilding vs life usage

So back to my being between a rock and a hard place. There are a significant number of people that are older and read my thread & use these peptides for "better life" purposes. One gentleman & his wife use just 20mcgs of each. They are in an age bracket where that amount can make a difference and does. Not just a little but a LOT!!!! By a lot I mean the difference between crippling debilitating pain and relief.

On the other extreme a friend of mine has experimented with 4+ mgs (thats mgs NOT mcgs) of CJC-1295 (a long-acting form of GHRH) + 4+ mgs of GHRP-6 for periods of time on cycle and BOOM! He is a bodybuilder, doesn't mind the expense, doesn't mind all of the frequent administrations...

...he is a guy that can and has torn a Pec, had surgery, never lost size, even gained while he was active, healed quickly all by using a cocktail of growth factors injected into the wounded area. He is the ultimate guinea pig BUT building mass is important to him.

Between these two extremes you have the majority of people... and when I post sometimes it gets lost to whom I am speaking... but in general I am only posting science and references so others NEVER need to go by what I say and I conjecture an awful lot. I hope I make clear where I am conjecturing & my basis for it...

 

[EasyEJL]

So if you plan to use cjc1295 at a moderate dose anyhow - say 100mcg ED, is there any real benefit to using the cjc1295 with DAC vs the non-DAC version? And also given

The estimated amount in the circulation after subcutaneous injection was only 4% of that obtained after intravenous administration.

does it make sense to use cjc1295 IV?

 

[Wise Guy]

Thanks for that Dat. I really, really appreciate the work you do here.

It is beneficial for me, given that I am looking to start the GHRT protocol soon, if Dr. John gives it a go (I am a patient of his)

So your research in this area is important to me, given it is his inspiration as well.

I by no means am looking to body build.

I watched my grandparents age and pass and now my parents age and its quite heartbreaking

All I want is a little more out of my later years than they got.

 

[DatBtrue]

All I want is a little more out of my later years than they got.

Alternate day fasting.

 

[DatBtrue]

Thanks!

actually i'm still a little confused as MGF acting like its IGF-1 sounds cool and all, but with DatBrute's opinion on effectiveness of injected IGF-1, does that mean that since MGF is acting like it that MGF has the same effectiveness?

MGF may act as a better IGF-1 then IGF-1 LR3. It may bind to receptors with a stronger affinity.

IGF-1 LR3 has a lower binding affinity then native IGF-1 due to its alterations.

It is fact-based to say MGF is capable of binding to the IGF-1 receptor. It is conjecture based on people who dose sufficiently large amounts that it may act as a better IGF-1 then IGF-1 LR3.

 

[DatBtrue]

So if you plan to use cjc1295 at a moderate dose anyhow - say 100mcg ED, is there any real benefit to using the cjc1295 with DAC vs the non-DAC version?

I do not think so. In fact assuming equal purity levels, you will get more GRF(1-29) in 100mcg then you will in 100mcg of CJC-1295.

Mass of GRF(1-29) = 3366.88 g/mol
Mass of CJC-1295 = 3647.17 g/mol

The difference is about 280 g/mol which would mean you get about 7.5% more GRF(1-29) per unit w/o the Lys linker (DAC) then with it.

does it make sense to use cjc1295 IV?

No. IV and subcutaneous injections result in similar availability & utilization profiles for bolus amounts. Constant infusion is a different method that can't really be duplicated w/o the IV (it has no relevance to us though).

 

[Wise Guy]

Alternate day fasting.

I'm a huge fan of the primal blueprint, made popular by marksdaily apple, which advocates that as well.