Ipamorelin and GRF 1-29 for health and longevity: An Inquiry

[2Sox]

I've been doing a little reading on these two compounds and I'm interested in knowing more about them. I'm considering adding them to my TRT protocol for better health, well being and longevity. Although I go the the gym 5-6 days a week, and I'm very interested in keeping in shape, this really doesn't have much to do with body building per se (although I am somewhat aware of the benefits in this area).
Strictly for quality of life, so to speak.

So any comments and advice about dosing etc., and the benefit of your knowledge would be much appreciated.

[2Sox]

On another forum, I found a very informative post by the author, Datbtrue. This is the first part. It's rather long but I feel it's worthwhile.

By the way, the chemical name for GRF 1-29 is Semorelin. and from what I learned from this post below, the title of my thread should really be changed to "GRF 1-29 and GHRP-2 For Health and Longevity: An Inquiry"


GHRH (Growth Hormone Releasing Hormone) + GHRP (Growth Hormone Releasing Peptide) = 10 star GH Release (**********)

GHRP (Growth Hormone Releasing Peptide aka Ghrelin-mimetic) = 3 star GH Release (***)

GHRH (Growth Hormone Releasing Hormone) = 0 or 1 star GH Release (*)


GHRPs (GHRP-6, GHRP-2, Hexarelin, Ipamorelin) are like cardiac shock paddles. You administer a GHRP and a pulse of GH is created. This is predictable and reliable across all normal people.

GHRH creates no pulse. It only adds to what ever is happening naturally. If there is a pulse occurring then GHRH increases the GH release. If no pulse is occurring when GHRH is administered then it will have little effect on GH release.
I can not speak for Dr. Crisler but he indicated that Sermorelin (GHRH) by itself was not very effective at raising IGF-1 levels. However when he added GHRP-6 with it at saturation dose (I believe administered together twice a day), IGF-1 levels increase by 1/3.

This underscores the need for both a GHRH & a GHRP.

IF you are 100% sure you have CJC-1295 (and the odds are against it) then because it is a long lasting GHRH (half-life measured in days) it will always be available which means during natural GH waves & troughs. So it behaves differently and its effectiveness in terms of absolute GH release is higher then the other forms of GHRH.

CAVEAT - CJC-1295 raises base levels of GH not the pulses. It is possible that CJC-1295 never gives the somatotrophs sufficient time to reload stores of GH at the 100% level. Normally Somatostatin by stopping GH release activity gives the cells sufficient time to build up a big store of releasable GH. So CJC-1295 no matter how much GHRP you add may not be able to effect as strong a pulse as a GHRP + GHRH.

There is no reason NOT to combine a GHRP such as GHRP-6 with your GHRH, no matter whether the form of GHRH is Sermorelin, modified GRF(1-29) or CJC-1295. There is only BIG benefit.

On the flip side you can consistently and reliably effect GH pulsatile release with a GHRP alone. Without a GHRH the amplitude will not be synergistically higher. BUT it will be a strong pulse of GH release.

One more quick point. An iu of synthetic GH is 333mcg of compound. Thats all. A unit of GH doesn't give the same effect across all normal people and even within a person there is variability.

A far better measure is GH in plasma measured in many multiple intervals over a period of time. By sampling frequently you can determine the peak of GH in plasma and when it drops to baseline.

You can then measure IGF-1 levels to determine the effect that THAT dosing had on increasing circulating levels.

You can do the same thing with GHRH & GHRP.

The problem people have is they are stuck on absolute levels of GH in circulation as being of paramount importance. It isn't.

First it is free GH that is important. Anywhere from 10% to 90% may be bound at any given time with GH-Binding proteins or prolactin-binding proteins.

Second it is pulsation that is important for growth not absolute levels. Pulses send communicative signals to the cells. GH is simply the ligand that gives form to the wave. GH has no other value except to be a part of a communication signal.

The cells respond to this wave of GH by mediating events within the cell that are responsible for metabolism, protein synthesis, further ligand transcription & synthesis in the form of IGF-1 ...some of these signaling pathways in the cell carry messages to proliferate, differentiate or induce apoptosis . These intracellular pathways are common to many different tissue populations and respond to initiation from many different types of ligands binding to various receptors.

This behavior is optimized by pulsation ...continuous GH desensitizes these pathways (and sends certain signals that are common to females to mediate certain events such as creation of specific liver enzymes)...

So it is probable that I (and anyone who understands fully) could get more out of a small amount of GHRH + GHRP then someone who administers large amounts of GH. The validity of this statement is dependent on the use of other compounds...

Finally to answer your question directly:

I believe that if your CJC-1295 is modified GRF(1-29), coupled with GHRP-6, dosed as described you will achieve your goal of GH level (i.e. 4ius) and exceed both the quantity & quality of those growth optimizing events that THAT equivalent level of synthetic GH will be capable of mediating.
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Part 2 coming soon in another post.

[Black]

I ran a GHRP-2 and Mod GRF(1-29) for 8 months. The increase in appetite was crazy. 20-30 minutes post injection it was like I hadn't ate any food for days. This made it REALLY hard to stay within my macros and caloric goal. I wanted to see what was going on so I had my IGF levels tested about 12-13 hours post injection, fasted, in the morning. My IGF levels came in at 319 (71-241 range). This was on a 5x a day saturation dose of 100mcg each compound.

I haven't tried Ipamorelin, but I've heard better things about it of all the GHRPs. Aside from the increase in appetite, I will say that at the saturation dose I was running, even with all the food, I was staying VERY lean. Right before I stopped (grew tired of all the injections), I was making a switch over to GHRP-6. Not really sure why, but GHRP-6 did NOT increase my appetite at all. I still have a bunch of 6 and Mod GRF left over and have been thinking about running it again.

To note, I never experienced any prolactin issues with these compounds (and during that 8 months I ran two short cycles, one with NPP and one with Tren , both 19-nors). Without tests though, I'm not sure what kind of an impact they had on my coritsol levels.

[2Sox]

This is part Two - extremely interesting. The same author:

Some terms:

Natural GH is a blend of isoforms. Two of those forms are equally anabolic . One makes up the majority of natural GH release, weighs 22kda and is 191 amino acids long. The other weighs 20kda and has the 15 amino acids that interact with the prolactin receptor removed. The pharmaceutical companies chose to use the 22kda form for their drug. Noone makes a 20kda form.

In addition nature stacks these forms so you get 22kda:22kda; 22kda:20kda; 20kda:20kda stacks. Noone exactly knows why. There are also some naturally occurring fragments that are released.

Synthetic GH is simply the 22kda form chosen by the drug companies.

Pulsatile release of natural GH is achieved by the hypothalamus (area of the brain) releasing the hormone GHRH (growth hormone releasing hormone) into the the pituitary where it binds to cells in the pituitary and causes the release of stores of GH isoforms to be released.

Now the cells network and coordinated this release. They actually communicate and send a strong squirt of GH into the blood stream.

The hypothalamus also creates a hormone called somatostatin which also binds to cells in the pituitary and shuts off GH release. This on/off interplay creates pulses and when we have "off" time the cells are quickly remaking GH from pieces it keeps lying around so that it is ready to release the next time GHRH comes calling.

There is a third hormone called Ghrelin which comes from the gut and is a modulating hormone. It also binds to the pituitary and increases GHRH's positive effect and reduces Somatostatin's negative effect. The artificial mickers of Ghrelin are the GHRPs (growth hormone releasing peptides).

GHRH if injected only has a really positive effect on GH release if naturally occurring somatostin isn't currently active. We have no real way of knowing though...

GHRH works well in our bodies because it travels such a short distnce and is then used but if you inject it, it breaks down quickly (in minutes) and so analogs were created to resist this.

The primary analog has 4 amino acids replaced so it increases the half-life to 30 minutes. This is often called tetra-substituted (4-sub) but it is what I refer to as modified GRF(1-29). A lot of people mistakenly call it CJC-1295.

So if you inject modified GRF(1-29) you are happy because it will survive... it is a better form of GHRH BUT again if somatostatin is currently active then the GH pulse will not be strong.

GHRPs, are needed to create a pulse. GHRPs come in several forms. GHRP-6, GHRP-2 and Hexarelin. All work the same way. The GHRPs blunt somatostatin and increase natural GHRH release. So if you inject a GHRP you create a pulse of GH which rises for 30 minutes, peaks and comes down within 2 hours. That mimics a natural pulse.

So THAT is the time to take your modified GRF(1-29) (a better form of GHRH) because it will now work since somatostin isn't around.

The studies find synergy between these two peptides. Together they create a strong pulse of GH.

Growth Hormone Receptors, reside primarily on cells in the liver and they await the ligand GH. Now a strong pulse will send GH in mass so that a bunch binds at the same time to these receptors. When GH binds to a receptor it switches on a few events. One of those events is activating the Stat5b protein or intracellular pathway. This protein when activated moves to the nucleus of the cell and initiates transcription of proteins among them IGF-1.

Stat5b needs time off and it is strongly activated after it gets a break.

Synthetic GH administration, can occur intravenously. This allows for GH to mimic a pulse by immediately hitting the blood stream. binding to receptors and then even at high doses (20iu+) it is out within 2 hours.

The other two forms intramuscularly and subcutaneously result in slower release profiles. The primary reason is that the molecule is large.

So if you dose more then 4iu subcutaneously the release profile looks like an elevation more then a pulse and it starts to last for 3,4+ hours.

Pulsing synthetic GH can be achieved by choosing 2iu, 3iu or 4iu (keep in mind intramuscular has a little faster release rate) and dosing so as to get a 2 hour rise followed by a 3 hour off time. This can be done 4 times a day or 5 times if you dose in the middle of the night.

Some people prefer 2iu and squeeze in 6 doses in a 24 hour period. This is obviously an extreme way to do it but welcome to bodybuilding...

Pulsing with GHRH/GHRPs - you can dose 250mcg of a GHRP (i.e. GHRP-6, GHRP-2 or Hexarelin) with 100mcg+ of modified GRF(1-29).

100mcg of each is a minimal clinical dose but doses as high as 400mcg at a time have some effect.

Obviously these peptides create pulses and no amount will interfere so dosing can be whatever.

For instance a lady who is about 65 uses a tiny amount pre-bed (maybe 25mcg of each). She was crippled with bone pain and had to crawl up stairs. Prescription GH was of limited effect. The mod GRF(1-29)/GHRP-6 changed her life immediately. Now 6 months later she walks 2 miles a day and even breaks into a jog when pushing the grandkids stroller. Her doctor says her bone density is that of a young person. This is just an illustration... and for bodybuilding her dosing is not sufficient...

The key though is to remind yourself that GH is just a communicative tool. It communicates different things depending on how it is released... it has zero value except for its role as a communicator.

You use the GHRH/GHRP every time you want a pulse. You ALWAYS want one pre-bed. In men the biggest amount of GH release occurs at night. GH release and slow wave sleep are positively correlated. You increase/decrease one you increase/decrease the other. These peptides really increase deep restful sleep and I have been told by many that this alone is worth it.

It takes just 100mcg of each to get this deeper sleep.

You also want to dose PWO and in the morning. That is 3 times a day. You can go as many as 6 times a day (people do... they are a bit obsessive ).

Combining synthetic GH and GHRH/GHRPs - The GHRH/GHRPs are know to act quicker then synthetic GH. By act I mean engage lipolysis if you are keeping insulin quiet and active enough to burn mobilized fatty acids but also strengthening connective tissue.

I just wrote an article for Big A's whey protein product as an excuse to talk about what specific aspects, insulin, GH, IGF-1, IGF-1/BP3, androgens, blood flow, amino acid pool, thyroid hormones contribute towards protein metabolism.

GH greatly contributes to decreasing muscle protein breakdown and preventing Leucine from being oxidized. I REALLY wanted people to see how these things work together and understand that growth hormone is not anabolic by itself but with insulin (which increases muscle protein synthesis) it is anabolic. It increases amino acid transport into muscle so insulin increased muscle protein synthesis will have a substrate to work with.

So the GHRH/GHRPs work a little faster but you are limited to whatever available stores of GH you have to create a pulse. To get a higher pulse you add synthetic GH which is also now part of a natural blend.

You would administer the GHRH/GHRP...let that pulse start going and 10 minutes later administer 2iu to 4iu of synthetic GH. That will create the biggest super-natural pulse that you can achieve and the body will see it as a big "natural" pulse.

You can repeat this.

Every day is effective. The reason EOD worked better then ED was because when you dose 12iu+ you need time off... think those graphs I referred you to.


4.jpg

With 4iu of synthetic GH and tapping out your natural stores you will saturate receptors pretty well.

Insulin will increase GH receptors as well at low dose but at 8iu the benefit goes back to zero... this doesn't by any means mean you need to hold insulin below 8iu... it is just one of many many effects of insulin... and I just note it.

Then after 5 hours you can do this again and then again. That is a far better way to use 12iu a day and with your own natural release you may end up above 20iu.
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[2Sox]

I've been thinking of doing this for some time and I'm about to take the plunge: Ipamorelin and modified GRF(1-29) just for anti-aging and good sleep.

I wanted to bump this up to find out if others have run this protocol and what have been their experiences and suggestions. Any advice? Thanks.

[jasondd1]

Ive run cjc1295 no dac and ipam 4 times a day no hunger issues. I went from an average of 130 igf-1 to 335.

Switched to cjc 1295 no dac and ghrp-2 and i get crazy hungry 15 minutes after injections. ghrp-6 is suppose to make most people even hungrier and ghrp-2 although people are different. IGF-1 after 6 weeks or so of ghrp-2 was 307. i will retest in 4-5 months.

BTW when I'm referring to cjc1295 no dac it is the same as grf(1-29). I beleive cjc1295 with dac is what the author was referring to above.

[JEVIII]

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