PEGylated Mechano Growth Factor

PEGylated Mechano Growth Factor (PEG-MGF)

PEGylated Mechano Growth Factor (MGF)

Russianstar " Experiences with MGF and PEG MGF a complete guide.
This article will discuss the use of Mechano growth factor and clear up a few myths.

WHAT IS MGF?

Mechano Growth Factor (MGF) also known as IGF-1Ec is a growth factor/repair factor that is derived from exercised or damaged muscle tissue, Its called MGF as IGF-1Ec is a bit of a mouthful and harder to identify amongst the other igf variants.
What makes MGF special is its unique role in muscle growth.
MGF has the ability to cause wasted tissue to grow and improve itself by activating muscle stem cells and increasing the up regulation of protein synthesis, this unique ability can rapidly improve recovery and speed up muscle growth.
MGF can initiate muscle satellite (stem) cell activation in addition to its IGF-Ireceptor domain which then in turn increases protein synthesis turnover, and therefore can if used correctly improve muscle mass over time.
The liver produces 2 kinds of MGF splice variants of igf..
1) IGF-1Ec This is the first phase release igf splice variant and it appears to stimulate satellite cells into activation, This is the closest variant to synthetic MGF.

2) liver type IGF-IEa this is the secondary release of igf from the liver, and its far less anabolic.

MGF differs from the second variant IGF-IEa as it has a different peptide sequence which is responsible for replenishing the satellite cells in skeletal muscle, in other words it is more anabolic and longer acting than the systematic release of the second MGF liver variant.

So just think of MGF as a highly anabolic variant of igf. After you have trained, the IGF-I gene is spliced towards MGF then that causes hypertrophy and repair of local muscle damage by activating the muscle stem cells as well as other important anabolic processes, including the above mentioned protein synthesis, and increased nitrogen retention.

In rats some studies have shown muscle mass increases of 20 percent from a single mgf injection.. somehow I think many of these studies are not accurate, however the potential is undeniable.

HOW TO USE MGF

Now when you train what happens to your muscles, they break down, the cells are damaged, muscle tissue needs to be repaired and your body produces 2 forms of MGF splice variant, The first initial release of the above mentioned number 1 variant from the liver helps muscle cell recovery, if there is no MGF then muscle cells die, that's the large and small of it.
As muscle is a post-mitotic tissue and as such cell replacement is not a means of tissue repair , If the cells are not repaired they die and your muscles get smaller and weaker.
The muscle The pool of these stem cells is apparently replenished by the action of MGF, which is produced as a pulse following damage.

Now with synthetic injections of MGF you can increase the pulse and so speed up recovery, and increase the muscle tissue cells by stimulating satellite cells into full maturity. 200mcg bi laterally is the very best choice of dosing in muscles trained.
The only problem with MGF and this is the reason I don't like it, is that it has such a short half life, just a few minutes, between 5-7, and it needs to be used immediately post workout as it wont work if muscle tissue hasn't been damaged, that's why for me personally i think the best option is PEG MGF.
Nevertheless MGF has a huge role to play, and is administered to those with muscle wasting diseases and for those who are elderly and have lost muscle mass for good reason, it is EXTREMELY anabolic.


HOW TO USE PEG MGF



This is a very important section.
When using MGF that's pegylated that's the addition of Polyethylene glycol, its a non toxic additive that increased the half life of MGF from minutes to hours.
This means its uses and versatility make it a tremendous addition to a bodybuilders arsenal.
I have found it most effective as its effects are systematic, that means they have a whole body effect wherever muscle has been damaged or is diseased.

The next aspect we need to look at is how to make the most use of a long acting version of MGF.
When your muscle is damaged your body releases a pulse of an MGF splice variant as i outlined above, followed by a less anabolic longer acting version from the liver... So it seems a waste to inject MGF at this time as you will just blunt your body's own release, your not enhancing it.
So using PEG MGF on non workout days is actually the very best route, the muscle has been damaged, so there are plenty of receptors for MGF, the effects are systematic so all muscles will be helped to recover through increased nitrogen retention, protein turnover, and satellite cell activation. Recovery is just going to sky rocket.
Doing this means your increasing the length of your body's own mechanism for muscle repair and growth, your opening up the anabolic window.

NOW PLEASE TAKE CAREFUL NOTE.

Running PEG MGF in synergy with IGF is perfect but there are things you need to know.
If you dose them at the same time, as IGF has such strong receptor affinity, The effectiveness of MGF will just be wasted.
The best option and the very best choice I feel is this....
IGF DES on workout days Pre workout, or IGF1-LR3 this wont blunt your body's own MGF release from the liver, and whereas IGF1-LR3 has a more systematic effect and only a very small localized anabolic effect, DES on the other hand is very anabolic in a localized way, so bring up lagging muscle parts with DES, and then the following day Dose MGF at 200-400mcg subq to increase recovery and the mechanism for growth. Perfect synergy.

Over a 4 week run i noticed about 4lb increase with the PEG MGF and DES partnership. And roughly the same weight in fat loss, very impressive, some though have noted far greater increases in muscle mass.
If your on an AAS cycle there is no need for the addition of DES as IGF levels will already be elevated, then the addition of PEG MGF can take your recovery and gains to a new level.

STORAGE ETC

Dosing 3 times a week is best, and 1ml of BA water for every 2mg is optimal. Storage in the fridge for up to 6 months. Avoid exposure to heat or sunlight.

According to RS nice protocol of IGF DES and PEG MGF will be
IGF DES during workout 80mcg and above ( about 4X week)
PEG MGF next day of workout of day 200-400 mcg at 2 pm (about 3X week)

but for beginners
50mcg IGF DES and 200mcg PEG MGF is sufficient
My bro got nice results with these peptides
Gained about 8 pounds pure muscle mass in just 5 weeks

__________________
Current cycle
week 1-16 test e 500mg/week
week 1-14 deca 400mg/week

 

Quick summary: MGF is a splice variant of the IGF produced by a frame shift if the IGF gene. MGF increase the muscle stem cell count, so that more may fuse and become part of adult muscle cells. This is a process required for adult muscle cells to continue growing.

Why PEGylate MGF?
MGF exhibits local effects in skeletal muscle and without modification is not systemic (can’t travel through the body). The problem with synthetic MGF is that it is introduced IM and is water based so it goes into the blood stream. MGF is not stable in the blood stream for more than a matter of minutes. Biologically produced MGF is made locally and does not enter the bloodstream and is short acting so stability is not an issue. By PEGylating the MGF we can make synthetic MGF injected IM almost as efficient as local produced MGF. Clinically proven Advanced Pegylation, the technology of polyethylene glycol (PEG) conjugation, holds significant promise in maintaining effective plasma concentrations of systemically administered drugs. It does this by surrounding part of the peptide with a unique structure made of polyethylene glycol, which can be attached to a protein molecule. The result of a correct PEGylation is similar to the protective mechanism of a turtle shell. The polyethylene glycol groups protect the peptide but don’t surround it completely. The active sites of the peptide are still free to do their biological function. In this case the shell is a negative charged shield against positively charged compounds that would affect the protein. This also provides a nice steric chamber for the peptide to reside in. So it’s a happy turtle

Neurological research has shown that utilizing PEGylated MGF resulted in a longer more stable acting version of the MGF peptide in serum/blood.

Bottom line
PEGylation can improve performance and dosing convenience of peptides, proteins, antibodies, oligonucleotides and many small molecules by optimizing pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. PEGylation also can increase therapeutic efficacy by enabling increased drug concentration, improved biodistribution, and longer dwell time at the site of action. As a result, therapeutic drug concentrations can be achieved with less frequent dosing—a significant benefit to patients who are taking injected drugs.

The PEG itself does not react in the body and is very safe. PEG has been approved by the US Food and Drug Administration (FDA) as a base or vehicle for use in foods and cosmetics and in injectable, topical, rectal and nasal pharmaceutical formulations. PEG has demonstrated little toxicity, is eliminated intact by the kidneys or in the feces and lacks immunogenicity. The risk associated with current PEGylated drugs are due to the way the drug itself acts not the PEG. MGF, as it is being currently sold, is getting a bad rep from people due to the fact they feel that they are not seeing gains from it. Many people believe that the use of MGF in their cycles or protocols just flat out won't work, however, this is far from the truth.
More MGF information
Complete Overview of MGF or IGF-IEc

From its sequence, MGF is derived from the IGF-I gene by alternative splicing and has different 3' exons to the liver or systemic type (IGF-IEa). It has a 49 base pair insert in the human, and a 52 base pair insert in rodents, within the E domain of exon 5. This insert results in a reading frame shift, with a different carboxy (C) terminal sequence to that of systemic IGF-IEa. MGF and the other IGF isoforms have the same 5' exons that encode the IGF-I ligand-binding domain. Processing of pro-peptide yields a mature peptide that is involved in upregulating protein synthesis. However, there is evidence that the carboxy-terminal of the MGF peptide also acts as a separate growth factor. This stimulates division of mononucleated myoblasts or satellite (stem) cells, thereby increasing the number available for local repair

During the early stage of skeletal muscle development, myoblasts (muscle stem cells) fuse to form syncytial myotubes, which become innervated and develop into muscle fibers. Thereafter, mitotic proliferation of nuclei within the muscle fibers ceases. However, during postnatal (after development) growth, additional nuclei are provided by satellite cells (myoblast) fusing with myotubules. Muscle damage-recovery seems to have a similar cellular mechanism, in that satellite cells become activated and fuse with the damaged muscle fibers (reviewed by Goldring et al. 2002). This is also pertinent to certain diseases such as muscular dystrophy in which muscle tissue is not maintained and which have been associated with a deficiency in active satellite (stem) cells (Megeney et al. 1996; Seale & Rudnicki, 2000) and in myogenic factors (Heslop et al. 2000). Skeletal muscle mass and regenerative capacity have also been shown to decline with age (Sadeh, 1988; Carlson et al. 2001). The reduced capacity to regenerate in older muscle seems to be due to the decreased ability to activate satellite cell proliferation (Chakravarthy et al. 2000). The markedly lower expression of MGF in older rat muscles (Owino et al. 2001) and human muscle (Hameed et al. 2003) in response to mechanical overload has been associated with the failure to activate satellite cells, leading to age-related muscle loss (Owino et al. 2001). Your muscle cells can not grow once they have reached a certain size unless they obtain more nuclei from the myoblast. MGF increases the myblast available to donate their nuclei to the adult muscle cell.

“MGF appears to have a dual action in that, like the other IGF-I isoforms, it upregulates protein synthesis as well as activating satellite cells. However, the latter role of MGF is probably more important as most of the mature IGF-I will be derived from IGF-IEa during the second phase of repair. Nevertheless, it has been shown that MGF is a potent inducer of muscle hypertrophy in experiments in which the cDNA of MGF was inserted into a plasmid vector and introduced by intramuscular injection. This resulted in a 20 % increase in the weight of the injected muscle within 2 weeks, and the analyses showed that this was due to an increase in the size of the muscle fibers (Goldspink, 2001). Similar experiments by other groups have also been carried out using a viral construct containing the liver type of IGF-I, which resulted in a 25 % increase in muscle mass, but this took over 4 months to develop (Musaro et al. 2001). Hence, the dual role MGF plays in inducing satellite cell activation as well as protein synthesis suggests it is much more potent than the liver type or IGF-IEa for inducing rapid hypertrophy.”

These results are based on actual transplantation of the DNA coding for the peptides. This is a permanent effect and much more potent than IM injections of the peptide itself. You will not see a 20% increase in muscle mass through IM injections as claimed above.

PEGylated MGF dosing Protocols
The PEGylated version is going to be much longer lasting making a 1-2 dose per week procedure possible. I still think its best used with IGF or AAS to maximize the benefits so here are some sample protocols

Once a week PEG MGF/ IGF
Sunday 100-300 mcg MGF you can choose to site inject if you wish. I think splitting large doses may benefit.
Monday –Fri IGF 50mcg e/d

Twice a week PEG MGF / IGF
Sunday and Wed MGF 50-150 mcg
MT, Th, F IGF 50 mcg

These protocols are just to start as this is brand new feel free to tweak them if you like. I will update them after we have done some testing.

 

MGF is a splice variant of the IGF gene which increases stem cell count in the muscle and allows for muscle fibers to fuse and mature. This is a process required for growth of adult muscle. Natural MGF is made locally and does not travel into the bloodstream. Synthetic MGF is water based and when administered intramuscularly, travels into the bloodstream. MGF is only stable in the blood stream for only a few minutes.

PEGylation is the act of attaching a Polyethylene glycol (PEG) structure to another larger molecule (in this case, MGF). The PEG acts as a protective coating and the theory here is that this will allow the MGF to be carried through the blood stream without being broken down.

 

Background

I have to be honest here, and say that in my estimation, PEGylating MGF is basically something a research chemical company did to have a bit of a market with no competition for awhile. That’s not to say that it’s not a decent product, but honestly, in this particular case, I feel that marketing was in the drivers seat with the development of this version of MGF, and science was in the backseat asking “are we there yet?”.

 

Action

MGF is produced biologically when muscle fibers are broken down through resistance (weight training). It is a potent factor in muscle growth. MGF stimulates muscle growth, creates new muscle fibers, promotes nitrogen retention and increases protein synthesis. This compound is commonly used for overall growth of muscle and to promote growth in body parts that are not up to par with the rest of the user's physique. Results usually depend on dosage. Fat loss and strength increases are not typically seen with MGF's use (as they are in IGF-1 use).

The PEG itself is safe for use as it is approved by the US Food and Drug Administration (FDA) and does not react in the body. The PEG is not broken down in the body and excreted (intact) through urine or feces. Any risk associated PEGylated drugs is due to drug itself not the PEG per se.

 

Technical Data

In a study on older rodents, muscle fiber reduction in their older muscles was found to be attributed to decreased activity of satellite cells (1). After a certain size was reached, growth ceased. In the presence of MGF, satellite cells became activated and hypertrophy in mature muscles continued.

In experiments where MGF was administered intramuscularly, there was a 20% increase in the weight of the injected muscle fibers within 2 weeks (2). In further studies, it took 4 months for IGF to cause a 25% increase in muscle mass (3). MGF was found to be more potent than IGF-1Ea in rapid muscle growth (4).

[Note: This data is on “regular” MGF, not the Pegylated version….we can assume similar results, however]

 

User Notes

Although the science looks impressive on paper, in the real world, we see something totally different. While PEGMGF should have theoretically given the athletes who use it better results than regular MGF, it struggles to provide even the same results at a higher dosage (judging from the athletes I have personally spoken to).

So does that mean it’s useless?

No, not at all. Not entirely…

 

I think that the PEGylation is actually a potentially useful addition to MGF if properly used. If we assume that the PEGylation will extend the life of the MGF in the body somewhat, then we can use it in a very specific manner to help our gains. It is nowhere near as good as regular MGF though, and I wouldn’t use it unless I really had the disposable cash on hand.

 

I feel that, based on conversations with several athletes and bodybuilders, that PEGMGF is best used in conjunction with (not instead of) regular MGF (and IGF). I feel that if one were to use my Peptides protocol (to read about that in detail, check out the article “Peptides: The Next Frontier in Hypertrophy”), I think that PEGMGF is probably best used on off-days from training, to keep MGF levels elevated and get additional hypertrophy from the longer releasing PEGMGF.

 

So, along with regular MGF and Lr3IGF-1, if I felt it to be necessary, I might throw in some PEGMGF on off-days from training, to get additional growth (and again, if it were me, I’d probably recommend 400-500mcg of PEGMGF on off days, with a regular dose of 200mcg of regular MGF + 100mgs of Lr3IGF-1 on training days, as per my article).

 

For most athletes I’ve spoken to and worked with, this is what we’ve found to be optimal. Again, though…I’m not very fond of this product, and it’s best used (if at all), as a possible adjunct to an IGF + MGF cycle, and never in place of regular MGF. Unfortunately, it just didn’t pan out as people hoped it would, but it’s not a complete waste of money.

More Peptide Info...

Hexarelin

Hexarelin is a synthetic hexaptide which has GH-releasing properties. Hexarelin, administered subcutaneously produces a dose-dependent GH response from the Pituitary.

The advantages of having HGH secreted in larger amounts in the body would be similar to what happens when injectable growth hormone is administered. Effects from GH include increased bone mineral density, increased mitosis and meiosis which leads to more muscle mass, triglyceride hydrolysis which causes prominent fat loss, connective tissue strengthening, and improved skin elasticity.

GH secretion also leads to the liver secreting more IGF-1 (Insulin-Like Growth Factor One), which by itself has a host of effects similar to GH. Users of IGF-1 typically experience increased strength and muscle mass, as well as a very pronounced fat loss.

Therefore, by injecting Hexarelin, the user will experience all of the effects of both Growth Hormone as well as IGF-1. However, since Hexarelin actually stimulates the body to produce more GH, it may be likely that the eventual shutdown of the body’s natural GH production may be avoided, as is seen with injectable GH. For this reason, many athletes use Hexarelin alone, but others have used it after a Growth Hormone or Insulin-Like Growth Factor one cycle, to “jumpstart” their own natural GH and IGF-1 production.

More Peptide Info...

Tissue Growth & Protection and Practical use of peptides

Tissue Growth & Protection and Practical use of peptides

Peptides, Tissue Growth & Protection and Practical use surrounding them Hello all of you in internet land!
Today I wish to cover the subject of peptides and their possible uses.
There seems to be a lot of people out there unsure of what peptides are or flat out think they are some sort of gimmick.
I was at one point in time in the same boat, so no worries keep reading and you might learn something. After many years of research on this topic and countless personal experiences with peptides I feel I am qualified to try to help others out there by putting together this article covering the most popular peptides, their uses, how to use them safely and most effectively.

What so WHAT in the world is a PEPTIDE???

Isn’t that the stuff in my wife’s shampoo???

Well…… I might be. But not all peptides are the same! Just like not all amino acids are the same.
Peptides are actually very similar to amino acids (protein molecules) believe it or not.
A peptide is a short, large molecule of an amino acid molecule that can bind chemically to other molecules to form a larger molecule by peptide bonds. They are listed as a peptide or protein depending on their size.

I know it sounds confusing and in some ways it is. But it is not too hard to understand them.
There are many kinds of peptides out there some are your basic protein type peptide that I will not bother to cover at this time or that would make this more of a diet article than a peptide article. Another is a “peptide hormone” they are secreted into the blood stream and have an endocrine function in the body.[1]

There is even something called a neuropeptide. One of many for e.g. is DSIP (Delta Sleep-inducing Peptide). They are small protein-like molecules used by the neurons to communicate.
They are much smaller than a neurotransmitter and are considered neuronal signaling molecules and they affect many functions in the brain like; pain, hunger, memory and can even effect you’re learning abilities!
Still think Peptides might be a gimmick? HA I sure don’t. I think they are GREAT!
No I won’t be talking about neuropeptides today, but I wanted to at least mention them because I feel they are pretty cool and very important.


Today I will be talking about Peptide Hormones!

Peptide hormones are not the same as steroid hormones.
Steroid hormones are synthesized from cholesterol, and are lipids (they are fat based). While peptide hormones are proteins and are formed by a sequence of amino acids.
As mentioned above these are the ones that have physical effects on the body like growth and repair and has been of very big interest to the bodybuilding scene and in recent years I feel at a massive scale due to the internet and many places selling these peptides.
I felt I really should put something together about these powerful peptides and how they might help you in your quest to recovery, fat loss and growth.



I will start with the basics of what each one does then I will get into more detail on how you can use them safely and effectively.

GHRP-2
Is a human growth hormone secretagogue. That means it stimulates the body's own release of HGH. It is a ghrelin receptor agonist is also seems to have some protective effect on some tissues and an anti-inflammatory effect as well. The excessive hunger some feel with GHRP-6 use does not seem to be an issue with GHRP-2. The half-life is about 20 minutes so multiple doses per day are optimal.

GHRP-6
Is also a human growth hormone secretagogue and stimulates the body's own release of HGH. It is a ghrelin receptor agonist and also seems to have some protective effect on some tissues and an anti-inflammatory effect as well. The half-life is about 20 minutes so multiple doses per day are optimal.
*Note: GHRP-6 seems to cause excessive hunger in some people compared to GHRP-2. It is not a bad thing per say but depending on if your bulking or cutting you may prefer one over the other.

CJC-1295
Is a growth hormone releasing hormone (GHRH) and it aides in the stimulation of the pituitary gland to increase production of growth hormone and stimulates GH and IGF-1 secretion. It will keep a steady increase of HGH without an increase in prolactin as can be an issue for some peptides of this nature. It is an analog to a peptide that is naturally produced to stimulate pituitary production of growth hormone. It has a half-life of about 7-10 days. This means once a week dosing is optimal in most cases.

CJC-1293 (CJC w/o Dac)
Is also a growth hormone releasing hormone (GHRH) and it aides in the stimulation of the pituitary gland to increase production of growth hormone and stimulates GH secretion. It is an analog to a peptide that is naturally produced to stimulate pituitary production of growth hormone. The GH pulse from a single administration of CJC-1293 seems to be greater than that of CJC-1295 but duration is shorter. There is debate on which is better but both are useful regardless.

IGF1 Des
IGF-1 Des is an IGF-1 analogue of our native igf1 with the last 3 amino acids in the IGF-1 chain removed. That leads it to have little protein binding (good thing), but similar action causing it to be about 10 times more potent than normal IGF-1.[2] The active life is still fairly short, only about 20 minutes making multiple doses daily optimal for some users while others still feel once a day dosing is still worthwhile and the way to go.

IGF1LR3
Is also an IGF1 analogue with a 13 amino acid extension at the N-terminus. The alteration leads to less binding in the body greatly extends its half-life from 20min to about 20+ hours. Once a day dosing is optimal.

IGF1Ec / Mechano Growth Factor (MGF)
IGF1 Ec is derived from IGF-I but its effects differ from the systemic IGF-I produced by the liver. It is released as a pulse following muscle damage, is involved in the activation of muscle stem cells and also seems to protect the myocardium against ischaemia, which improved cardiac function after heart attacks. There is debate on dosing but i feel post workout (once daily even on non workout days) is a good way to go about it.[3]

MT2
Melanotan II (MT2) is a melanocortin. Melanocortins (MCs) are a family of multifunctional peptidergic hormones. MT2 is an analog of these and plays a role in the tanning process but will vary between skin types with its use. It is not really used in any growth as HGH or igf1 would be, but I feel due to its potential skin protection that I should add it in this article even if tanning is not the main focus of this article.



As you can see all this stuff seems to revolve around IGF1 and HGH, so to understands its effects does not mean needing to fully understand each and every peptide (though a basic knowledge should be known about each one you use). Each peptide is working as either an IGF1 analog or as a HGH releaser and HGH converts to IGH1 giving most of its tissue growing effects anyway.

It’s more understanding what IGF and HGH do in the body, to fully understand what these peptides can potentially do for you.

I would like to talk mainly about IGF1 as I feel it is the main cause for growth over that of HGH solely.[4]
The liver is the organ mostly responsible for the production of serum IGF-I even when taking exogenous HGH it is still mainly converted in the liver.

IGF-1 acts differently in different types of tissues its not all tissues grow from its effects. When active in muscle cells and associated cell’s they stimulate growth by increasing protein synthesis along with amino acid absorption. IGF-1 also plays a role as a source of energy; IGF mobilizes fat for use as energy in adipose tissue by preventing insulin from transporting glucose across cell membranes. This results in the cells having to switch to burning off fat as a source of energy which I feel is a great quality about IGF-1.IGF also seems to mimic's insulin in the human body. It makes muscles more sensitive to insulin's effects.[5][6]

I think one of the most interesting effect’s IGF has on the body is its ability to cause hyperplasia, that is when an actual splitting of cells occurs leading to more cells. You are basically your growing more cells with the use of HGH and IGF-1.
Hypertrophy is what occurs when practising weight training and steroid use. Hypertrophy is simply an increase in the size of muscle cells but not growing new cells. In humans after you are done puberty you mostly have a set number of muscle cells that you have developed with that doesn’t vary much.All you would be able to do is increase the size of these muscle cells, but you don't actually gain more of them.
This is not good for someone with “bad genetics” in the area of muscle cells.
With IGF use you are able to cause hyperplasia which increases the number of muscle cells and gives you the ability to change your genetic capabilities in terms of muscle tissue and cell count.[6]
Being able to alter a person’s capacity to build muscle density and size is an awesome thing to have control over.
When you do a “cycle” of HGH releasing peptides or even straight use of IGF1 analogs on its own, you not only add to growth and recovery while on them, you give yourself a greater number of cells to work with and down the line grow then.

When you finish a cycle of IGF-1…. in a way you are not really finished because you are still left with these new cells regardless of stopping the use of IGF1 or HGH releaser peptides and that is one of the things I just LOVE about HGH and IGF1. The fact you have residual effects is awesome for muscle building!


OK, OK we know igf1 causes growth of size and cells, but how do I use this stuff effectively?
Well by knowing the basics of each peptide, how they might have a synergy when used together and fully understanding the effects of HGH and igf1 that’s how!

Unfortunately a lot of the use of IGF1 and HGH by bodybuilders and athletes is an underground trend of their use and you might not find some of the info needed to stack them optimally together or use them in a home setting.
I wish to give you some of that information here.

Secretagogues are different from GHRH's, they share no sequence relation and derive their function through action at a different receptor and it has been established that the use of Growth Hormone Releasing Hormone (CJC1295 is one for e.g.) and a Growth Hormone Releasing Peptide (GHRP-6 or GHRP-2 for e.g.) together results in synergistic release of GH from pituitary.
It is like saying 2+2=5 not 4, if you get what I am trying to say.

I strongly rec stacking a GHRP with a GHRH for optimal results in tissue growth and fat loss, even if also using an IGF1 analog in the same cycle as some like to do.


Here are some good examples of “peptide cycles” (Taken Sub Q):

1#
Wk1-8 40mcg ed IGF-1LR3

2#
Wk1-12 1000mcg (1mg) every week CJC-1295
Wk1-12 100mcg 2-3X ed GHRP-2 or GHRP-6
Wk1-12 10-20mcg ed IGF1 Ec (post workout’s)

3#
Wk1-12 100mcg 2-3X ed CJC-1293 (CJC w/o Dac)
Wk1-12 100mcg 2-3X ed GHRP-2 or GHRP-6

4#
Wk1-8 40mcg ed IGF-1LR3
Wk1-12 100mcg 2-3X ed CJC-1293 (CJC w/o Dac)
Wk1-12 100mcg 2-3X ed GHRP-2 or GHRP-6

5#
Wk1-8 10-20mcg 1-2X ed IGF-1 Des

6#
Wk1-8 10-20mcg 1-2X ed IGF-1 Des
Wk1-12 100mcg 2-3X ed CJC-1293 (CJC w/o Dac)
Wk1-12 100mcg 2-3X ed GHRP-2 or GHRP-6

7#
Wk1-8 10-20mcg 1-2X ed IGF-1 Des
Wk1-12 1000mcg (1mg) every week CJC-1295 (Sub Q)
Wk1-12 100mcg 2-3X ed GHRP-2 or GHRP-6

8# (MT2 cycle is for tanning purposes only, dependent on skin type and these are guidelines only)
Wk1-4 0.5mg 2-3X a week of MT2 (10min tan every week)
Wk4-8 0.5mg 1X a week of MT2 (10min tan every other week)
Wk8-? 0.5mg 1X a month of MT2 (tan and dose as needed) *maintenance

These cycles above would be optimal ways of using these peptides for muscle growth and fat loss.

Using one or more of the HGH releasing peptides along with an IGF peptide like IGF-1lr3 could lead to growth and more fat loss over just the use of IGF-1lr3.
But the use of one or more of the HGH releasing peptides without IGF-1 could lead to less total gains in mass as well. So stacking is goal dependent.
I feel they stack together very nicely personally and I highly recommend IGF1LR3 to my friends new to and interested in peptides.

IGF1lr3 or IGF1 Des are good peptides to start out with due to the simple ease of their.
Then once you feel comfortable I would highly recommend stacking it with one of the GHRP’s and GHRH’s for maximum results.

There are new discoveries every day in the field of “the human body” and I would be VERY Happy If I had some effect on this knowledge spreading, so I hope you learned something and enjoyed my article on these peptides and how to use them most effectively and safely.

I look forward to helping all I can and making more of these kinds of informative articles.
Till the next time,

More Peptide Info...

PEG-MGF FAQs

PEG-MGF FAQs

Does PEG-MGF have to be injected into the muscle?
Due to its long half-life, PEG-MGF (Pegylated Mechano Growth Factor, also known as IGF-1ec) does not need to be injected into muscle tissue but given that MGF is normally released in the body as a result of muscle trauma, it is recommended, but not essential, that you inject PEG-MGF after weight training into the muscle group just worked. Since injections are done with an insulin syringe this limits most people to bicep, calf muscle and possibly shoulder injections. Other muscles generally have a layer of subcutaneous fat covering them which will prevent an insulin syringe from reaching the muscle. The only alternative would be to use a syringe barrel + longer syringe (such as 25g) to inject, however dosing would be difficult with this method.
Thankfully, since the addition of PEG (pegylation) to MGF takes its half-life from a few minutes to a few days, an injection into a muscle group which was not just trained, or a sub-q injection, means the peptide will still eventually reach the desired receptors and carry out its positive effects on muscle recovery and growth.

When should I inject IGF-1 LR3 and PEG-MGF and how much?
Due to its long half-life and mechanism of action the injection timing of IGF-1 LR3 is not so critical, however most people inject it pre or post weight training when the muscle receptors are more sensitive. The usual IGF-1 LR3 dosage is 50mcg per day taken on weight training days only. Since PEG-MGF is a growth factor which is naturally only released in response to muscle trauma (such as weight lifting), you should always aim to inject as soon as possible after your workout at a dosage of at least 200mcg per injection.

How long should I inject IGF-1 LR3 and PEG-MGF for?
Both IGF-1 LR3 and PEG-MGF should be used for 4 weeks at a time with the same amount of time off, i.e. one month on, one month off. The reason for this is because the products become less effective at this point due to down-regulation of the receptors (i.e. your muscles are no longer sensitive to the peptides). You therefore may like to take IGF-1 LR3 for one month, then MGF for a month and keep rotating them so you will be using either one of them continuously for maximum results.

Can IGF-1 LR3 and PEG-MGF be taken together?
It is not recommended to inject IGF-1 LR3 and MGF together since they compete for the same receptor sites and IGF-1 LR3 would be a much more powerful binder and probably render the PEG-MGF useless. A better solution would be to rotate them and take IGF-1 LR3 for 4 weeks then PEG-MGF for 4 weeks and keep repeating. If you did want to take both products together the best routine would be to inject IGF-1 LR3 first thing in the morning before breakfast, lift weights in the afternoon and take your PEG-MGF post workout directly into a muscle. It's best to avoid IGF-1 LR3 injections in the evening since it can hinder the body's natural release of growth hormone due to negative feedback on the hypothalamus.

My IGF-1 levels are normal on blood tests; shouldn't they be higher when using IGF-1 LR3?
IGF-1 blood tests look only for bound IGF-1 while the purpose of IGF-1 LR3 is to keep it unbound and therefore bioavailable meaning it will not show up on conventional blood tests. It is the same scenario as for blood tests which examine testosterone levels. Many people can have results showing low or normal testosterone levels, but have high "free testosterone" levels - which is much more important, since only testosterone which is not bound to SHBG (sex hormone binding globulin) can be used by the body.
Therefore your levels of IGF-1 on a blood test are not of much importance and do not take into account the increase from IGF-1 LR3 usage, as they only look at bound IGF-1 (which cannot be used by the body since it's attached to binding proteins).

What are the side effects of IGF-1 LR3 and PEG-MGF?
With PEG-MGF no side effects have been noted by users of the peptide. With IGF-1 LR3 however minor side effects have been mentioned such as hypoglycaemia (low blood sugar), which occurs due to the product being "insulin-like". This can be overcome by consuming carbohydrates post injection to stabilize blood sugar. Some users also notice very strong "pump" effects in the muscle which can make it difficult to do high repetition sets of weights.

How long is IGF-1 LR3 stable after mixing?
If your IGF-1 LR3 peptide vial is freeze-dried, then it will usually be stable for at least 2 months (8 weeks) in the refrigerator after being reconstituted (mixed) with a sterile solution. Since the recommended daily dosage is 50mcg, even if the product is only injected 3-4 times per week this should be plenty of time to use the vial before it could possibly degrade.

What solutions can IGF-1 LR3 be mixed with?
Legitimate manufacturers of IGF-1 LR3 peptides have advised that there is no advantage to specific types of mixing solution over others. The peptide is equally soluble and stable in acetic acide 0.6% solution and bacteriostatic water.

Should IGF-1 LR3 be injected into the muscle or fat?
Due to its long half-life, even if you injected your IGF-1 LR3 peptide into fat, it would still find its way to the binding sites in the muscles of your body. If you have no issue with either type of injection, an intramuscular injection is recommended to allow the start exhibiting its localized effects immediately.

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Tips for Melanotan 2 Success

Tips for Melanotan 2 Success

Things you should know:

Dose escalation. With Melanotan 2, a good starting point is .25 mg. The goal is to find the smallest effective dose possible while limiting side-effects. Everyone is different, not all suppliers are created equal.

Anti-histamines. Anti-histamine use can help reduce post injection nausea from MT-2. The anti-histamine reduces the probability of the body reacting that way to the introduction of the foreign compound. Claritin (Loratadine), Zyrtec (Cetirizine), Benadryl (Diphenhydramine) are appropriate.

Cover your eyes and face. Fair skinned MT-2 users particularly. As limited UV exposure is essential for a natural looking tan, experiment with your body first. Try and avoid exposing your face until your 2nd or 3rd Melanotan cycle. Many out there overexpose themselves leaving their faces looking extra dark. Purple lips, wrinkles and freckles are just some of the lovely characteristics misuse can bring. Your face is sensitive, protect it. Achieving a balanced tan is what most of us are after.

Ignore dosing charts. Rely on a common sense approach of dose escalation and experimentation. Charts which float around the net often have not kept up with the collective and advocate dangerously high dosages.

Read current guides. Find the best information from many sources. Misinformation, trends, fades, and propaganda run rampant in the marketplace. Successful how to guides often share many similar principles which are extremely helpful to pay attention to.

Rely on referrals. A seller who has stood the test of time and has referrals is likely looking out for you. A seller or area touting concerns about fillers, standards or origins often are misguided.

Log & support user logs. Creating or simply participating in user logs offers insight into the thought process of the MT-2 user. The market relies on the collective knowledge. Rare there are detailed instructions applicable to you and your specific objectives. Ask questions. You will be surprised how many tricks of the trade rise to the surface.

Weight-loss. Clinical data is on the rise. For now, many users believe MT-2 has fat loss/appetite suppression possibilities. Maximize fat loss when you use MT-2 on days or during time periods when you are fasting or in a caloric deficit.

Travel sized Peptides. Although reconstituted MT-2 lasts for months when refrigerated, peptides are perishable items and require a certain level of care. 10mg MT-2 has been the industry standard size. With the dosage charts on the decrease, dose escalation on the increase, 5mg MT-2 offers further efficacy. Rather take a 10mg or 5mg MT-2 on a 4 day vacation? What about a 2mg PT-141 for the weekend? These are some options to take note of. From experience I can tell you there is not much exciting about bringing a 10mg vial on a trip only to pitch 5-8mg of the product in the trash before the flight home.

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Ipamorelin profile

Ipamorelin profile

 Firstly just so everyone knows what we are talking about here is a look at one of the best peptides available.

Ipamorelin is a GHRP (growth hormone releasing peptide) receptor-active GH secretagogue, it doesn't significantly effect cortisol or prolactin, so this makes it highly specific for GH release.

Aib-His-D-2-Nal-DPhe-Lys-NH2

It has also been found that 12 weeks of treatment with ipamorelin increased bone mass in young adult female rats in one study that can be found on pubmed.

It is important to remember that Ipamorelin is a ghrelin mimetic, and an analog to ghrelin.
However it doesn't cause the kind of hunger feelings caused by ghrp-6.
Ipamorelin acts with synergy when used during your own GHRH (growth-hormone releasing hormone) pulse or when coadministered with GHRH or a GHRH analog such as Sermorelin or cjc.
The synergy comes about due to both the obvious suppression of Somatostatin and the increases in GH release per-somatotrope, while GHRH increases the number of somatotropes that release GH.
Due to the fact that its selective and doesn't really alter cortisol or prolactin levels, this makes Ipamorelin a very exciting peptide, it is as effective as ghrp-6 without the increase in hunger or cortisol or prolactin serum levels, and it has another property unique to Ipamorelin.
A mega-dose of Ipamorelin results in a mega-release of GH (up to the entire amount that is actually present in the pituitary), whereas GHRP-2 and GHRP-6 have limits of approximately 1mcg/kg in humans for their maximal GH release.
I find this very exciting when used directly after training to increase recovery and in the maturation of satellite muscle cells.


Results and experiences.

I used 100mcg 3 times a day, i used it exactly as GHRP-6 in my experiences thread... I used it injected directly in to joints and areas that i have damaged and found over just a 2 week period a massive amount of improvement, in particular in my elbow where i was suffering from a strained ligament.. the pain subsided totally and full strength returned within 4 weeks.. this was after it hurting on and off for over 3 months. The pain has never returned,

As for its anabolic properties I used 300mcg straight after training to get a much larger pulse in GH, and found recovery improved vastly... over 12 weeks on this protocol I lost about 2 lbs. in bodyfat.. but as my BF is very low I think had I been bigger this number would have been considerably higher.
I saw an increase in vascularity.. improved skin texture.. very deep sleep, in fact I was feeling sleepy quite a bit through the day.. minimal water retention and about 3lb gain in mass... sadly I am at my genetic max I feel for size and find it nearly impossible to hold on to anything over my current weight, however 2lb has lasted over 3 months, with the obvious fluctuations in glycogen retention etc... I use an average weight based on 14 readings through the week to get a correct measurement.

If I combined this with something like CJC, which I hope to do very shortly i feel this could be an incredible combination.. and currently the best peptide combination.. although i still love the effects of ghrp-6, i love the hunger stimulation.
The selective effects of Ipamorelin make this a very special peptide..

Russians peptide rating..

10/10

This is a must buy and perfect to get to grips with peptides if you are a first time user.

Kind regards RS

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Peptide Combinations Guide

Peptide Combinations Guide

 

Growth Hormone (GH) and IGF-1 are naturally occurring hormones in the human body responsible for many enviable aesthetic traits such as muscle mass, leanness and a firm/even skin tone. As people age, levels of growth hormone rapidly decline and this is one of the main reasons humans put on weight, lose muscle mass and develop sagging/uneven skin. It's no surprise then that synthetic Human Growth Hormone is a sought after product for anti-aging by persons looking to remain youthful, bodybuilders looking to put on muscle mass and people in general who are looking to "tone up" or lose stubborn belly fat.


It is important to note that the products mentioned on this website are not the actual synthetic HGH (although HGH Frag 176-191 is the part of the "real" HGH which contributes to fat loss only). But in many respects these peptide analogues are far superior to the HGH 191aa drug for 3 reasons:
Actual HGH is very difficult or impossible to obtain in most countries and is one of the most faked/counterfeit drugs sold online.


If HGH can be obtained legally from a physician for anti-aging it's extremely expensive, with 10iu (units) costing as much as $200USD. As a comparison, the 10iu equivalent of GH releasing peptides (approximately half of one vial) sells online for approximately $20USD, a full 90% cheaper than actual HGH for the same, if not better, positive effects on the body.


Since actual HGH shuts down the body's natural pituitary gland, when you stop injecting it, your body's own ability to produce Growth Hormone is hindered and you will suffer a rebound of negative side effects such as fat gain, muscle loss and loss of skin tone/elasticity. This means you may end up doing yourself more harm than good. Since GH releasing peptides only stimulate your body's own natural production, there is no rebound negative effects if you stop usage.


The following guide indicates the best way to combine different peptides depending on your experience level of diet/training and also your goal:


Fat Loss
Muscle Building
Anti-Aging


As a general introduction, you should understand the different classes of peptides as this largely determines their combinations:


Growth Hormone Releasing Hormones (GHRH): include Modified GRF 1-29 and CJC-1295 DAC, are peptides which stimulate the pituitary gland to release stores of the body's natural Growth Hormone (GH).


Growth Hormone Releasing Peptides (GHRP): include Ipamorelin, GHRP-2 and GHRP-6, peptides which stimulate the release of a hormone called "Ghrelin" in the stomach, which then in turn causes GH to be released. GHRP's cause a much more significant release of GH than do GHRH, meaning that mg for mg, a peptide like GHRP-6 is three times more potent than Modified GRF 1-29. However, when taken together, they become approximately ten times more potent than either one alone.


IGF-1 Peptides: include IGF-1 LR3 and IGF-1e (also known as MGF or Mechano Growth Factor). IGF-1 is responsible for many of the positive effects of GH on fat loss and muscle building therefore they offer a good addition, especially if your goal is to build muscle, as they are both responsible for creating new muscle cells which can hypertrophy (get bigger) through weight training.


HGH Fragment 176-191: is a peptide which does not stimulate the release of GH but is instead a piece (or "fragment") of the full synthetic 191aa HGH molecule. More importantly, it is the fragment of GH which is responsible for fat loss, meaning it gives all of the fat loss benefits without any side effects.


As a general rule, regardless of your goal, if you are just looking to take one product, with the least amount of fuss and injections as possible, then it should be CJC-1295 DAC at 2mg (1 vial) per week. Due to its long half-life it causes your overall level of GH (Growth Hormone) to rise, and you will therefore see some improvements in things which go along with having higher levels of GH and IGF-1 such as improved body shape, sleep, skin and general wellbeing (although it can make you tired for the first 1-2 weeks while the body adjusts). Your dosage can be taken as just one injection per week (note that you may notice a head rush/flushing for 15-20 minutes after your injection due to the release of GABA in the body, a sign the product is working).
For information about more intricate and advanced usage of GH peptides please read on.


Fat Loss


The most potent weight loss peptide is HGH Fragment 176-191 which is the part of the Growth Hormone molecule responsible for fat burning. In HGH Frag Studies, it has been proven to reduce body fat, particularly in the abdominal area. The second most potent fat loss peptide is CJC-1295 DAC since it causes the overall GH level to rise in the body (the opposite of what happens naturally as a person gets older, which is why people tend to put on weight as they age). If your only goal is fat loss, it's often best to avoid the use of GHRP products (GHRP-6, GHRP-2 or Ipamorelin) since they can stimulate hunger and/or raise cortisol, both of which can be counterproductive to fat burning.


Diet Considerations


For GH to exhibit its fat burning effects, insulin must NOT be present. Insulin release in the body is caused mainly by consuming carbohydrates, although all types of macronutrients (carbs, fat and protein) still cause the release of insulin to some extent. Since HGH Frag works by causing the body to break down and release stored fat for use as energy, if you have recently consumed calories (food or beverage) your body will just use that for energy instead and little extra fat will be burnt. If however there is no food present for the body to use as energy, it will use the stored fat which the HGH Frag has caused to be released and you will notice reductions in body fat over the ensuing weeks.


Due to CJC-1295 DAC's long half-life the timing of meals is not important and this is what makes it an appealing addition to HGH Frag 176-191 to accelerate fat loss. To get the most out of your peptide usage for fat loss, the following guidelines should be followed:


Avoid eating/drinking anything with calories for three (3) hours either side of your injection.
Try to make all your meals throughout the day high protein, low fat and low carbohydrates (eg. meat/fish with vegetables/salad).
Have as few meals as possible during the day as periods of fasting have been shown in many studies to improve fat loss and also longevity (i.e. eating less will make you live longer).


Sample Peptide Cycles


Beginners


HGH Frag 176-191 at 250-500mcg per day.


Advanced


HGH Frag 176-191 at 250-500mcg per day + CJC-1295 DAC at 300mcg per day or;
HGH Frag 176-191 at 250-500mcg per day + Modified GRF 1-29 at 100-300mcg per day (split into dosages of 100mcg)


Example Injection Routines


Example 1 - Night Time Injection (recommended)
Ensure you do not eat or drink anything containing calories within three (3) hours of going to bed (with the exception of water, diet sodas, coffee/tea with artificial sweeteners).
Take your HGH Frag 176-191 injection just before getting into bed and your body will therefore be burning stored fat for the duration of your sleep.
If possible, do some cardio first thing in the morning and wait as long as possible before having breakfast to allow the fat burning to continue throughout the morning/day.


Example 2 - Morning Injection
Wake up and inject your HGH Frag 176-191 (250mcg to 500mcg is a good dosage depending on your budget).
Wait as long as possible before having your first meal (the longer you wait the more fat you will burn).
When you do eat, try to make the meal high protein, low fat and low carbohydrate (example meat and salad/vegetables).
If possible, try to do some cardio in the hours after your injection to increase the fat burning effect.


Note: If you are a person concerned about loss of muscle mass, you can consume a small amount of protein every 2-3 hours (amino acid tablets such as EAA and BCAA are good for this purpose and can be purchased from any health food shop or ordered online). However there is little reason to be concerned about muscle loss because when fat is available for energy, such as following HGH Frag 176-191 injections, protein and therefore muscle mass are spared.


Adding CJC-1295 DAC
You can add CJC-1295 DAC at 2mg once per week (or 300mcg each day along with your HGH Frag 176-191 injections - they can be mixed in the same syringe without any issues). You should take a break from CJC-1295 DAC every few months to give your pituitary gland a rest at which time you can continue to use HGH Frag 176-191 on its own, or you can substitute the CJC-1295 DAC with the short acting Modified GRF 1-29 at 100-300mcg per day (split into injections of 100mcg).


Muscle Building


Growth Hormone (GH) exhibits its muscle building effects mainly after its conversion to IGF-1 (Insulin-Like-Growth Factor). This makes IGF-1 an ideal choice of peptides for muscle building, especially since the IGF-1 LR3 version has an extended half-life which allows it to remain active in the muscles for many hours to complete its muscle building stimulatory effects. Likewise, if injected after a workout, the IGF-1 variant Mechano Growth Factor (also known as MGF or IGF-1e) is known to multiply muscle cells and contribute to muscle development. Furthermore, since IGF-1 is a by-product of GH, any peptide which increases levels of GH in the body such as a GHRP product or CJC-1295 product will obviously lead to increased lean muscle mass.


Diet Considerations
For Growth Hormone (GH) to perform its anabolic (muscle building) affects it requires the presence of the body's most anabolic hormone: insulin. This is in contrast to GH related fat loss which requires insulin to be absent. However, since GHRP and fast-acting GHRH (Growth Hormone Releasing Hormone) products (i.e. Modified GRF 1-29) still need time to stimulate the body to release GH from the pituitary gland, the insulin spike must come after the injection and not before, otherwise the GH release will be blunted.


The only exception to this is of course CJC-1295 DAC since it's long-half life and continual release of GH means it is not affected by food timing.
To get the most out of your peptide usage for muscle building, the following guidelines should be followed:


If injecting just a GHRP or GHRH product on their own, avoid eating/drinking anything high in fat for 3 hours before your injection and anything high in carbohydrates for 2 hours before (i.e. always do your injection on an empty stomach), otherwise the amount of GH release they cause may be significantly blunted leading to poor results.
If injecting both a GHRP and GHRH together (e.g. 100mcg of both GHRP-6 and Modified GRF 1-29) studies have proven that their ability to release GH returns to full-strength as little as 1 hour (60 minutes) post-meal. This gives users greater flexibility with their meal timings, especially since consuming sufficient calories is so critical to building muscle.
Whether injecting GH peptides alone or along with others, always wait at least 20 minutes after your injection before consuming anything. Once at least 20 minutes has passed, consume a food/beverage high in protein and/or carbohydrates to stimulate an insulin spike (if you inject in the morning and around your workout, this meal/shake should be high protein and high carbohydrates, if you inject at night this consumption should be protein only as protein is sufficient enough to spike insulin, but without the negative impact on fat gain which carbohydrates can contribute to).


Sample Peptide Cycles


Beginners


CJC-1295 DAC at 2mg per week or;
GHRP Product (GHRP-6, GHRP-2 or Ipamorelin) at 200mcg once per day.


Intermediate


GHRP Product at 200mcg + Mod. GRF 1-29 at 100mcg (2 times per day) or;
GHRP Product at 200mcg + CJC-1295 DAC at 100mcg per day (2 times per day).


Advanced


GHRP Product at 200mcg + CJC-1295 DAC at 100mcg (2 times per day) + IGF-1 at 50mcg after workouts or;
GHRP Product at 200mcg + Mod. GRF 1-29 at 100mcg (2 times per day) + PEG-MGF at 200mcg after workouts.


Example Injection Routines


Beginners


CJC-1295 DAC
2mg taken once per week, at any time of day.


GHRP + GHRH (once per day)
Inject your dosage (ensuring you have not consumed any food/beverages for at least 1 hour before, an optimal time would be first thing in the morning).
Ingest a protein only or protein and carbohydrate meal afterward to create an insulin spike.
Do weight training in the hours afterwards.


Intermediate


GHRP + GHRH (twice per day)
Inject your GHRP + GHRH peptides together in the same syringe (ensuring you have not consumed any food/beverages for at least 1 hour before, an optimal time would be first thing in the morning).
Ingest a protein only or protein and carbohydrate meal afterward to create an insulin spike.
Do weight training in the hours afterwards.
at least 1 hour after your dinner (or last meal of the day), take your second GHRP + GHRH injection.
If you are trying to control your body fat then have a protein only meal 20-30 minutes afterwards, otherwise a protein/carbohydrate meal will create a better insulin spike.


Advanced


GHRP + GHRH + IGF-1
Follow the same routine as shown above for "intermediate" persons. However, as soon as possible after your weight training you should also inject 200mcg of PEG-MGF (IGF-1e) and/or 50mcg of IGF-1 LR3 preferably into a muscle (although due to the long half-life of both products, sub-q injections are also acceptable). If injecting intramuscularly, you should make sure that the muscle you are injecting into is not covered by a thick layer of fat. Usually due to the length of insulin syringe needles, injections are therefore limited to the biceps for most persons.


While GHRP + GHRH can be injected each day with great benefit, even if you don't do weight training on that day. On the other hand, IGF-1 LR3 and MGF injections should be reserved for post-workout only.


Anti-Aging


For the Anti-Aging crowd, we recommend choosing only 1 peptide, rather than a combination. The reason for this is that as you get older your GH levels decline rapidly and therefore you will benefit from any kind of GH increase meaning there is no need to overdo things with multiple peptides. If you wish to use more than one peptide, we recommend cycling a GHRP product (GHRP-6, GHRP-2 or Ipamorelin) every 3-6 months with CJC-1295 DAC for two reasons.


The first reason is that CJC-1295 DAC is a GHRH (growth hormone releasing hormone) acting directly at the pituitary, while GHRP products indirectly stimulate GH by causing the release of Ghrelin. Rotating the products would therefore ensure one method of GH stimulation does not get "worn out" from repeated exposure to the peptides. The second reason is that even though CJC-1295 DAC has been proven safe in much higher dosages than we recommend, since it causes a continual GH release (GH bleed) no one can be certain how continual use would affect the pituitary in the long-term, so it's a case of being "better safe than sorry" and never using it for longer than 6 months at a time without a break.


Diet Considerations


For CJC-1295 DAC there are no particular diet restrictions that need to be followed due to its long half-life. For GHRP products the following should be observed as insulin and fatty acids can blunt the release of GH in the body and therefore make your injections less effective:
Avoid eating/drinking anything high in fat for 3 hours before your injection and anything high in carbohydrates for 1-2 hours (always do your injection on an empty stomach).
Wait at least 20 minutes after your injection before eating/drinking anything with calories.


Injection Amounts


CJC-1295 DAC taken at 2000mcg (2mg) once per week or;
GHRP Product (GHRP-2, GHRP-6 or Ipamorelin) taken at 200mcg per day.


Example Injection Routines


CJC-1295 DAC
2mg taken once per week, at any time of day.


GHRP-2, GHRP-6 or Ipamorelin


Example 1 - Night Time Injection (recommended to reduce possible tiredness during day).
Ensure you have an empty stomach (i.e. 2-3 hours since your last meal).
Inject your GHRP peptide and go straight to bed.


Example 2 - Morning injection
Take your injection of the GHRP product first thing in the morning at 100mcg.
Wait at least 20 minutes before having breakfast or any beverages (including coffee/tea).
(All info gathered via internet)

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Melanotan II possess anti-inflammatory response

Melanotan II possess anti-inflammatory response

Melanocortin Melanotan II possess anti-inflammatory response
« on: November 16, 2010, 1011 AM »

In Vitro and In Vivo Induction of Heme Oxygenase 1 in Mouse Macrophages following Melanocortin Receptor Activation
Connie W. Lam, Stephen J. Getting and Mauro Perretti2

The William Harvey Research Institute, Bart’s and the London, Queen Mary School of Medicine and Dentistry, London, United Kingdom

Abstract
RAW264.7 cell incubation with adrenocorticotrophin (ACTH) led to a time-dependent (4–24 h) and concentration-related (1–100 ng/ml) induction of heme oxygenase (HO)-1, and this was a specific effect, because the pattern of expression of other cellular proteins (HO-2, heat shock proteins 70 and 90) was not modified by ACTH. Combined RT-PCR and Western blot analyses revealed expression of the melanocortin receptor (MC-R) types 1 and 3, but not 4, in these cells. However, use of more selective agonists (including melanotan (MTII)) indicated a predominant role for MC3-R in the induction of HO-1 expression and activity. Relevantly, ACTH and MTII incubation with primary peritoneal macrophages (M{phi}) also induced HO-1 expression. The potential link between MC3-R dependent cAMP formation and HO-1 induction was ascertained by the following: 1) ACTH and MTII produced a concentration-dependent accumulation of cAMP in RAW264.7 cells, and 2) whereas a selective inhibitor of cAMP-dependent protein kinase A abrogated ACTH- and MTII-induced HO-1 expression, a soluble cAMP derivative promoted HO-1 induction both in RAW264.7 cells and primary M{phi}. HO-1 induction in peritoneal M{phi} was also detected following in vivo administration of MTII, and appeared to be functionally related to the antimigratory effect of this melanocortin, as determined with a specific inhibitor (zinc protoporphyrin IX). In conclusion, this study highlights a biochemical link between MC-R activation and HO-1 induction in the M{phi}, and proposes that this may be of functional relevance in determining MC-R-dependent control of the host inflammatory response.

Introduction
Melanocortin peptides (e.g., {alpha}-melanocortin-stimulating hormone) have long been reported to possess anti-inflammatory effects in many experimental models of acute and chronic inflammation, including inflammatory bowel disease (3), allergy (4), joint arthritis (5, 6), and systemic inflammation (endotoxemia) (7). Interestingly, recent trials with {alpha}-MSH have confirmed the positive indication for this compound in controlling human disease (Cool, thereby reinforcing the potential impact of this line of research. Because {alpha}-MSH represents the first 13 aa within the adrenocorticotrophin (ACTH) sequence (39 aa in total) (9), it is important to recall the efficacy of the longer polypeptide in controlling rheumatoid arthritis (10).

At the molecular level, the effects of these anti-inflammatory hormones and synthetic derivatives on target cells are brought about by activation of a subgroup of G protein-coupled receptor, termed melanocortin receptors (MC-R). Five MC-Rs have been identified so far, and all of these receptors are positively coupled to adenylate cyclase such that their activation leads to increases in intracellular cAMP (9, 11). Following this early event of cAMP formation, and also perhaps partly independently from it, melanocortin peptides have been shown to down-regulate NF-{kappa}B activation and consequent cytokine synthesis (12, 13). The C terminus sequence (i.e., aa 11–13) of {alpha}-MSH outside the common core and modifications of it (14, 15) have been shown to block cytokine functions (1), rather than synthesis and release (16).

Heme oxygenase (HO)-1 is the rate-limiting enzyme in heme catabolism with consequent generation of biliverdin (then converted to bilirubin), free iron, and carbon monoxide. Three mammalian HO isoforms have been identified, one of which, HO-1, is a stress responsive protein endowed with important cytoprotective effects (for a recent review, see Ref.17). In addition, macrophage (M{phi}) HO-1 expression is part of the repairing processes that occur during resolving inflammation leading to healing and tissue repair (18). It is possible that at least some of the cytoprotective and anti-inflammatory actions of HO-1 are due to the controlled local liberation of carbon monoxide, able to signal through the cyclic GMP pathway (17) and inhibit cytokine synthesis (19). In addition, the other catabolite bilirubin is also endowed with antioxidant and anti-inflammatory effects, for instance, its application inhibits LPS-induced selectin expression in the vasculature, thus affecting leukocyte recruitment (20).

The present study was undertaken to assess a potential functional link between MC-R-dependent cAMP formation and HO-1 induction in M{phi}. Most of the experiments have been conducted with the RAW264.7 M{phi} cell line, both for data consistency and ease of manipulation (and reduction in animal sacrifice); however, crucial experiments have been repeated with primary M{phi}. Importantly, in vivo experimentation not only confirmed the biochemical link between MC-R activation and HO-1 induction, but also provided a functional relevance to this interaction. We conclude that MC3-R activation, and possibly activation of other MC-R subtype as well, can bring about anti-inflammatory effects mediated, at least in part, by HO-1 induction.

Discussion
This study demonstrates a previously unknown link between M{phi} MC3-R activation and induction of the anti-inflammatory enzyme HO-1. Activation of this receptor by MTII, and the less selective agonist ACTH, produces transient alterations in intracellular cAMP that are temporally related to HO-1 up-regulation in a PKA-dependent fashion. In vivo, the MC3-R/HO-1 connection is functionally operative in bringing about the antimigratory effect of a melanocortin peptide.

Since the initial studies with {alpha}-MSH (27), melanocortin peptides have been shown to represent an important component of the counterregulatory systems that operate in the host to dampen and control the inflammatory reaction. Several studies conducted in experimental animals with models of acute and subacute inflammation (1, 28), in some cases supported by human data (29), have shown how {alpha}-MSH and other melanocortin peptides are endowed with potent inhibitory and anti-inflammatory properties (Cool. This field attracted much more interest once specific receptors were cloned and shown to mediate the actions of several melanocortins, including the naturally occurring ACTH and {alpha}-MSH, on different target cells. MC-R belongs to the family of G protein-coupled receptors, and their activation leads to adenylate cyclase-mediated conversion of ATP into cAMP (9, 11). Thus, accumulation of cAMP in target cells buffers cell activation with a marked effect on the production of proinflammatory cytokines (12, 13, 21). Therefore, targeting specific MC-R could certainly represent a novel strategy to develop innovative anti-inflammatory agents, as recently reviewed (30).

The similarity in mediated signaling events for the five MC-R can be problematic for drug development, impeding exploitation of specific postreceptor pathways: this aspect is made more acute by the absence of specific pharmacological tools to dissect the functions of each receptor. A few years ago, we started a project focusing on the resident M{phi}, reasoning that a certain degree of specificity could derive from narrowing down actions of a given target cell. Addition of ACTH, {alpha}-MSH, and the relatively more specific synthetic derivative MTII (31), to mouse peritoneal M{phi} inhibited the release of an array of cytokines and chemokines (21, 22). Comparison of the effects produced by agonists and antagonists, together with morphological analyses and study with mutated receptors, allowed us to pinpoint MC3-R as a major determinant for these inhibitory properties, at least at the level of the M{phi} (6).

MC3-R-mediated inhibition of cytokine synthesis and release from stimulated M{phi} in vitro occurs relatively rapid (≤2 h). In the present study, we set out to examine more delayed downstream events subsequent to MC3-R activation. RAW264.7 cells were used and initially validated for their expression of MC3-R message and protein. Confirming previous studies with monocytic cell lines (13, 32), RAW264.7 cells expressed MC1-R mRNA. However, we could not find the MC4-R mRNA, thus allowing us to use the mixed MC3/4-R agonist MTII (31) for most of the subsequent experiments. Because elevated cAMP levels have been associated with HO-1 induction in rat hepatocyte cultures (25), we monitored expression of this and other stress proteins in RAW264.7 cells following incubation with MTII or ACTH. Either peptide provoked a selective and marked up-regulation of HO-1 evident as early as 2–4 h postincubation: this effect was long lasting and fully evident even at the 24-h time point. In full agreement with the study on rat hepatocytes (25), MTII-mediated HO-1 induction was genuinely due to cAMP/PKA signaling, a fact that was confirmed also with primary M{phi} cultures. It is of interest that, during the preparation of this paper, a study showing ACTH induction of HO-1 in a mouse adrenocortical cell line was published (33). It therefore seems that activation of more than one MC-R (certainly MC3-R and MC2-R, the latter being selectively expressed in adrenal cells, and possibly all the other receptors) in target cells can lead to HO-1 up-regulation, thereby making this biochemical link a more general phenomenon. Subsequently, we investigated the potential functional consequences of this induction in experimental inflammatory settings.

In conclusion, this study indicates that HO-1 induction in M{phi} might be a major arm in the complex series of effects that are produced by melanocortin peptides acting at their MC-R. Our analyses on M{phi} function, in the present and previous studies, suggest that MC3-R is the major receptor determinant for transducing the anti-inflammatory actions of these peptides on M{phi}, although it is clear that we could also detect MC1-R in RAW264.7 cells, in analogy to Star et al. (32). However, irrespective of the specific MC-R, a more general picture is emerging in which MC-R activation on the M{phi} cell surface leads to cAMP formation and PKA activation. This signaling pathway produces at least two downstream events: inhibition of cytokine synthesis and release from stimulated M{phi} (in the presence of an inflammogen), which is evident within the first 2 h, and then up-regulation of HO-1 from ≥4 h post-MC-R activation. Importantly, the latter effect is achieved by the melanocortin peptide itself (i.e., in the absence of an inflammogen or M{phi} activator), suggesting that MC-R activation favors the acquisition of the anti-inflammatory proresolving phenotype by the M{phi} (a phenomenon originally described for glucocorticoids (40)). Fig. 8 schematizes this model of two hits, or anti-inflammatory mechanisms, activated by MC3-R agonists.

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