Posted by: Mudge
From Harvery Baloner @ MC
(note some sources do carry it in vials now this article is a little outdated)
IGF stands for insulin-like growth factor. It is a natural substance that is produced in the human body and is at its highest natural levels during puberty. During puberty IGF is the most responsible for the natural muscle growth that occurs during these few years. There are many different things that IGF does in the human body; I will only mention the points that would be important for physical enhancement. Among the effects the most positive are increased amino acid transport to cells, increased glucose transport, increased protein synthesis, decreased protein degradation, and increased RNA synthesis.
When IGF is active it behaves differently in different types of tissues. In muscle cells proteins and associated cell components are stimulated. Protein synthesis is increased along with amino acid absorption. As a source of energy, IGF mobilizes fat for use as energy in adipose tissue. In lean tissue, IGF prevents insulin from transporting glucose across cell membranes. As a result the cells have to switch to burning off fat as a source of energy.
IGF also mimic's insulin in the human body. It makes muscles more sensitive to insulin's effects, so if you are a person that currently uses insulin you can lower your dosage by a decent margin to achieve the same effects, and as mentioned IGF will keep the insulin from making you fat.
Perhaps the most interesting and potent effect IGF has on the human body is its ability to cause hyperplasia, which is an actual splitting of cells. Hypertrophy is what occurs during weight training and steroid use, it is simply an increase in the size of muscle cells. See, after puberty you have a set number of muscle cells, and all you are able to do is increase the size of these muscle cells, you don't actually gain more. But, with IGF use you are able to cause this hyperplasia which actually increases the number of muscle cells present in the tissue, and through weight training and steroid usage you are able to mature these new cells, in other words make them grow and become stronger. So in a way IGF can actually change your genetic capabilities in terms of muscle tissue and cell count. IGF proliferates and differentiates the number of types of cells present. At a genetic level it has the potential to alter an individuals capacity to build superior muscle density and size.
There is a lot of talk about the similarity between IGF and growth hormone. The most often asked question is simply which is more effective. GH doesn't directly cause your muscles to grow, it works very indirectly by increasing protein synthesis capabilities, increasing the amount of insulin a person can use effectively, and increasing the amount of anabolic steroids a person can use effectively. GH also indirectly causes muscle growth by stimulating the release of IGF when it (the GH) is destroyed in the human body. So one way you could look at it as GH being a precursor to IGF. So to put it simple IGF is more effective at directly causing muscle growth and density increases. IGF is also much more cost effective.
IGF can also be effectively used by itself and gains will still be easily noticeable. With growth hormone you need to use high amounts of anabolics and often insulin to see any gains at all, this is not the case with IGF. IGF can be used by itself and is often used by bodybuilders who bridge between cycles, during this bridge is a good time to use IGF since it has no effect on natural testosterone production so it will therefore allow you to return to normal in terms of hormone levels. A stack of IGF, PGF2a, HCG, and clomid would be a good bridge stack and would allow your body to return to normal and still allow you to retain and make new gains.
IGF is a research drug, it hasn't been approved by the FDA for use as a pharmaceutical and it is currently being researched for nerve tissue repair, possible burn victims, and also as a possible aid in muscle wasting for AIDS patients. There are many different analogs of IGF available, instead of mentioning them all, I will simply mention the two most common and the most effective. Regular recombinant IGF is one of the two, it is also the more expensive and the least effective.
Regular IGF only has a half-life of about 10-20 minutes in the human body and is quickly destroyed, it can be combined with certain binding proteins to extend the half-life, but it is not a very simple procedure and there is a more effective and less expensive version available. The most effective form of IGF is Long R3 IGF-1, it has been chemically altered and has had amino acid changes which cause it to avoid binding to proteins in the human body and allow it to have a much longer half life, around 20-30 hours. "Long R3 IGF-1 is an 83 amino acid analog of IGF-1 comprising the complete human IGF-1 sequence with the substition of an Arg(R) for the Glu(E) at position three, hence R3, and a 13 amino acid extension peptide at the N terminus. This analog of IGF-1 has been produced with the purpose of increasing the biological activity of the IGF peptide."
"Long R3 IGF-1 is signifacantly more potent than IGF-1. The enhanced potency is due to the decreased binding of Long R3 IGF-1 to all known IGF binding proteins. These binding proteins normally inhibit the biological actions of IGF's."
It is also not as expensive since a media grade version is available which is sufficient for bodybuilding use. There is also a receptor grade available but it is VERY expensive and the only noticeable difference between the two would only be able to be noticed in a laboratory setting. The price on the black market for Long R3 IGF-1 can be seen anywhere from $300-$500 per milligram depending on the source, be wary of black market ******s of any IGF since it is a VERY difficult item to obtain. As mentioned IGF is a research product and is only available from a few laboratories in the world and is only available to research companies and biotechnology institutions. For the rest of this article when I say IGF I am now referring to Long R3 IGF-1 for simplicity sake.
Any form of IGF is ONLY supplied in a lyphosized form, which means a dry powder state. NEVER PUCHASE PRE-DILUTED LIQUID IGF!!!! There is no such product made anywhere in the world and even if there were real IGF ever present in the vial it would all be dead by the time you receive it. IGF is a very delicate peptide and must be diluted by yourself, where you have access to a refrigerator and freezer. There has also been a lot of talk by certain sources claiming to have IGF made by the Eli Lilly company, to clear things up Lilly is a pharmaceutical company and as stated IGF is a research drug and has not yet been approved, Lilly does not and never has manufactured research drugs for retail sale.
The dilutents you will need for the IGF are a weak concentration of hydrochloric acid and a sterile buffer(sterile water or bacteriostatic water) the procedure for diluting the IGF is not very difficult, the dilutents can be obtained from most local chemical suppliers and a good source of IGF would also be able to supply the necessary dilutents.
The most effective length for a cycle of IGF is 50 days on and 20-40 days off. The most controversy surrounding Long R3 IGF-1 is the effective dosage. The most used dosages range between 20mcg/day to 120+mcg/day. IGF is only available by the milligram, one mg will give you a 50 day cycle at 20mcg/day, 2mg will give you a 50 day cycle at 40mcg/day, 3mg will give you a 50 day cycle at 60mcg/day, 4mg will give you a 50 day cycle at 80mcg/day and so on. The dosage issue mainly revolves around how much money you have to spend, plenty of people use the minimum dosage of 20mcg/day and are happy with the results, and in fact several top bodybuilders use the 20mcg/day dosage and are pleased with the results. IGF is most effective when administered subcutaneously and injected once or twice daily at your current dosage. The best time for injections is either in the morning and/or immediately after weight training.
Another frequently asked question of IGF refers to the real world results, in terms of pure weight gain don't expect to gain 5 lbs. a week like you may off of anadrol or a similar steroid. The only weight you will gain from IGF use is pure lean muscle tissue, with steroids most of the weight gained is water weight. With an effective dosage you can expect to gain 1-2 lbs of new lean muscle tissue every 2-3 weeks and these effects can be increased with the use of testosterone, anabolic steroids, and insulin use. Increased vascularity is also very common, people report seeing veins appear where they never have before. And yet another effect reported is the ability to stay lean while bulking with heavy dosages of steroids and TONS of food while on an IGF cycle, this is perhaps the most pleasing effect. Increased pumps are also noticeable almost immediately, the pumps can almost become painful, pumps are even noticeable when doing cardio.
Overall, IGF is a very exciting drug due to its ability to alter ones genetic capabilities. If you can find a trustworthy source and you use it correctly it can be a VERY useful tool in your bodybuilding drug arsenal
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From Scorpio @ MC -
IGF-1: How does it work?
To understand how IGF-1 works you have to understand how muscles grow. The ability of muscle tissue to constantly regenerate in response to activity makes it unique. It’s ability to respond to physical/mechanical stimuli depends greatly on what are called satellite cells. Satellite cells are muscle precursor cells. You might think of them as "pro-muscle" cells. They are cells that reside on and around muscle cells. These cells sit dormant until called upon by growth factors such as IGF-1. Once this happens these cells divide and genetically change into cells that have nuclei identical to those of muscle cells. These new satellite cells with muscle nuclei are critical if not mandatory to muscle growth.
Without the ability to increase the number of nuclei, a muscle cell will not grow larger and its ability to repair itself is limited. The explanation for this is quite simple. The nucleus of the cell is where all of the blue prints for new muscle come from. The larger the muscle, the more nuclei you need to maintain it. In fact there is a "nuclear to volume" ratio that cannot be overridden. Whenever a muscle grows in response to functional overload there is a positive correlation between the increase in the number of myonuclei and the increase in fiber cross sectional area (CSA). When satellite cells are prohibited from donating new nuclei, overloaded muscle will not grow (Rosenblatt,1992 & 1994; Phelan,1997). So you see, one important key to unnatural muscle growth is the activation of satellite cells by growth factors such as IGF-1.
IGF-1 stimulates both proliferation (an increase in cell number) and differentiation (a conversion to muscle specific nuclei) in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. This is in agreement with the Dual Effector theory. In fact, you can inject a muscle with IGF-1 and it will grow! Studies have shown that , when injected locally, IGF-1 increases satellite cell activity, muscle DNA content, muscle protein content, muscle weight and muscle cross sectional area (Adams,1998).
On the very cutting edge of research scientists are now discovering the signaling pathway by which mechanical stimulation and IGF-1 activity leads to all of the above changes in satellite cells, muscle DNA content, muscle protein content, muscle weight and muscle cross sectional area just outlined above. This research is stemming from studies done to explain cardiac hypertrophy. It involves a muscle enzyme called calcineurin which is a phosphatase enzyme activated by high intracellular calcium ion concentrations (Dunn, 1999). Note that overloaded muscle is characterized by chronically elevated intracellular calcium ion concentrations. Other recent research has demonstrated that IGF-1 increases intracellular calcium ion concentrations leading to the activation of the signaling pathway, and subsequent muscle fiber hypertrophy (Semsarian, 1999; Musaro, 1999). I am by no means a geneticist so I hesitated even bringing this new research up. In summary the researchers involved in these studies have explained it this way, IGF-1 as well as activated calcineurin, induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor nuclear factor of activated T cells or NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signaling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs leading to increased contractile protein synthesis and muscle hypertrophy. Did you get all that?
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From Scorpio @ MC - (kinda shows something bout the strength)IGF-1 Once Again Proves to be One of the Most Powerful Mediators of Muscle Growth-by Bryan Haycock, MS, CSCS
Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function
Researchers:
Elisabeth R. Barton-Davis*, Daria I. Shoturma*, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney*,
* Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA and Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA
Source:
Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7
Summary:
Although the mechanisms underlying age associated muscle loss are not entirely understood, researchers attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers.
They demonstrated that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice (Figure 1), and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles (Figure 2). Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. These results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated.
Discussion:
I’m not sure where to begin. This study has the potential to completely change the way we age.
In this experiment, a recombinant adeno-associated virus, directing overexpression of insulin-like growth factor I (IGF-I) in mature muscle fibers, was injected into the muscles of mice. The DNA that was originally in the virus was removed along with markers that stimulate immune response. DNA coding for IGF-1 was then put into the virus along with a promoter gene to ensure high rates of transcription. The results, as you can see by figures 1 & 2, were dramatic.
IGF-1 plays a crucial role in muscle regeneration. IGF-1 stimulates both proliferation and differentiation of stem cells in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. IGF-1, when injected locally, increases satellite cell activity, muscle DNA, muscle protein content, muscle weight and muscle cross sectional area. The importance of IGF-1 lies in the fact that all of its apparent functions act to induce muscle growth with or without overload although it really shines as a growth promoter when combined with physical loading of the muscle.
IGF-1 also acts as an endocrine growth factor having an anabolic effect on distant tissues once released into the blood stream by the liver. IGF-1 possesses the insulin-like property of inhibiting degradation, but in addition can stimulate protein synthesis. The insulin-like effects are probably due to the similarity of the signaling pathways between insulin and IGF-1 following ligand binding at the receptors.
The ability of IGF-I to stimulate protein synthesis resembles the action of GH, which was shown in separate studies on volunteers to stimulate protein synthesis without affecting protein degradation. Although it is often believed that the effects of GH are mediated through IGF-1, this cannot be the case entirely. First, the effects of the two hormones are different, in that GH does not change protein degradation. Second, the effect of GH is observed with little or no change in systemic IGF-1 concentrations. Age related muscle loss has been prevented with GH injections, however it is believed that this is accomplished through IGF-1.
The results of this study are similar to other studies where IGF-1 was injected directly into muscle tissue, resulting in increases in size and strength of experimental animals. Using a virus as a genetic vehicle has an advantage over simply injecting the growth factor. The effects of a single viral treatment last significantly longer (months if not years) because the muscle cell itself is constantly overproducing its own IGF-1 from injected DNA.
The fact that the IGF-1 produced by the muscle of these mice did not reach the blood stream is interesting. Systemic injections of IGF-1 have not been successful in inducing this kind of anabolic effect in humans. In addition, IGF-1 produced by the liver is genetically different than that produced by muscle tissue. It could be that providing additional DNA for the muscle to produce it’s own IGF-1 is the key to achieving anabolic and rejuvenative effects specifically in skeletal muscle.
In this study there was a preferential preservation of type IIb muscle fibers in aging mice. These are the fibers most sensitive to muscle hypertrophy from training and they are also the first fibers to disappear with aging. In the mice receiving the engineered virus, there was also a preservation of the motor neuron, leading to an increase in functional capacity. It is speculated that age related muscle loss is secondary to the loss of neuronal activation of type-II fibers. By preventing the degeneration of typ-II motor units, functional capacity could be maintained into old age. This technique may also serve useful in the prevention of osteoporosis. Further study is necessary to determine wether IGF-1 is having an effect only on muscle fibers or on nervous tissues as well.
Finally, it was also exciting to see muscle growth in the young mice who received the injection (15% increase in muscle mass). This means that the injection provided levels of IGF-1 far and above what the muscle normally has access to and not simply a preservation of normal levels. Remember that this was not combined with exercise. The growth of the injected muscles happened even without an extreme mechanical stimulus. The mice were simply allowed to run around as they usually do. Because of these dramatic results, the authors expressed concern about the use of this technique to enhance performance or cosmetic appearance. Research Update is not my personal soap box so I won’t go off on the gender centered hypocrisy of cosmetic enhancement in our society. All we can hope for is that this technique will be used to treat more important diseases such as muscular dystrophy and thereby become somewhat available for other uses as well.
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From Dr JMW @ AS (info +personal expeirinece)
· Long™R3IGF-I is an analog of human IGF-I.
· It is a superior alternative to insulin in serum-free media.
· It increases protein production by cells in culture medium.
· It increases cell viability by inhibiting apoptosis.
· It has a longer half-life in cell culture than insulin.
· It is readily available.
· There is secure and ample manufacturing capacity at GroPep Limited.
· No animal- or human- derived material is used in the manufacture or storage of Long™R3IGF-I.
· Long™R3IGF-I is already being used in the manufacture of three (3) biopharmaceuticals approved by FDA and EMEA.
Frequently Asked Questions
What cell types will respond to Long™R3IGF-I?
All cells that have a Type I IGF receptor will potentially respond. Most commercially used cells including CHO, fibroblasts and hybridomas have a type I IGF receptor. All cells which respond to pharmacological concentrations of insulin (>1 mg/liter) will respond to Long™R3IGF-I (10-50 mg/liter).
Is storage of the stock solution at 4°C acceptable?
Yes
How long is the stock solution stable for under these storage conditions?
Liquid stability data shows that Long™R3IGF-I is stable for 3 years (-20°C to 37°C). Therefore, the stock solution should be stable at 4°C for 3 years.
What type of preparation is available?
Liquid formulation, preferable for GMP production.
Freeze dried preparation.
Is Long™R3IGF-I stable?
Re-test date for freeze-dried peptide is 3 years. Liquid formulation stability studies have recently been completed. It is stable for 3 years (-20°C to +37°C). We have data indicating stability in media at 4°C for 1 year.
Here is an article written by a self-experimenter.
December 15, 2000
Answer: What a perfect question! You actually have talked to just the right person. I have a business associate that worked for the company that produces this in Australia. Several years ago, I ordered 10mg of Long R3 IGF-1 and used it for several months. What I found out was truly amazing.
Before I tell you about my results, let me tell you that if you are going to use IGF-1 then make sure it is the Long R3 version! Let me explain. Regular IGF-1 like what is produced in your body is transported around connected to binding proteins. There are quite a few of these and their main purpose is to grab ahold of the IGF-1 peptide and keep it from being quickly degraded. Without these binding proteins, all of the IGF-1 would be metabolized in the body within a few minutes. The problem (at least it seems like a problem but might actually be a good thing) is that these binding proteins basically prevent the IGF-1 from performing its function. As long as IGF-1 is attached to the binding protein it cannot do the cool stuff that it wants to do. Regular IGF-1 must be released from its binding protein in order to accomplish its mission. Part of the problem is that much of the IGF-1 is degraded before it is released (seems like much is wasted doesn’t it?)
With Long R3 IGF-1 this problem doesn’t exist. Understand that the Long R3 version does not bind to the various binding proteins. It is free to move throughout your body and immediately start doing all the cool stuff that it wants to do. Again, understand that the Long R3 version is several orders of magnitude stronger than regular IGF-1.
If you would happen to use regular IGF-1, you would need several milligrams per day in order to get the desired effect. With the Long R3 version, you need only microgram quantities. Long R3 is also inherently MUCH cheaper to produce. What I am saying is that for the average person, regular IGF-1 is not practical-it is too expensive and you need to use too much. With Long R3 IGF-1, the price to results ratio is pretty good!
Something else I want to explain is how I went about preparing it for injection into my body. Unfortunately, this is not easy and the average person will have a hard time doing it. At the time, I worked in a sophisticated lab which had all of the necessary equipment. I ordered 10mg of Long R3 IGF-1 and it came in a single flip-top vial. 10mg might not seem like much but believe me, when it comes to Long R3 IGF-1, it is a ton! Some people might say to just add saline to the vial, keep it in the fridge and inject it when necessary. However, this will not work well because the IGF-1 is not highly stable and will degrade in an aqueous environment. 10mg was enough for many months and I needed a way that would allow the IGF-1 to remain potent during this entire time. I did my research and developed my method. I ordered what is known as microvials and sterilized them. I then diluted the IGF-1 with sterile water and added just a tad of acid to increase stability. Although it took quite a while, I then used a micropipette and alliquotted an amount of solution that contained 50mcg into one of my microvials. I closed the microvial and then froze it in a deep freezer. When I was ready to inject, I took out one or more of my microvials, thawed it out, combined it with saline and injected it.
When I first started taking Long R3 IGF-1, I used 50mcg every other day. Amazingly, within days, I started noticing some effects in my body. I felt super hungry all of the time and just felt “anabolic”. I can’t describe this feeling except to say that it was very similar to being on anabolic steroids (I wasn’t on at the time). Within one month, I gained almost 17 pounds of fairly lean mass! After the first month, something happened though and I noticed that it didn’t seem to be working that well. I upped the dosage several times over the next month to keep up the desired effects. On the third month, I was using several hundred micrograms per day but wasn’t noticing any further gains. All in all, I gained about 20 pounds of pretty solid mass!
Please notice that almost all of my gains were within the first month of taking the Long R3 IGF-1. After this first month, my gains slowed down considerably and eventually stopped altogether even though I was taking high dosages. Why did this happen?
From all of my research.......I suppose one of two things might have happened to prevent me from making further gains. What I truly suspect is that the Long R3 IGF-1 downregulated the amount of binding proteins being produced by my body (research confirms this). When I first started to inject the IGF-1, I was supplementing my own body’s IGF-1. I not only had my own IGF-1 working throughout the day but I had the potent surges of Long R3 IGF-1 that I would inject. Over time though, the binding proteins were downregulated. Of course my body continued to produce some (albeit less) IGF-1, however, because there were very little or no binding proteins it was quickly degraded. From what I can tell, I was in a state where 95% of the day my body did not have the benefits of IGF-1. Basically, it got what it got when I injected the Long R3 version.
The other possibility is that I built up antibodies to the Long R3 IGF-1 which basically sought out and destroyed what I injected. Although possible, I don’t believe this actually happened because it is not supported by research. I have seen no evidence which suggests that Long R3 IGF-1 causes antibody production.
To fix the above problem, one would have to cycle the Long R3 IGF-1. The best thing would probably be to take it every other month. This would allow your own body’s IGF-1 and binding proteins to return to normal.
Overall....I had a good experience with Long R3 IGF-1. The results were different than with steroids. I have noticed that steroids cause preferential growth of certain muscles, especially those that are stressed (as in lifting). The IGF-1 though seemed to cause my entire body to get a little thicker. I guess IGF-1 is less compensatory in nature and exerts a more whole-body anabolicity.
Would I recommend IGF-1? To the right person who is very careful and knows what he’s doing and has a good background in the sciences and has access to a good lab, YES! However, you can tell that I have listed many prerequisites to using it. For the average Joe, I believe is is just too complicated to be safe.
*note, it can be found for $200 a mg or even $1000 for 10mg if you shop around.
