# IGF-1 Manual



## PRIDE (Nov 3, 2011)

*Introduction*

IGF-1 isn't new. All mammals make IGF-1 and would die without it. IGF-1 secretion in the human body can be thought of as belonging to two separate, broad categories: Autocrine and Paracrine. While there are many versions of IGF-1 in the body, these are the broad categories that need to be understood in order to know exactly what you are doing when supplementing IGF-1. This thread focusses on practical application rather than pure science, as most IGF-1 researchers reading this material are bound to have more interest in actual effects of the product than its chemistry or whatnot.

*Firstly, definitions*

Autocrine: An IGF-1 molecule that is expressed by the cell for use within itself is known as autocrine IGF-1. This IGF is only active within the cell itself and on its surface. AAS increase the expression of IGF-1 by muscle cells. Cancerous tumors, for example, express autocrine IGF-1 much more than normal cells, and that is one factor of their unnaturally accelerated growth, division and multiplication.

Paracrine: Also known as systemic IGF-1, this molecule is synthesized by the liver. Its synthesis is rate-limited by the availability in the liver of both insulin and growth hormone and is the main reason for the widely known synergy between insulin and hGH administration. This IGF-1 acts differently than the autocrine and it effects every organ in the body. It is also the main vector of effects of hGH administration, meaning that most of the effects gained by hGH administration can also be gained by directly administering IGF-1. All IGF-1 administration is of the paracrine type.

IGFBP: This is a binding protein that plays much the same function to IGF-1 as SHBG, or sex hormone binding globulin plays to testosterone and estrogen. A binding protein holds on to its target molecule, temporarily inactivating it. The dynamics of IGFBP are somewhat complex, but let it be known that IGFBP is sort of a nemesis to IGF-1 since it renders it inactive.

Long R3 IGF-1: I will spare you the boring details of why it is called Long R3 and rather go into how it is functionally different from the natural form. The normal IGF-1 molecule has a very short half-life, approximately 20 minutes. It is either taken up by IGF-1 receptors on cells, or inactivated by IGFBPs. This is the reason why people injected huge amounts of many mg every day of IGF-1 15 years ago, whereas today the normal dose in a few dozen micrograms. What happened? Someone modified the natural IGF-1 molecule just enough that it would retain all its good properties and yet would resist being bound by IGFBPs. This is the Long R3 form of IGF-1. This is what you buy, practically no one tries to sell the natural form anymore. This has a half-life of about 12 hours.

Media Grade: This is the more usual grade of Long R3 IGF-1 that you see on the market. It is about 95% pure IGF-1 with some other incomplete peptides in it. And since the dose of IGF-1 is so small, the maximum 5% impurities of media grade represent a truly tiny amount. And the meaning of impurities in this context is simply some amino acids, either loose or in peptide form. In all likelihood that 5% of non-IGF-1 peptides is truly harmless.

Receptor Grade: Receptor-grade IGF-1 is guaranteed to be at least 99% pure Long R3 IGF-1 peptide. This grade is only used in advanced human trials in very specific spots on the planet. It is a truly rare thing and does not offer the bodybuilder any real-life advantage over media grade. It is also unavailable. There has been batches of some substance sold as "Receptor grade IGF-1" over the last year or so and here a very serious warning must be given. There is a peptide which is only the receptor binding portion of the IGF-1 molecule, which is a cellular lab product which contains bovine peptides and prions. This stuff has no other function than to bind to the IGF-1 receptor. It has no beneficial properties but blocks the receptor from being used by actual IGF-1. Some very bad or misinformed people have been selling this to bodybuilders as receptor grade IGF-1. This stuff can be very toxic. Prions cause CNS trouble of which mad cow disease is an example.

AA: Short for Acetic Acid, a commonly-used solvent for diluting the IGF-1 powder. This is said to keep the fragile IGF-1 molecule more stable than other solvents. This point is heavily debated. AA is an acid and it tends to kill whichever tissue you inject it into. It is best to dilute the IGF-1 with as little AA as can be done, and then to dilute this solution again when injecting so as to damage the target tissue as little as possible.

BW: Bacteriostatic water. This is simply purified water mixed with 0.9% Berylic Alcohol. Microorganisms cannot survive in this water. It is a very common solvent for injections and should be easily obtainable even from your local drugstore. BW is not an ideal solvent for long-term IGF-1 solution and storage as it tends to degrade much more quickly in BW than in AA. Again there is much debate as to how quickly IGF-1 does degrade in BW.

*Secondly, Effects*

Muscle satellite cell prolferation is the single most important effect of IGF-1 to us bodybuilders. In order to perfectly understand what this means, we must examine how muscles grow.

Muscle grows in two ways: the amount of contractile protien inside a fiber increases, which increases muscular strength and the space taken up by that additional strand of protein is added lean body mass. This is a comparatively small amount of size, but a lot of strength. The second way that muscles grow is when satellite cells merge with real muscle cells and donate their nucleus. Satellite cells have only one nucleus. And muscle cells, unlike the other cells in the human body, have at least one nucleus, without a set ceiling to how many there can be.

Myonucleii are the parts of the cell that are responsible for protein synthesis and expression. Whenever you damage a muscle through training, the rebuilding process that ensues is accomplished mostly by the myonucleii, which make new contractile protein which is used to repair and when possible upgrade the muscle cell's ability to generate and withstand force. Moreover, the size of a muscle cell is directly proportional to its myonuclear number, i.e. the number of nucleii that the cell contains. So the maximum amount of carbohydrate, water, minerals and protein that a muscle cell can absorb and retain are all dependent on ONE thing: the myonuclear number.

Moreover, the ability to recover (and upgrade) from damage is also proportional to the myonuclear number. As such, having high myonuclear numbers should be on top of every bodybuilder's priority list. Now how do we get the satellite cells to donate their nucleii? Interestingly, it is the autocrine IGF-1 that signals adjacent satellite cells to donate their myonucleii. Autocrine IGF-1 expression happens with exercise and is proportional to many things, including the level of androgen receptor stimulation. Yes this means that one of the ways in which anabolic steroids help growth is through the added expression of autocrine IGF-1 and merging of satellite cells.

One very interesting theory of steroids is that the decreasing results from successive cycles, which have absolutely nothing to do with receptor downregulation, actually has more to do with having merged more and more of the satellite cells into the muscles and having less and less new satellite cells for merging and donation puposes.

As you guessed, exogenous IGF-1 administration fixes this splendidly by its potent stimulation of satellite cell hyperplasia. Hyperplasia pulls a lot of carbohydrate and protein from the bloodstream to make new cells. This also requires a very large amount of energy, which can be obtained from burning fats, since the energy expenditure is not extremely rapid. The low blood glucose that ensutes IGF-1 administration as well as greatly increased triglyceride metatolism on the part of the dividing myoblasts compound to generate a substantial fatloss effect.

When injected, IGF-1 floats around until it finds an IGF-1 receptor or another binding site such as the IGFBP. Of course for the usual Long R3 form that most use, the IGFBP is not a factor and the IGF molecule will just wander until it finds a receptor. Exercise upregulates the trained muscle's receptor, bringing it to the cell's surface and "opening" it for business with an IGF-1 molecule. Once IGF-1 binds to that site, it will be absorbed by the cell and metabolized. One IGF-1 molecule can only trigger one receptor. Obviously, we want to target muscle receptors, as all other cell types also have IGF-1 receptors. Skin & hair follicles, sure why not. What you want to avoid growing are bones, internal organs such as intestines, and tumors. Interestingly, the highest concentration of IGF-1 receptors are in the gut.

*Thirdly, usage*

This is where stuff gets somewhat debatable. Best IGF-1 treatment protocol isn't a science yet. It is nowhere close to the state of advancement that AAS use has attained, and there will be much argument as to which protocol is best. Still, I will attempt to give an objective, wide-ranging set of available options for the IGF-1 researcher.

For a good while now, it has been found that a dose of 40mcg divided in bilateral administration in the muscles trained gave good results. It has been found that after 30 to 40 days of such a protocol, results diminish and stop. From this fact has stemmed an effective protocol recommending 30-day cycles of 40mcg daily IGF-1 bilateral intramuscular administration, followed by 30 days off. This works, no doubt about it. Most users prefer cycles of 25 days on, 25 days off since the 40mcg dose will use up one miligram in a cycle. IGF-1 receptors seem to downregulate proportionally to the dosage used.

Some people have tried 80mcg with a greater immediate response. I have seen up to 200mcg daily administration and of course short-term effects are proportional to the dosage administered. Some people find that they get a better pump when injecting the IGF-1 preworkout. Others feel that IGF-1 should be something more than a simple pump product and use it postworkout in an attempt to generate as much mitosis of myoblasts as possible.

Based on the science posted above about IGF-1 biochemistry and effects, the following points stand out as a base to fashion a good IGF-1 treatment protocol. Firstly, the most important effect to be sought is myoblast mitosis, as ONLY IGF-1 can achieve this effect, arguably the single most important thing for bodybuilding. Anything else should be seen as a bonus. Secondly, you want to use just enough IGF-1 to initiate mitosis in the target muscle and avoid spillover of the peptide to systemic distribution where probability says it will grow your guts instead of your muscles. This stuff is far from free and "GH guts" are far from aesthetic. Thirdly, you want this quantity of IGF-1 to be in as small a volume of liquid as practical. Fourthly, you want to administer the IGF-1 immediately postworkout when the receptors are maximally stimulated. Any other administration timing is suboptimal.

Now because IGF-1 treated cells leech glucose from the bloodstream like crazy, it is possible to go into hypoglycemia from IGF-1 supplementation. Feed carbs steadily from the time of the injection up until about 6-8 hours afterwards or whenever glycemia stabilizes. This is effect is dose-dependent.

*Fourthly, Storage*

*Study conducted by Gropep

The stability of a liquid solution of LR3IGF-I was monitored for a period of two years at storage conditions of -20 C, +4 C, +22 C, and +37 C. The final concentration of LR3IGF-I was in acetic acid. At various time points, samples were taken and compared to a lyophilized control (stored at 4 C). Listed below are the stability results for each respective storage condition.

Storage Condition: -20 C (-4 F)
Biological Potency No Change up to 2 years
Immunological Activity No Change up to 2 years
Mobility of Protein No Change up to 2 years
Elution Profile by reversed phased HPLC No Change up to 2 years

Storage Condition: +4 C (39.2 F)
Biological Potency No Change up to 2 years
Immunological Activity No Change up to 2 years
Mobility of Protein No Change up to 2 years
Elution Profile by reversed phased HPLC No Change up to 2 years

Storage Condition: +22 C (71.6 F)
Biological Potency No Change up to 2 years
Immunological Activity No Change up to 2 years
Mobility of Protein No Change up to 2 years
Elution Profile by reversed phased HPLC No Change up to 2 years

Storage Condition: +37 C (98.6 F)
Biological Potency No Change up to 1 year
Immunological Activity No Change up to 1 year
Mobility of Protein No Change up to 1 year
Elution Profile by reversed phased HPLC No Change up to 1 year

In conclusion, there is no significant difference in the potency of LR3IGF-I associated with the storage of the liquid formulation when stored at this range of temperatures. There is no evidence for loss of biological activity at any of the tested temperatures when stored as a liquid product. As you can see IGF can be quite stable for even a year at room temperature, but if you want to keep it around for a while then stick it into the fridge. So the best way to store LR3 that is suspended in BA (benzoic acid) is in the freezer. The BA won’t allow it to freeze. And if you have it suspended in AA (acetic acid), store it in the fridge.


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