IGF-1 - The Hormone: Insulin-like Growth Factor-1
By MuscleTalk moderators mad_cereal_lover and POWERHOUSE585
This article is divided into two sections; firstly by mad_cereal_lover from scientific studies and individual user reports, and secondly through personal experience from POWERHOUSE585. This provides the reader with information on both sides of the spectrum. If you have questions for either author, please ask on the MuscleTalk Forum - (Other performance enhancing drugs section)
Section 1: IGF-1 - The Science - by MuscleTalk Moderator mad_cereal_lover
IGF-I and its actions in the body
IGF stands for Insulin-like Growth Factor, named so due to its structure being very similar to the hormone insulin, and is one of a group of hormones call somatomedins. Growth hormone (GH) and IGF-1 share many similarities in their modes of action, and this is in part due to the fact that binding of GH to certain GH receptors results in a signalling cascade that leads to the generation of IGF-1. It is through this route that GH exerts its proliferative (proliferation of cells basically means cell growth) effects1. Like GH, IGF-I enhances protein anabolism. Individuals who are normally fed and are administered both IGF-I and GH see no enhanced protein anabolic effect over either compound alone, however in calorie-deprived subjects, GH and IGF-1 appear to work synergistically to enhance a more positive protein balance2. The current trend of thought and research suggests that IGF-1 mediates the protein-anabolic actions of GH in humans3. IGF-1 also has properties including the transport of amino acids into cells and inhibition of protein degradation.
IGF-1 has been shown both in vitro and in vivo that it does not possess the lipolytic (fat mobilising) effects that GH exhibits, probably because there are no functional type-1 IGF-1 receptors found in adipocytes4. This may come as a surprise to many bodybuilders who seem to swear by the fat-loss properties of IGF-1 use; however it is highly unlikely that this arises through direct IGF-1 mediated lipolysis5.
With regards to carbohydrate metabolism, IGF-1 acts much like insulin (no surprise there), and administration of IGF-1 tends towards a hypoglycaemic (low blood sugar) state. Surprisingly though, this does not appear to be completely via the insulin receptor, but probably in addition by way of its own IGF-1 receptor6. IGF-1 is thought to be extremely important in the overall action of insulin on skeletal muscle7. IGF-1 results in improved insulin sensitivity, which is an important point to bear in mind for the bodybuilder who may already use or wish to use insulin. In other words, if you do use IGF-1 and you have not previously used insulin, don't start using it. If you are experienced with insulin and start to take IGF-1, insulin dosages may wish to be lowered as well as increased carbohydrate intake especially after insulin administration.
Use of IGF-1
IGF-1 is not a substance that inexperienced bodybuilders should consider using. Several years of anabolic steroid use is recommended before starting a course of IGF-1, and of course one must be aware of the hypoglycaemic effects of IGF-1. There are other serious risks that can occur with the use of IGF-I, such as increased risk of cancer, accelerated growth of tumours and enlargement of intestinal organs8, 9. For these reasons, it should be re-emphasised that for the inexperienced and novice bodybuilder, IGF-1 should not be taken lightly.
Due to the very short half-life of normal IGF-1 (<10mins) and its highly sensitive and unstable properties, plain (wild-type) IGF-1 is rarely used. Rather, an analogue of IGF-1 referred to as Long R3IGF-1 (LONG™R3IGF-1) is the preferred substance of choice. This analogue has had a substitution for the amino acid arginine (R) at position 3 (hence 'R3') for glutamine, and has been increased in length (hence 'long') by 13 amino acids. Basically these modifications to IGF-1 result in a peptide with lowered binding affinities for proteins that regulate IGF-1, thus increasing the potency of the IGF-1. The other advantage of Long R3IGF-I is its half-life being increased from minutes to several hours. Thus the user can get away using a much smaller amount of Long R3IGF-1 and administration does not have to be as frequent.
Dosages of Long R3IGF-1
Dosages of Long R3IGF-1 range from 20mcg up to 120mcg, although I would never recommend over 80mcg. A good starting point is 20-40mcg, however most start at 40mcg. Unlike GH, users report that the effects of Long R3IGF-1 are seen in a much shorter space of time, and a typical course length would be 4 weeks on, but some users go up to 50days on, 50days off. Many people use Long R3IGF-1 in combination with the end of a steroid cycle/beginning of and throughout post cycle therapy (PCT), and see increases in LBM as well as decreases in fat throughout this time. 1-2lbs of clean LBM every 2 weeks is not uncommon.
Long R3IGF-1 should be injected ideally post workout (PWO) on training days, although a morning/PWO split is also a good option. Long R3IGF-1 is best injected intramuscularly, and users often do this in a bilateral sense PWO in the muscle group just used, e.g. after training biceps one might inject 20mcg into one bicep and 20mcgs into the other. Injecting 5 days on, 2 days off is another common method employed. Although there is no direct scientific evidence of localised muscle growth, it has been suggested that IGF-1 receptors are upregulated specifically to the surface of cells that have undergone strenuous exercise, thus the reasoning for site-specific injections. Many users claim to see site-specific growth, however this as of yet cannot be validated as Long R3IGF-1's mode of action.
Side effects of Long R3 IGF-1 include in some cases severe headaches, nausea, possible hypoglycaemia and accelerated growth of existing tumours. For this reason I would discourage usage to anyone with a personal (or family) history of tumour growth/cancer.
Long R3IGF-1 is usually sold in either the lyophilised powder form, or already reconstituted form. There is much confusion as to how stable Long R3IGF-1 is once reconstituted, however unlike wild-type IGF-1, Long R3IGF-1 should be stable for several months once reconstituted even at room temperature, but ideally kept at 4oC, if not -20oC (manufacturers of Long R3IGF-1 recommend reconstitution in 100mM acetic acid to 1mg/ml and stored at -20oC for up to 3 months). This stability is dependent upon correct reconstitution with 100mM acetic acid. The concentration of Long R3IGF-1 is usually at 1mg/ml, thus 0.04ml would be required for 40mcg (4IU on an insulin needle). I know people who have used IGF-1 after having kept it reconstituted in acetic acid in the freezer for 1 year and still got great results. If this is a concern though, one can purchase the lyophilised form of Long R3IGF-1, which can be stored at 2-8oC, and reconstitute themselves, however bear in mind this reconstitution must be done with a sterile solvent and using sterile techniques. Finding the actual studies for this has proven to be somewhat troublesome, as they don't exist publicly, but rather we have to rely on the information given by GroPep on their website. NB: GroPep are the company that produce LongR3 IGF-1, and also own the patent (see www.gropep.com.au for more information):
How long is the stock solution stable for under these storage conditions?
Liquid stability data shows that Long R3IGF-1 is stable for 3 years (-20°C to 37°C). Therefore, the stock solution should be stable at 4°C for 3 years.
Is Long R3IGF-1 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.
Please note, that when GroPep state 'liquid stability' they are referring to LongR3 IGF-1 that has been reconstituted by their recommended techniques, i.e. 100mM acetic acid to a stock concentration of 1mg/ml. Some websites sell media grade Long R3 IGF-1 in both lyophilised and reconstituted form, with the latter being reconstituted according to GroPep's recommendations (100mM acetic acid). If you state in your order from some reputable companies that you would like some extra acetic acid, they usually include an extra 5ml or so for free, so you can dilute your solution further if desired.
Section 2: Personal Experiences of Long R3IGF-1 - by MuscleTalk Moderator POWERHOUSE585
NB: all references made to IGF from here on refer to the Long R3IGF-1 form of IGF-1
From my own personal experiences of IGF cycles I have seen no site-specific growth in any areas, although if used pre-workout the pumps from training the actual muscle the IGF was administered into are unbearable, something which I would seek to avoid. On another note it is said that many people who have used IGF have had no effects from it and in studies some have been known to be non-responders, irrespective it seems, of the dose administered. This is something one must consider when running such compounds. Another consideration to make when running IGF is the effectiveness of either receptor or media grade IGF. Receptor grade is way too expensive and has to be administered for effectiveness around 10-15 times per day.
- Media grade - 72% pure (use 3-4 weeks before antibody build-up)
- Receptor grade - 99% pure (use 4-8 weeks; little to no antibody build-up)
This is something to take into account when choosing your grade - in my opinion media is best and always will be for gains and convenience. As with anything, more is not always better with IGF, and more does not mean better protein binding effects. Also one must bear in mind that higher dosages will mean greater side effects, which are best avoided.
Many users have reported great gains from 20mcg every day combined with a good steroid cycle. It has also been suggested that once a user has completed an IGF cycle, subsequent cycles require increases in dosages. I for one and many others know this to have no truth whatsoever and be completely unfounded, and feel it is merely a fallacy suggested to facilitate greater source sales.
The products I have personally used are GenSci and GroPep, and I have found both to be very good. GroPep can be bought in larger amounts and reconstituted and used over longer periods thus using smaller amounts i.e. 20mcg every day, whereas GenSci's IGF is reconstituted using bacteriostatic water because they have secured the correct pH level required so as to not use complicated methods of reconstitution. This is beneficial for various reasons beyond the comprehension of the not-so-chemically-minded amongst us. However, it has a life of only 48 hours thus using the whole 100mcg bottle within that time frame. From personal experience I can tell you (and I am a high level user of performance enhancing drugs) that anything over 25mcg will result in extreme headaches. I for one suffer very badly having to use 50mcg every day.
IGF is best used when in a highly androgenic/anabolic state, and, as discussed in Section 1, works great when running PCT. Although I have seen many guys trying IGF after only a few years of steroid use, I find this a waste and a quick route which does not work; you still have to put the years of effort in! As for a cycle while using IGF, I suggest many years of constructive steroid use, and a solid nutrition and training regime under your belt. Please post on MuscleTalk for cycle advice while running IGF (as diet alterations will perhaps need to be considered as well).
Can IGF-1 be used with GH and is it any better?
There are so many studies and personal accounts out there so this is a not as clear-cut as one would hope. If using IGF with GH, then I tend to administer IGF morning and PWO, and HGH at night at around only 2IU. Remember that HGH also indirectly causes muscle growth by stimulating the release of IGF when it (the GH) is destroyed in the human body. Many people think running HGH with IGF is a waste of money for this same reason. So there is no definite answer.
- Greenhalgh, C.J. and Alexander, W.S. Suppressors of cytokine signalling and regulation of growth hormone action. Growth Horm IGF Res, 2004. 14(3): p. 200-6.
- Kupfer, S.R., et al., Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously. J Clin Invest, 1993. 91(2): p. 391-6.
- Butterfield, G.E., et al., Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women. Am J Physiol, 1997. 272(1 Pt 1): p. E94-9.
- DiGirolamo, M., et al., Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes. FEBS Lett, 1986. 205(1): p. 15-9.
- Hussain, M.A., et al., Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans. J Clin Invest, 1994. 94(3): p. 1126-33.
- Di Cola, G., M.H. Cool, and D. Accili, Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. J Clin Invest, 1997. 99(10): p. 2538-44.
- Yakar, S., et al., Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes, 2001. 50(5): p. 1110-8.
- Devi, G.R., et al., Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling. Growth Horm IGF Res, 2001. 11(4): p. 231-9.
- Steeb, C.B., J.F. Trahair, and L.C. Read, Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats. Gut, 1995. 37(5): p. 630-8.
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