03-29-2006, 06:13 PM #1
Mechano Growth Factor (MGF) and Insulin-Like Growth Factor-1 (IGF-1) Information
Mechano Growth Factor (MGF) and Insulin -Like Growth Factor-1 (IGF-1)
LakeMountD (*************.com member)
What is MGF?
Muscle satellite cells are mononuclear cells that remain in a quiescent state until activated when they proliferate and fuse with muscle fibers to donate nuclei, a process necessary for post-embryonic growth, hypertrophy and tissue repair in this post-mitotic tissue. These processes have been associated with expression of the insulin-like growth factor (IGF-I) gene that can undergo alternative splicing to generate different gene products with varying functions. To gain insight into the cellular mechanisms involved in local tissue repair, the time courses of expression of two IGF-I splice variants produced in muscle were determined together with marker genes for satellite cell activation following local muscle damage. Using real-time RT-PCR with specific primers, the mRNA transcripts in rat tibialis anterior muscles were measured at different time intervals following either mechanical damage imposed by electrical stimulation of the stretched muscle or damage caused by injection with bupivacaine. It was found that the autocrine splice variant mechano growth factor (MGF) was rapidly expressed and then declined within a few days following both types of damage. Systemic IGF-IEa was more slowly up regulated and its increase was commensurate with the rate of decline in MGF expression. Satellite cell activation as measured by M-cadherin and one of the muscle regulatory factors MyoD and the sequence of expression suggests that the initial pulse of MGF is responsible for satellite cell activation, as the systemic IGF-IEa mRNA expression peaks after the expression of these markers, including M-cadherin protein. Later splicing of the IGF-I gene away from MGF but towards IGF-IEa seems physiologically appropriate as IGF-IEa is the main source of mature IGF-I for up regulation of protein synthesis required to complete the repair.
What is insulin-like growth factor (IGF-1)?
The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF "axis) consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (IGF-I and IGF-II), a family of six high-affinity IGF binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzymes, referred to collectively as proteases. This system is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer. The IGF axis has been shown to play roles in the promotion of cell proliferation and the inhibition of cell death (apoptosis). IGF-II is thought to be a primary growth factor required for early development while IGF-I expression is seen in later life. Gene knockout studies in mice have confirmed this though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily fetal in action it is also essential for development and function of organs such as the brain, liver and kidney.
Insulin-like growth factor 1 (IGF-1) is mainly secreted by the liver as a result of stimulation by growth hormone (hGH). Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs. In addition to the insulin-like effects, IGF-1 can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis.
IGF-II is secreted by the brain, kidney, pancreas and muscle in mammals. It is more specific in action than IGF-1. In adult humans it is found at 600 times the concentration of insulin.
IGF-1 and IGF-II are regulated by a family of genes known as the IGF-Binding Proteins. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are 6 characterized IGF Binding Proteins (IGFBP1-6). There is currently significant data suggesting that IGFBPs play important roles in addition to their ability to regulate IGFs.
Studies of recent interest show that the IGF axis plays an important role in aging. Nematodes, fruit-flies and other organisms have an increased life span when the gene equivalent to the mammalian IGF is knocked out. Clearly the IGF/Insulin axis has an ancient evolutionary origin. Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.
Further work is required to determine the main receptors used by these growth factors to elicit their effects. Currently the IGF's are known to bind the insulin receptor, IGF-1 receptor, IGF-2 receptor, the insulin-related receptor and possible other receptors. IGF-1 and IGF-2 strongly bind to and activate the IGF-1 receptor, with weaker binding and action occurring through insulin receptors. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor" - it activates no intracellular signaling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signaling.
Theoretical Dosing Protocols / Stacks
(Written by LakeMountD)
There are many various types of MGF, MGF+IGF-1, IGF-1 stacks that have been attempted and although many of them have been successful, there hasn’t, yet, been a standalone winner. This is due to many factors including availability, price, and little experimental evidence on topics such as down regulation of receptors, antibody production, and suppression of natural hormones/growth factors. There are a lot of people on various boards attempting to “figure out” the scattered scientific data that is spread throughout the internet but it is doing only a small amount of good since most studies conducted on MGF and IGF-1 are done on rats and almost all of the studies done using IGF-1 use the naturally occurring IGF-1. There are a lot of doctors and users who question the safety of exogenous IGF-1 use, however. The prime reason surrounding this questionability is due to the fact that IGF-1 has been shown to increase the growth rate of cancerous tumors. It must be noted, however, IGF-1 does not directly cause cancer, however, if a cancerous cell culture is already forming then IGF-1 can increase the rate of growth through many of the same pathways it increases muscle growth.
In your body IGF-1 is spliced into many different variants that have different anabolic properties. IGF-1Ea and MGF seem to make up the greatest and more important spliced variants of the IGF-1 that is spliced in response to the process of lactosis (lactic acid oxidation caused by the “burn” you feel when lifting weights), which causes muscle damage. The lactic acid is currently thought to be the culprit as well for other irregular spliced variants of IGF-1, such as des 1-3 IGF-1, which is said to be 10 times more potent than that of IGF-1Ea. The most common variant seen in bodybuilding is Long Chain R3 IGF-1 or LR3 IGF-1. This is due to the fact that LR3 IGF-1 cannot be bound to the IGF-1 Binding Protein 3 (IGF-1 BP3). IGF-1 and IGF-1 BP3 levels are released based off circulating levels of each. As concentrations of IGF-1 in the body rise so do IGF-1 BP3 and as IGF-1 concentrations fall so do IGF-BP3 levels. Recent scientific evidence points out that the reason for IGF-1 BP3 levels rising due to increased levels of IGF-1 isn’t to inhibit too much hyperplasia or muscle growth (or basically to adhere to your genetic code) but instead to increase the half-life of circulating IGF-1. Unbound IGF-1 has a half life of around 20 minutes, where as when it’s bound to IGF-1 BP3 the half life is extended to around ~24 hours. This is why there is so much excitement surrounding LR3 IGF-1 and now MGF.
Although the exact pathways for muscle growth through the IGF-1 axis aren’t directly known or fully understood, a basic understanding has been established (see flow chart below) and common mechanisms are currently being discovered. It is thought that following muscle damage, circulating levels of IGF-1 are spliced towards MGF, which in turn signal muscle damage and begin to signal for increased nuclei/satellite cell production needed for mitosis and repair of the muscle. As seen in the graph below MGF levels are at their peak 2-4 days following muscle activity and begin to decline rapidly afterwards. IGF-1 levels begin to rise at the same time MGF levels begin to fall, around day 4, and it is though that IGF-1 completes the repairs by drastically increasing protein synthesis, increasing insulin sensitivity, and increasing muscle hyperplasia (the actually increase in the amount of muscle cells, not just the enlargement of muscle cells known as hypertrophy). Although many have stated that hyperplasia is impossible without exogenous use of IGF-1, this is a somewhat false statement; a better statement would be that IGF-1 induced hyperplasia occurs at a VERY slow rate naturally since at any given time less than 1% of all IGF-1 circulating in the blood is unbound from IGF-1 BP3. One must also know that despite IGF-1’s effects on muscle hyperplasia and the increased rate at which it occurs when using exogenous LR3 IGF-1, the overall results that are seen can often be seen at their greatest a decent amount of time post cycle. This occurs due to the fact that newly made muscle fibers are not matured instantly during the process of hyperplasia. Instead, these cells must go through the process of hypertrophy (increase in muscle fiber size) before they mature and become enlarged, another exciting reason to use a combination of MGF and LR3 IGF-1. This is the process of body recomposition that people talk so much about on the boards. You can technically work around your genetic limit and move past it.
Now that all of this basic knowledge of IGF-1 and MGF has been seen we can attempt to set up cycles based off of it. Actual dosing protocols for these growth factors (not including hGH) is quite difficult because unlike hormones such as T3 that can be tested for and, therefore, dosed according to circulating levels, it is almost impossible to detect how much MGF is released following muscle loading or how much of a spliced variant such as LR3 IGF-1 needs to be dosed to prevent antibody production or down regulation of receptors since LR3 IGF-1 doesn’t occur naturally in the body (except under freak splicing caused by lactic acid, which is a rare occurrence). This leads us into human testing based off abstract results by brave guinea pigs looking for that extra edge. Although great results have been seen dosing LR3 IGF-1 at 60-120mcg daily following intense exercise, results begin to taper off after around 4 weeks and down regulation of IGF-1 receptors and IGF-1 antibody production is currently thought to be the culprit. This leads one to believe that following a lower dosage scheme for a longer amount of time would be the way to go. It seems that not many people are willing to attempt a cycle consisting of 10-20mcg daily of LR3 IGF-1 due to the cost of LR3 IGF-1 being anywhere from $115-$200 depending on the source and many feel that a lower dosage would be a waste since “instant” results are not seen. Since hGH has been said to contribute most of its effects thanks to increased IGF-1 production, the level of IGF-1 produced by administrating exogenous hGH has to be extremely small compared to the amounts currently being injected, which is probably why exogenous hGH results last indefinitely, as seen by many people who use it year round. This would be one reason for lower dosage of IGF-1 to be used. An alternative camp says shorter cycles of higher dosages are more important since they want to rapidly increase the rate of muscle hypertrophy/hyperplasia before side effects and blunting effects are seen.
MGF dosages have also been widely debated. Although dosages are currently ranging from 20-100+ mcg injected bilaterally following intense exercises, you have to once again think to yourself how much MGF this is compared to the amount your body is naturally producing. If only less than 1% of IGF-1 is circulating through your blood unbound and MGF is produced from splicing IGF-1 into MGF than the amount relative to the 100mcg that people are currently administering is an extremely massive quantity. However, before you consider this a waste to inject this amount of exogenous MGF, it might be a good idea to use these concentrations after all, since the muscle could ultimately be extremely over trained, hitting much more of the muscle and causing greater damage to more muscle fibers and still be able to recover in time for the next workout due increased nuclei/satellite cell production. Add LR3 IGF-1 to the mix and you have a potent combination of recover and repair that your body uses itself after intense exercise. Since the cost of MGF is currently ~$100 per mg and the effects, unlike LR3 IGF-1, are localized, one should limit its use to 1 or maybe 2 lagging body parts per cycle to get the max effect. After review of all the evidence and scientific data it would seem logical to set up a dosage scheme such as the following although this has not be experimentally verified yet and there could be potentially better ways of dosing and cycling.
MGF + LR3 IGF-1 Dosage Scheme (following intense loading of lagging muscle group)
Pre Workout- 20-50mcg total MGF
Post Workout- 20-50mcg x 2 MGF (left and right sides of lagging muscle) following workout
Morning- 20mcg LR3 IGF-1 and 20-50mcg x 2 in lagging muscle group
Late afternoon- 20mcg LR3 IGF-1
Day 3 and 4
Morning- 30mcg LR3 IGF-1
Late Afternoon- 30mcg LR3 IGF-1
This is a great way to kick start a lagging muscle group with high dosages of potent growth factors. This dosage scheme follows the graph below, which is the body’s natural way of repairing muscle, just with much higher dosages. This dosage scheme also seems logical to prevent too much down regulation of receptors. Although there is no scientific data that backs up administering MGF pre workout, abstract results from various people indicate that better gains and quicker recovery times were observed, possibly due to the body ramping up satellite cell production around the same time as the workout has begun, so repairs occur faster since MGF takes time to ramp up increased nuclei/satellite cell production.
MGF Solo dosing:
There seem to be many schools of thought. Post workout is generally agreed on, but include a number of variations. The amount of Mechano Growth Factor administered differs greatly (from 20mcg – 100+mcg). While ultimately one dose doesn’t fit everyone’s needs, excessive amounts of MGF (without exogenous IGF-1 supplementation) have not yet proven to provide better results.
Below are some of the tried dosing protocols and their explanations. If possible, links have been provided to Logs of that particular dosing schedule and/or discussion on that particular method.
Post workout Only:
Description: Simply injecting Mechano-Growth Factor into the worked muscle after training. Your body expresses MGF in response to mechanical overload (micro trauma to muscle tissue). MGF is responsible for repair (by means of activating satellite cells to begin to donate (replicate) nuclei. These nuclei are then used to repair the damaged tissue. MGF is also responsible for muscle adaptation (hypertrophy). The reasoning behind this method is simple. Greater MGF expression leads to a greater response in muscle adaptation because the body thinks more damage has been caused then there actually is.
Post Workout +
(plus X days after)
Description: Similar to Post workout only, with MGF administration continued for a number of days afterwards. The reasoning here is supported by the bodies natural ability to express MGF longer then one day post workout. Increasing the amount of MGF in the trained muscle beyond the initial post workout injection should elicit a greater response for a longer time. It is important to note that at this time it is not known how long MGF (the Peptide) survives or remains active once injected. The length of time one would administer MGF post workout depends on many things unique to the user (recovery time, usage costs, diet…)
(x hours pre w/o, immediately after workout and following morning)
Description: This theory differs in regards to the above mentioned. MGF is administered hours BEFORE working the muscle. A post workout injection is also administered, and one the following morning (or about 12 hours after the post workout injection). The amount of MGF is not increased, rather user would split the dose used, using half a number of hours before exercise of the muscle, and the other half is to be used post workout. The 3rd dose would be a normal “full” dose 12 hours later. Thus method uses the same amount of peptide as the Post workout + protocol does (assuming MGF is administered the day after training and then ceased).
The reasoning behind this protocol is believed to be that the pre-workout injection a few hours before training activates the satellite cells to donate their nuclei. Since there is not yet muscle damage, the donated nuclei will increase in number. This increase before muscle trauma gives a “head start” in the repair process via having already pre-made, available cells the second damage occurs to the muscle, speeding recovery (and/or increased training ability).
As time progresses, and more research is done, this will be UPDATED. You can check it out here http://www.thefilehut.com/userfiles/...F-1Compile.doc
Last edited by AnabolicAndre; 04-01-2006 at 05:30 PM.
03-29-2006, 06:14 PM #2
Itssss long but, very informative.
Hope you guys can put it to good use.
03-29-2006, 06:45 PM #3
04-01-2006, 10:40 AM #4Banned
- Join Date
- Mar 2006
Yes, I wrote this, but AnabolicAndre, I specifically stated that if you are going to be posting this on other forums to please do so by either linking to the *************.com website thread of it or by posting this link http://www.thefilehut.com/userfiles/...F-1Compile.doc .
This isn't to be a dick or to swing traffic but this thing gets updated every day. In fact that current one you have posted is very out of date as far as information is concerned. I spoke with Dr. Goldspink on the subject and some of his older studies that I based some of my research off of has been corrected, please fix the above thread so we don't have a million copies of this thing floating around and we have updated information for everyone.
04-01-2006, 12:18 PM #5
Nice way to stay on top of it
04-01-2006, 05:26 PM #6Banned
- Join Date
- Aug 2005
The fact is it is made by that crap company I B E,the company that makes oral IGF....can you trust them?
04-01-2006, 05:31 PM #7Originally Posted by goose4
Its not actually made by them, but they have been lucky enough to get the peptide for people who want to use it.
04-01-2006, 05:57 PM #8Originally Posted by goose4
04-01-2006, 06:00 PM #9Originally Posted by LakeMountD
04-01-2006, 06:10 PM #10Banned
Originally Posted by JohnnyB
- Join Date
- Mar 2006
All studies have the exact people who did the studies as well as citations.
*** can definitely be trusted as well. They will have injected LR3 IGF-1 soon by the way so that will compliment well to the MGF they currently have. Read through my paper (which you can find from that link I supplied a couple posts up) and it will explain why.
04-02-2006, 11:25 PM #11
thanksOriginally Posted by LakeMountD
04-03-2006, 05:45 PM #12Originally Posted by LakeMountD
04-04-2006, 09:48 AM #13Originally Posted by JohnnyB
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