MGF (Mechano Growth Factor, lGF-IEc, MGF Goldspink, PEG MGF)

Description:

Mechano Growth Factor (MGF) is an anabolic hormone from the Growth Hormone family of substances. It was discovered in 1996, when it was found to be a natural ‘splice variant’ of IGF-I (Insulinlike Growth Factor). That is, it is an alternate sequence of IGF-I that is produced locally within the muscles when they are stretched or damaged, as with resistance training.1 2 This new form of IGF-I seems to trigger some of the early changes within the cells that support repair and growth, making it of great interest in both medical research and sports doping.3 The technical label for this variant of IGF-I is human IGF-IEc. However, it is often called MGF because it appears to play a key role in translating mechanical activity into anabolic signaling (growth).

The physiological activity of MGF (human IGF-IEC) has not been fully characterized. What we do know is that this hormone acts in a local or paracrine fashion to support the repair of skeletal and cardiac muscles after damage. Protein synthesis is upregulated in response to MGF. Perhaps more interestingly, it stimulates the satellite cell cycle.4 MGF has been specifically shown to activate quiescent satellite cells. These then proliferate, which expands the pool of precursor cells that are available to use for repair and growth. The satellite cell cycle is a core part of ongoing hypertrophy. It ultimately contributes nuclei to expanding muscle cells, which allows them to continue managing their growing volume efficiently. Hypertrophy simply halts without it

It is also interesting to note that anabolic steroid administration has been shown to substantially increase the post-exercise expression of mechano growth factor.5 This suggests there is some direct androgen regulation of MGF splicing in skeletal muscle. More research is needed on serum androgen differences in the MGF response, of course. But these findings do underline just how robust steroids are as anabolic drugs, and how they influence muscle growth via diverse, not isolated, pathways. Potentially further, that some of their effects can be replicated with other substances. More work will be needed to fully elucidate the potential synergies between anabolic steroids and drugs from the growth hormone family.

Complicating our discussion about MGF as a drug, however, is the fact that several different variants of this protein have been used during scientific studies. Though seemingly similar, some pharmacodynamic differences have been observed.6

Likewise, the research on MGF can easily become confused if one is not aware of the subtle differences between these proteins. The three most popular forms of MGF are reviewed below. However, it is important to point out that this list is not inclusive. Other variants have been used in scientific research, as well in the realm of sports doping.7 8 Until such time as this protein is developed into one standardized drug, confusion among consumers is likely to persist.

Native MGF: This is natural human MGF (IGF-IEC), Native MGF contains a sequence of 110 amino acids. It is formed when the body produces an alternate splicing of IGF-1 (normally 70 amino acids). Full length MGF is a complex and expensive protein to manufacture. It is available for research purposes, though is rarely found outside of the lab

Truncated Native MGF: This is a shortened form of native MGF, consisting of its C-terminal sequence of 24 amino acids. This is considered to be the hypertrophic ‘active domain’ of the MGF protein, retaining all of its anabolic properties. As a much shorter chain, this truncated MGF is easier to manufacture than full length MGF, and should be much more stable. This is the MGF protein most commonly used in the fitness community. For the most part, when we are talking about MGF as a drug, we’re talking about this protein.

Goldspink MGF: This is a modified form of Truncated Native MGF. It is named after the scientist that discovered MGF, and also developed this more stable analog. In this protein, two arginine residues are replaced with D-arginine, and a third at position 23 is replaced with histidine. This compound is sometimes also called ‘R23H MGF’ It is available and used in the fitness community, but less commonly than Truncated Native MGF. It should be significantly more effective, however. This is generally the preferred form of MGF.

As with many other peptides, MGF proteins are also available in both regular and ‘pegylated’ form. Regular is just straight MGF protein. The substance is still effective when administered in this form, though is extremely fast acting. Regular MGF requires daily injections in order to be therapeutically viable. Pegylation is much slower acting. This involves attaching a polyethylene glycol (PEG) molecule to the protein. Pegylation protects MGF from enzymatic degradation, greatly extending its half-life. This type of MGF protein requires only 2-3 injections per week, which seems much more viable for most users.

Pegylated mechano growth factor or ‘PEG MGF’ is the most common type of MGF available today.

Research on mechano growth factor is still in its early stages. The data so far is highly encouraging, but also limited. What we know of the anabolic effect of MGF is largely gleaned from anecdotal reports. The feedback has been mixed. It is also likely to vary depending on what MGF protein is used, the manner in which it is used, and of course, its purity. At this time, it is very difficult to draw concrete conclusions. Detailed human studies into the different MGF proteins, as well as their optimal dosing and usage protocols, are needed.

History:

Mechano Growth Factor was first described in 1996 by Goldspink et al.9 Shortly after its isolation, a series of MGF variants were synthesized and studied. Many MGF proteins are based on a shortened form of the native hormone, specifically its C-terminal sequence of 24 amino acids. This has been shown to be the active core moiety of MGF; the only essential part for imparting anabolic effects. Though animal studies on this family of compounds has returned some promising early data, MGF does not appear poised to enter clinical trials and pharmaceutical development at this time. However, research on this hormone does continue. MGF is on WADA’s list of prohibited substances, and methods for its detection (at least some of the variants) are available.10

How Supplied:

This drug is not available as a pharmaceutical product. Standard dosage information is unavailable

MGF can be purchased as a research compound only. It is typically supplied in multi-dose vials containing 2 mg or 5 mg of dry lyophilized powder. This must be reconstituted with saline or bacteriostatic water before use. All unused portions of this drug should be kept under refrigeration.

Structural Characteristics:

Truncated Native MGF is a polypeptide containing 24 amino acids in the following sequence: PEG-Tyr-Gln-ProPro-Ser-Thr-Asn-LysAsn-Thr-Lys-Ser-Gln-Arg-Arg-Lys-GlySer-Thr-Phe-Glu-Glu-Arg-LysNH2.

Goldspink MGF is a polypeptide containing 24 amino acids in the following sequence: PEG-Tyr-Gln-Pro-Pro-SerThr-Asn-Lys-Asn-ThrLys-Ser-Gln-(d)Arg-(d)Arg-Lys-GlySer-Thr-Phe-Glu-Glu-His-LysNH2 (substitutions in bold).

Warnings:

MGF is an unapproved new drug. A thorough understanding of its safety and propensity for side effects

in humans is lacking at this time.

Side Effects (General):

According to anecdotal reports, common side effects to MGF include joint pain (arthralgia), carpal tunnel syndrome, and numbness or tingling in the extremities. Some have also reported flushing, sleepiness, and lethargy. Injection site reactions are also possible (See below). Otherwise, the safety and adverse reaction profile of this drug are not fully characterized at this time.

Side Effects (Injection site):

The subcutaneous administration of this drug may cause redness, itching, pain, and/or lumps at the site of injection.

Administration:

This drug is not available as a pharmaceutical product. Standard dosage information is unavailable.

This drug is not available as a pharmaceutical product. Standard dosage information is unavailable

Regular MGF: When used for physique- or performanceenhancing purposes, Regular MGF is usually administered at a dosage of 50-200 mcg. This is generally given via IM injection(s) once daily, immediately following exercise in the muscle(s) trained. Regular MGF is typically taken on training days only, but as many as 5-6 days per week.

The daily dosage of Regular MGF may be further divided across multiple injections into the muscles just trained. This is in an effort to support enhanced site-specific muscle growth. For example, a 200mcg dosage may be split into 4 injections of 50 mcg each, administering 2 in each bicep. The efficacy of this practice is unclear, but supported anecdotally

PEG MGF: When used for physique-enhancing purposes, PEG-MGF is usually administered at a dosage of 150-300 mcg. This is typically given by IM or subcutaneous injection, 2-3 times per week. Some do follow a similar practice to Regular MGF, dividing the dosage into multiple IM injections within each of the muscles just trained. However, many are less inclined to do so given the slower activity of this drug, and its more comfortable injection schedule. Again, best practices have yet to be established.

Cycles of MGF usually last 2-3 months, though longer programs are not uncommon.

Combination Therapy:

MGF has been shown to support the early proliferative stage of the satellite cell cycle. It is often combined with GH or IGF-1, which should provide more robust stimulation of the latter stages of the satellite cell cycle, improving the overall anabolic response to therapy.

Availability:

MGF is not available as a prescription drug product. It is sold exclusively as a ‘research compound’ or gray market supplement. Note that the quality of gray market products can be difficult to assure. In our experience, MGF can be an especially risky product to purchase from unknown sources. It is expensive and difficult to source, which increases (greatly) the likelihood it will be substituted with something else. Care should be taken to locate a reliable supplier, if this substance is desired.

1 Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. Mckoy, G., Ashley, W., Mander, J., Yang, S.Y., Williams, N., Russell, B., and Goldspink, G. J. Physiol.516:583-592. 1999

2 Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch.J. Muscle. Res. Cell. Motil. 17:487-495.Yang, S., Alnaqeeb, M., Simpson, H., and Goldspink, G. 1996.

3 Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping FREE G Goldspink

4 Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. Yang, S.Y., Goldspink, G. FEBS Lett. 522:156-160.2002

5 The Effect of Anabolic Steroid Administration on Passive StretchingInduced Expression of Mechano-Growth Factor in Skeletal Muscle. Satoshi Ikeda et al. The Scientific World Journal Volume 2013, Article ID 313605

6 Mechano-Growth Factor Reduces Loss of Cardiac Function in Acute Myocardial Infarction. Violaine Carpenter et al. Heart, Lung and Circulation 2008;17:33-39

7 Characterization and identification of a C-terminal amidated mechano growth factor (MGF) analogue in black market products. Esposito S, Deventer K, Van Eenoo P. Rapid Commun Mass Spectrom. 2012 Mar 30;26(6):686-92.

8 Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls. Mario Thevis, et al. Growth Hormone & IGF Research 24 (2014) 276-280

9 Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch. Yang S, Alnaqeeb M, Simpson H, Goldspink G.J Muscle Res Cell Motil. 1996 Aug;17(4):487-95.

10 Expanded test method for peptides >2 kDa employing immunoaffinity purification and LC-HRMS/MS. Thomas A, Walpurgis K, Tretzel L, Brinkkötter P, Fichant E, Delahaut P, Schänzer W, Thevis M. Drug Test Anal. 2015 Nov-Dec;7(1112):990-8