Picture this: you’ve been strictly following your workout routine, lifting heavier weights, and meticulously tracking your calories.
Yet your muscle gains are nonexistent and instead, you find yourself struggling with unwanted fat gain.
This is a common frustration faced by millions of frustrated bodybuilders, biohackers, athletes, and everyday gym-goers seeking a better body.
This is where peptides like PEG-MGF may help turn things around.
PEG MGF not only promotes skeletal muscle tissue growth and strength gains, but also boasts regenerative properties that help heal injuries or wounds from intense weightlifting.
Therefore, it’s no surprise that PEG-MGF has become a favorite among fitness enthusiasts.
Whether you’re an experienced athlete or just starting out, this article will discuss what PEG MGF is and how it can boost your muscle-building journey
What is Pegylated Mechano Growth Factor (PEG-MGF)?
Pegylated Mechano Growth Factor (PEG-MGF) is a synthetic version of the mechano-growth factor (MGF) peptide enhanced through a chemical reaction called PEGylation.
PEGylation attaches polyethylene glycol (PEG) to the molecule, extending the peptide’s half-life so that it won’t be as easily eliminated by the kidneys.
As a split variant of insulin-like growth factor-1 (IGF-1), PEG-MGF can be found in the bones, muscles, brain, tendons, and heart tissue after an increased load of stress (ex. an intense workout).
It promotes muscle growth and accelerates recovery from muscle damage, which is why it is perceived as one of the go-to options for building skeletal muscle mass by bodybuilders and athletes.
How Does PEG-MGF Work?
PEG-MGF helps stimulate muscle stem cell fusion, myoblast division, and maturation, thereby promoting muscle growth.
It works by boosting muscle stem count and promoting the development of new muscle cells.
PEG-MGF also regulates inflammation of the muscles and improves their regeneration by increasing the recruitment of neutrophils and macrophages at the site(s) of injury, resulting in faster recovery and muscle growth.
Additionally, it boosts the number of neural progenitor cells, promoting the formation of new neurons via neurogenesis
Finally, PEG-MGF protects the function of cardiac muscle via the inhibition of apoptosis and enhancement of cardiac stem cell proliferation.
PEG-MGF vs MGF: What’s the Difference?
MGF is a variant of IGF-1 but has a different sequence from the IGF-1 produced by the liver.
When IGF-I is spliced to make MGF, this promotes muscular hypertrophy and begins the bodily process of muscle damage repair.
However, MGF has a short half-life of 5-7 minutes.
Researchers were able to solve this dilemma by pegylating MGF, increasing its half-life of 48- 72 hours.
This is what allowed the peptide to become a viable therapeutic candidate for muscle growth.
But what does the science have to say about this modification?
Research and Benefits of PEG MGF Peptide
Muscle Repair and Growth
As previously stated, PEG-MGF is a muscle growth peptide that promotes muscle recovery.
It accelerates the healing process of muscle tissue while improving overall muscle strength and endurance, two important goals for any bodybuilder seeking to gain lean mass.
A study in the Journal of Mechanisms of Ageing and Development showed that PEG-MGF improved muscle repair in patients with age-related sarcopenia:
“Loss of muscle mass and strength is a major problem during aging and the expression of Mechano Growth Factor (MGF), a member of the IGF-1 (insulin-like Growth Factor 1) super family, has been shown to be both exercise and age dependent.
MGF, also called IGF-1Ec, has a unique E domain with a 49bp insert in humans (52bp in rodents; IGF-1Eb), which results in a reading frame shift during the IGF-1 gene splicing to produce a distinct mature isoform.
We have studied the effects of the MGF-24aa-E peptide on proliferation and differentiation of primary human muscle cell cultures isolated from healthy subjects of different ages.
We found that MGF-E peptide significantly increases the proliferative life span and delays senescence of satellite cells isolated from neonatal and young adult but not from old adult muscle, hypertrophy associated with a significant decrease in the percentage of reserve cells was observed in all cultures.
It is concluded that the MGF-24aa-E peptide alone has a marked ability to enhance satellite cell activation, proliferation and fusion for muscle repair and maintenance and could provide a new strategy to combat age related sarcopenia without the oncogenic side effects observed for IGF1.”
In another study published in Bioscience Reports, PEG-MGF slowed the progress of muscle wasting in rats with mechanical-induced disc degeneration.
Sometimes, mechanical overload can lead to disc degeneration through the induction of cell apoptosis.
Mechano growth factor (MGF) has been shown to inhibit this process, therefore preventing the apoptosis of chondrocytes (i.e. cartilage cells) caused by mechanical overload.
“Rat NP cells were cultured and subjected to mechanical overload for 7 days.
The control NP cells did not experience mechanical load. The exogenous MGF peptide was added into the culture medium to investigate its protective effects. NP cell apoptosis ratio, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3, protein expression of cleaved caspase-3, cleaved PARP, Bax and Bcl-2 were analyzed to evaluate NP cell apoptosis. In addition, activity of the p38 MAPK pathway was also detected.
Compared with the control NP cells, mechanical overload significantly increased NP cell apoptosis and caspase-3 activity, up-regulated gene/protein expression of pro-apoptosis molecules (i.e. Bax, caspase-3, cleaved caspase-3 and cleaved PARP) whereas down-regulated gene/protein expression of anti-apoptosis molecule (i.e. Bcl-2).
However, exogenous MGF partly reversed these effects of mechanical overload on NP cell apoptosis.
Further results showed that activity of the p38 MAPK pathway of NP cells cultured under mechanical overload was decreased by addition of MGF peptide.
In conclusion, MGF is able to attenuate mechanical overload-induced NP cell apoptosis, and the p38 MAPK signaling pathway may be involved in this process.”
And in a in the British Journal of Sports Medicine, mice given MGF saw a 25% boost in their muscle fiber size within three weeks:
“One of the methods we used to establish the biological action of MGF was to engineer a gene into which its cDNA was inserted into a vector.
To our surprise a single intramuscular injection into a mouse muscle resulted in a 25% increase in mean muscle fibre cross section area within three weeks.
Similar experiments have been carried out using the systemic or liver type of IGF-I in an adenoviral vector under the control of a muscle regulatory sequence.
However, this took four months to produce a 15% increase and is probably due to the anabolic effect of IGF-I, which is common to all the splice variants.
The use of the DNA of IGF-I and particularly MGF is therefore a prime candidate for gene doping for enhancement of athletic performance.”
Bone Regeneration
PEG-MGF has also been shown to accelerate bone regeneration, making it useful for people recovering from fractures or other bone injuries.
It stimulates the proliferation and differentiation of bone cells, leading to faster and more effective healing of bone tissue.
This makes it one of the best peptides for athletes and bodybuilders looking to avoid injury at all costs.
In fact, the PEG-MGF peptide regulates bone-performing cells in rabbits, which aids in faster bone healing as evidenced in a Journal of International Orthopaedics paper:
“To assess the potential efficacy of mechano growth factor (MGF) for bone injury, we firstly investigated the effects of growth factors, including MGF, its E peptide (a short 24-amino acid C-terminal peptide, MGF-Ct24E), and insulin-like growth factor 1(IGF-1) on MC3T3-E1 osteoblast-like cell proliferation.
MGF-Ct24E had the highest pro-proliferation activity among three growth factors, which was 1.4 times greater than that of IGF-1.
Moreover, MGF-Ct24E promoted cell proliferation by inducing cell cycle arrest in the S and G(2)/M phase of the cell cycle, but also mainly by the activation of the MAPK-Erk1/2 pathway.
In vivo, a 5-mm segmental bone defect in the radius of 27 rabbits was treated with MGF-Ct24E by two doses (28.5 and 57 μg /kg body weight) vs. non-growth factor injection for five consecutive days postoperatively.
The cumulative rate of radiographically healed defects and histological scores of bone defect-healing revealed a statistical difference between high-dose treatment and non treatment (p < 0.01), which showed the treatment promoted defect healing.
This report is the first to demonstrate that MGF-Ct24E possesses positive effects on osteoblast proliferation and bone-defect healing, suggesting a new strategy in fracture healing.”
In a separate study involving mice, the administration of MGF was found to facilitate the migration of chondrocytes from bone tissue to the cartilage, helping in the repair and regeneration of broken cartilage:
“Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading.
Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair.
However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli.
Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload.
Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration.
Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation.
Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli.
MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis.
Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling.”
Cardiovascular Protection
PEG-MGF can help protect against cardiovascular disease by improving vascular function and reducing inflammation.
Additionally, PEG-MGF helps enhance the repair of damaged blood vessels, further contributing to its potential cardiovascular benefits.
This has been shown in Heart, Lung, and Circulation, where PEG-MGF was proven to protect sheep hearts from ischemia and boost their heart function after a heart attack:
“Infarcts were induced by injection of microspheres. In experiment 1, sheep were treated with vehicle, 200 nM each of mature IGF-I, MGF E domain, or full-length MGF.
In experiment 2, sheep were treated with vehicle or 200 nM of MGF E domain alone. Cardiac function was assessed using echocardiography and sheep were killed eight days post-MI.
Evans Blue dye was injected before death to stain the compromised myocardium. Immunohistochemistry was used to assess the abundance of pAkt(T308) and cleaved caspase 3.
In experiment 1, cardiac function improved in sheep treated with the MGF E domain, while in experiment 2, MGF E domain preserved cardiac function and there was 35% less compromised cardiac muscle than controls.
Furthermore, immunostaining of cleaved caspase 3 was absent in MGF E domain-treated hearts, suggesting that MGF E domain reduced infarct expansion.”
In another study published in the Journal of Biomedical Microdevices, PEG-MGF was shown to prevent programmed cell death of heart muscles, further minimizing the risk of heart disease:
“Local release of drugs may have many advantages for tissue repair but also presents major challenges. Bioengineering approaches allow microstructures to be fabricated that contain bioactive peptides for sustained local delivery.
Heart tissue damage is associated with local increases in mechano growth factor (MGF), a member of the IGF-1 family. The E domain of MGF peptide is anti-apoptotic and a stem cell homing factor.
The objectives of this study were to fabricate a microrod delivery device of poly (ethylene glycol) dimethacrylate (PEGDMA) hydrogel loaded with MGF peptide and to determine the elution profile and bioactivity of MGF.
The injectable microrods are 30 kPa stiffness and 15 μm widths by 100 μm lengths, chosen to match heart stiffness and myocyte size. Successful encapsulation of native MGF peptide within microrods was achieved with delivery of MGF for 2 weeks, as measured by HPLC.
Migration of human mesenchymal stem cells (hMSCs) increased with MGF microrod treatment (1.72 ± 0.23, p < 0.05).
Inhibition of the apoptotic pathway in neonatal rat ventricular myocytes was induced by 8 h of hypoxia (1 % O2). Protection from apoptosis by MGF microrod treatment was shown by the TUNEL assay and increased Bcl-2 expression (2 ± 0.19, p < 0.05).
Microrods without MGF regulated the cytoskeleton, adhesion, and proliferation of hMSCs, and MGF had no effect on these properties.
Therefore, the combination microdevice provided both the mechanical cues and 2-week MGF bioactivity to reduce apoptosis and recruit stem cells, suggesting potential use of MGF microrods for cardiac regeneration therapy in vivo.”
Neuroprotective Effects
PEG-MGF has also demonstrated neuroprotective properties that protect and support nerve cell health.
It may help mitigate neurological damage and promote neural regeneration.
In fact, Mayo Clinic researchers discovered that MGF can prevent age-related neuron degeneration (such as neuronal attrition and brain dysfunction) in mice:
“In this study, transgenic mice were bred so as to constitutively overexpress MGF in the hippocampus and the subventricular zone of the brain – regions associated with neural development and differentiation (neurogenesis).
Histological analysis confirmed that these transgenic specimens displayed an abnormally high concentration of BrdU, a synthetic marker for detecting proliferating cells in live tissues. This indicates increased cell proliferation and growth in the specific regions of the brain.
Another group of double transgenic mice was then bred to display conditional MGF expression when triggered by the presence of an activating agent added to their drinking water.
Using this new population, researchers were able to study the long-term effects of enhanced neural MGF production when triggered at 1, 3 or 12 months old. Behavioral analysis and further histological assays were then conducted at 24 months.
With significantly higher levels of BrdU+ proliferative cells in the brain, the mice with MGF overexpression also displayed an enhanced resistance to age-related neural degeneration, as evidenced by their improved olfactory behavior.
Mice with enhanced levels of neurogenesis displayed greater speed and higher success in cognitive tests.
An interesting finding was that the efficacy of MGF was highly age-dependent.
The earlier that MGF overexpression was induced, the more dramatic the eventual proliferation of BrdU+ cells, and subsequent neurological improvement throughout adulthood.
If MGF production was not stimulated by the time the mice were 12 months old, they displayed no significant histological or behavioral differences to the control group.”
Additionally, findings in Journal of Neuroscience Research suggest that PEG-MGF can prevent programmed brain cell death due to oxidative stress, thus lowering the risk of stroke:
“Recently, a variant of insulin-like growth factor-1, mechano-growth factor (MGF), has been discovered whose 24-amino-acid carboxy end is protective in models of stroke, nerve injury, and amyotrophic lateral sclerosis, suggesting broad-spectrum neuroprotective properties.
Moreover, we recently demonstrated in vitro and in vivo that a modified protease-resistant 24-amino-acid MGF derivative (MGF24) protects dopaminergic neurons from oxidative stress-induced apoptosis via induction of the stress response protein heme oxygenase-1.
However, the underlying mechanism by which MGF24 up-regulates heme oxygenase-1 expression is unknown.
In this study, we demonstrate that MGF24-induced heme oxygenase-1 up-regulation is dependent on activation of protein kinase Cϵ and NF-E2-related factor-2 (Nrf2).
MGF24 induces nuclear translocation of Nrf2, and siRNA knockdown of Nrf2 or of heme oxygenase-1 prevents MGF24-induced heme oxygenase-1 up-regulation and neuroprotection of SH-SY5Y cells against 6-hydroxydopamine-induced cell death.
Pharmacological inhibition of ERK, p38 MAPK, PI3K/Akt, or PKC signaling revealed that only PKC inhibition by GF109203X prevents MGF24’s ability to protect against 6-hydroxydopamine-induced cell death.
GF109203X also prevented MGF24-induced Nrf2 nuclear translocation and heme oxygenase-1 up-regulation.
siRNA knockdown of protein kinase Cϵ blocks MGF24-induced Nfr2 nuclear translocation, heme oxygenase-1 expression, and neuroprotection.
Taken together, these results demonstrate that PKC activity is needed for MGF24’s activation of Nrf2, which in turn increases heme oxygenase-1 expression, a critical event in mediating MGF24’s neuroprotection against 6-hydroxydopamine-induced apoptosis.”
This might make PEG-MGF worthy of being added to the list of effective nootropic peptides!
PEG-MGF Dosage
To use PEG-MGF, a starting protocol could involve injecting 150 mcg of PEG-MGF per day — subcutaneously or intramuscularly — in the area you want to target for localized delivery.
The injections can be done once a day, 2-3 times a week over a period of 8-10 weeks.
Should You Use PEG MGF for Bodybuilding?
PEG-MGF’s main properties in the context of bodybuilding are straightforward:
- Aids muscle repair and growth
- Stimulates muscular hypertrophy via enlargement of muscle fibers
- Promotes proliferation of satellite cells for muscle tissue regeneration
However, PEG-MGF also aids in fat loss by improving the body’s ability to utilize stored fat as an energy source.
This dual mode of action makes PEG-MGF a powerful addition to any bodybuilder’s muscle-building toolbox.
Combined with its ability to significantly speed up the rate of healing from various injuries, it can also help athletes recover faster and stay in the gym without extended breaks.
Potential PEG-MGF Side Effects
PEG-MGF side effects are very uncommon.
As long as you use the minimum effective dose and follow the protocol mentioned earlier, the chances of experiencing side effects are little to none.
You do not want to misuse the peptide as doing so may lead to the following:
- Blood pressure drop
- Hypoglycemia (low blood sugar levels)
- Irregular heart rate
- Swelling of the extremities
Speak to a medical professional if you are unsure whether PEG-MGF is right for you.
Jay’s Closing Thoughts
I first wrote about PEG-MGF years ago in an email and then repurposed it in my article about the 5 best peptides for muscle growth.
I also followed up two years later with my best peptide stacks for muscle growth.
All of this is to say I currently do not endorse the use of PEG-MGF for anybody seeking SERIOUS skeletal muscle mass gains.
In both articles, I outlined (as of now) three ways a natural or synthetic agent can meaningfully promote the development of lean muscle tissue:
- Increase HGH production/secretion
- Increase insulin-like growth factor 1 (IGF-1)
- Inhibit myostatin production
I also clarified that any peptide responsible for the direct or indirect growth of muscle tissue will not work unless the following three elements are dialed in:
- Consistently eating at a caloric surplus
- Following the principles of progressive overload and positive muscular failure
- Adequately resting and recovering through “off” days and optimal sleep hygiene
As of right now, there are no therapeutic peptides (USED IN ISOLATION) that reliably help any natural or enhanced athlete maximize muscle gain in a meaningful manner.
This is why you won’t see them in the muscle-building toolbox of any successful bodybuilder competing at the highest levels.
What you’ll find instead is the following: Therapeutic testosterone, pharma-grade HGH, anabolic steroids, insulin and maybe pure IGF-1 if they can find it.
Does this mean there will never be a peptide fully endorsed by Jay Campbell for taking someone from being tiny to being a titan?
Of course not… the future of therapeutic peptides is still vast with untapped potential.
In fact, many pharmaceutical companies are racing to build a safe yet effective agent that will eliminate the “so-called” muscle loss resulting from using GLP-1 receptor agonists. (This happens ONLY with GLP-1 users who are poorly informed on how to use these agents-my newest course prevents muscle loss when using GLP-1 peptides)
For instance: Bimagrumab, a human monoclonal antibody, shows promise in “rapidly increasing skeletal muscle mass in various muscle-wasting conditions, including disuse atrophy and sarcopenia” (Source).
The simultaneous loss of fat mass and preservation (if not slight gain) of lean mass, even in the presence of a caloric deficit, has been observed in both mice studies and human clinical trials.
Versantis, the biotech company responsible for manufacturing this compound, was recently acquired by Eli Lilly (the manufacturer of Tirzepatide) for a cool $1.9 billion.
So don’t count out peptides just yet!
But until you get the green lights from me, just stick with what is tried and true.
Key Takeaways: Is PEG-MGF Legit?
While PEG-MGF has not been approved by the FDA for medical use, it remains a popular choice among fitness enthusiasts and bodybuilders due to its muscle-building properties.
When used correctly, PEG MGF may enhance muscle growth, improve recovery time, and promote fat loss, helping you achieve your bodybuilding goals more effectively.
However, make sure you’re sourcing PEG-MGF from a reputable company to ensure you get the results you desire safely.
I trust Limitless Life Nootropics because they are the biohacking industry’s only reliable vendor for 3rd-party tested research products.
They have the best formulations of therapeutic peptides available, and no other vendor comes close to offering them at ultra-high levels of purity for reasonable prices.
But keep in mind PEG-MGF is not stocked by Limitless… for potential muscle gain, you’ll want to seek out peptides such as 5-Amino 1MQ, Ipamorelin and Tesamorelin.
Use code JAY15 to get 15% off your order
But before you start injecting these peptides into your body recklessly, make sure you first read the Top 10 Mistakes People Make When Starting Therapeutic Peptides FREE PDF!
Seriously, this short e-book will save you a lot of wasted money and poorly spent time (not to mention preventing you from potential self-inflicted missteps).
And the emails I’ll send you after downloading the book contain an EXCLUSIVE 33% OFF code for my Peptides Demystified Course, so don’t miss out!
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