Side-by-side · Research reference

MGFvsPE 22-28

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED14/55 cited

BAnimal-StrongHUMAN-REVIEWED16/47 cited

MGF

IGF-1Ec Splice Variant · Muscle-Specific

IGF-1EcSplice variantArmakolas 2016

24-AASynthetic E-domain

Animal onlyHuman evidence

SQ · Research context only

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

01Mechanism of Action

Parameter

MGF

PE 22-28

Primary target

Satellite cells (Pax7+) in skeletal muscleMoore 2018

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Pathway

Mechanical stress → IGF-1Ec mRNA upregulation → Local E-domain peptide release → Satellite cell activation

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

Downstream effect

Satellite cell proliferation, myoblast differentiation, muscle fiber repair

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

Feedback intact?

—

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Origin

Alternative splicing of IGF-1 gene (exons 4-6) produces IGF-1Ec precursor; E-domain cleaved post-translationallyArmakolas 2016 Vassilakos 2017

Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017 Mazella 2018

Antibody development

—

Not reported in animal studies

02Dosage Protocols

Parameter

MGF

PE 22-28

Synthetic peptide

24-amino-acid E-domain sequence

Corresponds to human IGF-1Ec exons 4-6 region.

—

Rodent cardiac model

200 μg/kg via peptide-eluting microstructures

Post-MI injection; improved ejection fraction by 8 weeks.

—

Acute delivery (mouse MI)

Single bolus within 12 hrs post-infarctionShioura 2014

Delayed decompensation; no human protocol established.

—

Human evidence

None — no published clinical trials

All dosing extrapolated from animal models.

—

Detection in doping

Full-length MGF detected via LC-MS in illicit productsThevis 2014

WADA-prohibited since 2005; no therapeutic indication.

—

Evidence basis

Animal models + in vitro only

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

Animal dose (antidepressant)

—

0.3–3 µg/kg IP

Effective in forced swim test, tail suspension test, CUMS models.

Animal dose (neuroprotection)

—

0.03 µg/kg IPPietri 2019

Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.

Frequency

—

Once daily

Sustained antidepressant effect over 7+ days.

Onset (animal)

—

Within hours (acute); full effect 4–7 days

Duration (animal)

—

7–28 days testedQi 2018 Pietri 2019

Comparison to fluoxetine

—

PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7

Chronic administration shows superior long-term efficacy.

Human equivalent (extrapolated)

—

Not established — no clinical trials

Allometric scaling from rodent data unavailable.

04Side Effects & Safety

Parameter

MGF

PE 22-28

Human safety data

None — no clinical trials published

—

Theoretical IGF-1 axis risk

Chronic IGF-1Ec overexpression linked to cancer progression (prostate, colorectal, breast)

—

Tumor promotion

IGF-1Ec overexpressed in osteosarcoma, colorectal polyps with dysplasia, endometrial cancer

—

Antibody development

Unknown — no longitudinal human exposure data

—

Local injection reaction

Presumed similar to other peptides (erythema, induration) — no direct evidence

—

Dysregulated expression with age

Older adults (70+ yrs) show blunted IGF-1Ec response post-exercise vs youngMoore 2018

—

Toxicity (animal)

—

No adverse effects reported at therapeutic doses

Cardiovascular (theoretical)

—

TREK-1 expressed in cardiac tissue; arrhythmia risk unclear

Weight change

—

Not reported in animal studies

Neurological

—

No seizures or behavioral abnormalities noted

Long-term safety

—

Unknown — longest animal study 28 days

Absolute Contraindications

MGF

·Active malignancy or history of IGF-1-sensitive cancers (prostate, colorectal, breast, osteosarcoma)
·No established therapeutic use — investigational only

PE 22-28

·Human use — no clinical safety data available

Relative Contraindications

MGF

·Family history of IGF-1-axis malignancies
·Use outside research setting

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

05Administration Protocol

Parameter

MGF

PE 22-28

1. No validated protocol

MGF (E-domain peptide) has no approved clinical protocol. All published data derive from animal models or in vitro experiments.

Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.

2. Synthetic peptide form

Commercially available MGF corresponds to the 24-amino-acid human E-domain (hEc). Rodent E-domain (Eb) is structurally distinct and not interchangeable.

Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017

3. Animal delivery models

Rodent studies used peptide-eluting polymeric microstructures (cardiac) or direct intramuscular injection. Routes and doses non-translatable to humans.Peña 2015 Shioura 2014

Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.

4. WADA prohibition

MGF peptides prohibited in sport since 2005. Detection via LC-MS established for full-length MGF products.Thevis 2014

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

5. Research context only

Any human use falls outside approved medical practice and regulatory frameworks. No safety or efficacy data exist.

—

06Stack Synergy

MGF

+ BPC-157

Multi-pathway

View BPC-157 →

MGF activates satellite cells for muscle fiber repair; BPC-157 promotes angiogenesis, collagen synthesis, and tendon healing via distinct pathways (VEGF, FAK, integrin signaling). Theoretical synergy in post-injury contexts combines myogenic (MGF) and stromal (BPC-157) repair mechanisms. Both lack human validation.

MGF: No established dose
BPC-157: 250–500 mcg SQ near injury site
Context: Animal models only
Primary benefit: Theoretical multi-tissue repair (muscle + tendon/ligament)

+ TB-500

Moderate

View TB-500 →

TB-500 (thymosin beta-4 fragment) enhances actin polymerization, cell migration, and angiogenesis—complementary to MGF satellite cell activation. Both upregulated post-injury; combined use presumed additive for muscle regeneration in preclinical models.

MGF: No established dose
TB-500: 2–5 mg SQ weekly
Context: Animal models only
Primary benefit: Satellite cell activation + enhanced migration/angiogenesis

PE 22-28

— no documented stacks