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Muscle Biology and Hypertrophy Research: Growth Factor Analogues and Myostatin Regulators

Editorial note: this article summarises published research on growth factor analogues and myostatin regulators. Baclabs does not sell these compounds or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.

The compounds marketed as muscle growth peptides, somatropin, IGF-1 LR3, IGF-1 DES, MGF, PEG-MGF and follistatin-344, sit at wildly different points on the evidence scale. One of them is a licensed medicine with decades of controlled trial data. One is a licensed medicine’s close cousin. The rest have never been given to a human being in a published, controlled hypertrophy trial. That gap is the single most important thing to understand before reading anything else about this class.

This hub explains the biology properly: how the growth hormone (GH) to insulin-like growth factor 1 (IGF-1) axis actually drives protein accretion, what the satellite cell pool contributes to muscle remodelling, and how myostatin acts as a brake on that system. It then works compound by compound, separating what has been demonstrated in humans from what has been demonstrated in rodents, in cell culture, or nowhere at all.

Four supporting articles go deeper: IGF-1 LR3 vs IGF-1 DES, MGF vs PEG-MGF, follistatin-344 and myostatin inhibition, and somatropin dosing and HGH reconstitution maths.

What the term “muscle growth peptides” actually covers

The phrase is a marketing bucket, not a pharmacological class. It contains at least four mechanistically distinct things:

  • Recombinant hormones. Somatropin is recombinant human growth hormone (HGH), a 191-amino-acid protein identical to the pituitary hormone. It is a prescription-only medicine in the UK with a full Summary of Product Characteristics (SmPC) [5][6].
  • Growth factor analogues. IGF-1 LR3 and IGF-1 DES are engineered variants of IGF-1 designed to evade the IGF binding proteins (IGFBPs) that normally sequester circulating IGF-1 [1][2][3].
  • Splice-variant fragments. MGF (mechano growth factor) is the E-domain of the IGF-1Ec splice variant; PEG-MGF is that fragment with a polyethylene glycol chain attached [11][12].
  • Pathway inhibitors. Follistatin-344 binds and neutralises myostatin and activins, releasing a brake on muscle growth rather than pressing an accelerator [9][10].

Only the first category has a licensed product behind it. Recombinant IGF-1 also exists as a licensed medicine, mecasermin (Increlex), but it is licensed for severe primary IGF-1 deficiency in children, not for hypertrophy, and the analogues sold online are not mecasermin [4].

The GH–IGF-1 axis, briefly and accurately

The hypothalamus releases growth hormone-releasing hormone (GHRH), which triggers pulsatile GH secretion from the anterior pituitary. GH acts directly on tissues and indirectly by stimulating hepatic production of IGF-1. IGF-1 circulates almost entirely bound to a family of six IGF binding proteins, predominantly IGFBP-3 in a ternary complex with the acid-labile subunit. That binding is not incidental: it extends IGF-1’s half-life from minutes to hours while keeping free, receptor-active IGF-1 tightly restricted.

At the muscle fibre, IGF-1 receptor activation drives the PI3K/Akt/mTOR pathway, increasing protein synthesis, and simultaneously suppresses the FoxO-driven atrogene programme that degrades muscle protein. In parallel, mechanical loading and injury activate satellite cells, the resident muscle stem cells, which proliferate, fuse with existing fibres and donate myonuclei. Hypertrophy in adults involves both arms.

Myostatin (GDF-8) works against this. Secreted by muscle itself, it signals through the activin type IIB receptor and Smad2/3 to limit fibre growth. Humans with loss-of-function myostatin mutations are strikingly muscular: the 2004 case report by Schuelke and colleagues in the New England Journal of Medicine described a child with gross muscle hypertrophy and a myostatin splice-site mutation [14]. That case is the origin of essentially all commercial interest in myostatin inhibition.

Somatropin (HGH): the licensed anchor point

Somatropin is licensed in the UK for paediatric growth failure across several indications (GH deficiency, Turner syndrome, chronic renal insufficiency, small-for-gestational-age short stature, Prader-Willi syndrome) and, in adults, as replacement therapy for pronounced GH deficiency [5]. It is not licensed anywhere for athletic performance or body composition in healthy people.

Adult replacement doses are small. The Genotropin SmPC gives 0.15–0.3 mg per day for adult-onset GH deficiency, titrated against IGF-1 concentrations, with maintenance rarely exceeding 1.0 mg/day and lower starting doses over age 60 [5]. Norditropin gives 0.1–0.3 mg/day for adult-onset disease, and states plainly that 1 mg of somatropin corresponds to 3 IU [6], the conversion that underpins all HGH reconstitution arithmetic.

The performance evidence in healthy adults is unimpressive. A systematic review of 27 randomised trials in 440 participants found lean body mass increased by about 2.1 kg relative to controls, with no statistically significant improvement in quadriceps or biceps strength and no gain in VO2max or exercise capacity. Adverse events were markedly more frequent in the GH arms: soft tissue swelling in 44% versus 1%, fatigue in 35% versus 0% [7][8]. Increased lean mass in that setting largely reflects fluid retention rather than contractile tissue.

The full dosing detail, the IU-to-milligram conversion and worked reconstitution tables for 10 IU and 12 IU vials are in the somatropin and HGH reconstitution article.

IGF-1 LR3 and IGF-1 DES: engineered to escape the binding proteins

Both analogues exist for the same reason, to reduce IGFBP capture and so raise free, receptor-active growth factor.

IGF-1 LR3 (Long R3 IGF-1) substitutes arginine for glutamate at position 3 and adds a hydrophobic 13-amino-acid N-terminal extension, taking the chain from 70 to 83 residues. Francis and colleagues, who designed it in 1992, concluded that the analogue’s greater potency came from reduced IGF-binding-protein capture rather than tighter receptor binding [3]. In a guinea pig infusion study, Long R3 IGF-I increased the fractional weight of adrenals, gut, kidneys and spleen without raising total circulating IGF concentrations [1], note that the tissues that responded were viscera, not skeletal muscle.

IGF-1 DES (des(1-3)IGF-1) is the opposite design: rather than adding, it removes the N-terminal tripeptide Gly-Pro-Glu. It occurs naturally, having been isolated from bovine colostrum, human brain and porcine uterus, and is roughly 10-fold more potent than IGF-1 at stimulating hypertrophy and proliferation of cultured cells, because loss of the position-3 glutamate reduces IGFBP binding [2].

Neither has published controlled human hypertrophy data. The comparison, the claimed protocols and the reasons the “local site growth” idea is weaker than it sounds are covered in IGF-1 LR3 vs IGF-1 DES.

MGF and PEG-MGF: an appealing story with contradictory data

Mechanical loading shifts IGF-1 splicing towards the IGF-1Ec isoform, whose distinct C-terminal E-domain, dubbed mechano growth factor by Goldspink’s group, was proposed to activate satellite cells before being processed to mature IGF-1. The hypothesis is elegant, and it is why MGF is marketed as a post-workout satellite cell agent.

The direct evidence for the synthetic E-peptide is poor. Fornaro and colleagues, publishing in American Journal of Physiology, Endocrinology and Metabolism in 2014, reported that the MGF peptide had no apparent effect on myoblasts or primary muscle stem cells [12][13]. Janssen and colleagues found in 2016 that full-length MGF activates the IGF-1 receptor to a similar maximum as IGF-1 but with roughly nine-fold lower potency (EC50 7.83 versus 0.86 nmol/L), while the synthetic E-peptides, including the Goldspink-MGF construct, produced no IGF-1 receptor activation at all [11].

PEG-MGF adds a pegylation step intended to extend circulating half-life. We could not locate any published human pharmacokinetic or efficacy study of PEG-MGF. See MGF vs PEG-MGF for the full appraisal.

Follistatin-344 and myostatin inhibition

Follistatin is an activin-binding glycoprotein [20] that also neutralises myostatin. FST-344 is the precursor transcript that yields the longer circulating FST-315 isoform; FST-288 is the shorter, cell-surface-associated form, and a follistatin-288-Fc fusion has been shown to promote localised skeletal muscle growth in preclinical work [21].

The headline human study is a gene therapy trial, not a peptide study. Mendell and colleagues delivered AAV1-FS344 by direct intramuscular injection into the quadriceps of six ambulatory Becker muscular dystrophy patients at 3 × 10¹¹ or 6 × 10¹¹ vector genomes per kg per leg, and reported a statistically significant mean 11.5% improvement in six-minute walk distance at six months, with no adverse effects attributable to gene transfer [9][10]. That is an AAV vector causing muscle cells to manufacture follistatin locally and continuously, not the same intervention as injecting follistatin protein.

Across the wider myostatin field, human results have been sobering: muscle volume gains of 3–9% (against 10–30% in mice) that generally did not translate into clinically meaningful strength or function, and the decoy receptor ACE-031 was discontinued after epistaxis and telangiectasias attributed to off-target BMP-9/BMP-10 inhibition [15]. Details in the follistatin-344 article.

Evidence at a glance

Compound Mechanism Best human evidence Licensed?
Somatropin (HGH) GH receptor; hepatic and local IGF-1 Multiple RCTs; +2.1 kg lean mass, no strength gain in healthy adults [7] Yes, POM, GH deficiency and paediatric indications [5][6]
Mecasermin (rhIGF-1) IGF-1 receptor Paediatric growth trials in severe primary IGF-1 deficiency [4] Yes, POM, not for hypertrophy
IGF-1 LR3 IGF-1R; reduced IGFBP affinity None published for human hypertrophy; animal and cell data only [1][3] No
IGF-1 DES IGF-1R; ~10× potency in cell culture None published for human hypertrophy [2] No
MGF / PEG-MGF IGF-1Ec E-domain; receptor unresolved None; in vitro results conflict [11][12] No
Follistatin-344 Myostatin and activin binding AAV gene therapy trial only, n=6 [9][10] No

Safety signals worth taking seriously

IGF-1 and its analogues are insulin-like by design. The Increlex product information requires dosing shortly before or after a meal, warns against high-risk activity for 2–3 hours after a dose, and instructs families in glucagon use for severe hypoglycaemia; tonsillar hypertrophy (9%), injection-site lipohypertrophy (17%), intracranial hypertension and post-marketing neoplasm reports are also documented [4]. Analogues engineered specifically to evade the binding proteins that normally buffer IGF-1 should be assumed to carry at least this hypoglycaemia risk, and no dosing framework exists to manage it.

Somatropin’s adverse effect profile is dose-related and well characterised: peripheral oedema is very common, with arthralgia, myalgia, joint stiffness, paraesthesia, carpal tunnel syndrome and type 2 diabetes mellitus all listed [6]. Supraphysiological use amplifies all of these.

Unlicensed compounds carry an additional problem that has nothing to do with pharmacology: you cannot verify what is in the vial. Purity, correct sequence, endotoxin load and actual peptide content are all unknown outside a certificate of analysis you can independently corroborate.

Anti-doping status

Everything on this page is prohibited in sport at all times. WADA section S2 covers growth hormone and its analogues and fragments, IGF-1 (mecasermin) and its analogues, and mechano growth factors, all as non-specified substances [16][18]. Section S4 covers myostatin inhibitors explicitly, including “myostatin-binding proteins (e.g. follistatin, myostatin propeptide)” and decoy activin receptors such as ACE-031 [17]. Analytical methods for full-length MGF in doping control have been published [19].

Reconstitution and diluent choice

Every compound here except licensed pen-based somatropin arrives as a lyophilised powder that must be reconstituted before use, and multi-dose vials need a preserved diluent so repeated punctures do not seed microbial growth. Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials; the reconstitution guide sets out the concentration maths, and the bacteriostatic versus sterile water comparison explains when a preservative is and is not appropriate. Once punctured, a preserved vial is generally treated as usable for up to 28 days, see storage and shelf life for how that rule works in practice.

Licensed somatropin presentations are different: Genotropin’s two-chamber cartridge supplies its own solvent and the reconstituted product is stable for 28 days at 2–8 °C [5]. Where a manufacturer provides a diluent, that diluent is the one the stability data was generated with.

Frequently asked questions

Do muscle growth peptides actually build muscle?

Only somatropin has controlled human data, and it increases lean body mass by around 2.1 kg without improving strength or exercise capacity, a change dominated by fluid retention [7]. IGF-1 LR3, IGF-1 DES, MGF, PEG-MGF and follistatin-344 have no published controlled human hypertrophy trials at all. Anything claiming otherwise is extrapolating from rodents or cell culture.

Is IGF-1 LR3 stronger than HGH?

They act at different points. Somatropin works through the GH receptor and raises IGF-1 indirectly; IGF-1 LR3 hits the IGF-1 receptor directly and evades the binding proteins that normally restrain it [3]. “Stronger” is not measurable here because there is no human trial comparing them for muscle outcomes, and the licensed IGF-1 product is mecasermin, not LR3 [4].

What is the difference between MGF and PEG-MGF?

PEG-MGF is the same E-domain peptide with a polyethylene glycol chain attached to slow clearance. The pegylation is a formulation change, not a mechanistic one, and no published human pharmacokinetic study of PEG-MGF appears to exist. The underlying peptide’s activity is itself disputed [11][12].

Does follistatin-344 injection work like the gene therapy trial?

No. The Becker muscular dystrophy trial used an AAV1 vector injected into quadriceps muscle so that muscle cells produced follistatin continuously in situ [9][10]. Injecting follistatin protein delivers a short-lived systemic exposure with entirely different pharmacokinetics, and it has not been tested in that form.

Are these compounds legal in the UK?

Somatropin and mecasermin are prescription-only medicines, supplied via a prescriber. IGF-1 LR3, IGF-1 DES, MGF, PEG-MGF and follistatin-344 hold no UK marketing authorisation; selling or supplying them for human use engages the Human Medicines Regulations 2012 and MHRA enforcement. All are banned in sport at all times [16][17].

How many IU are in a milligram of HGH?

Three. The Norditropin SmPC states that 1 mg of somatropin corresponds to 3 IU [6]. A 10 IU vial therefore contains about 3.33 mg and a 12 IU vial 4 mg. Worked reconstitution tables for both vial sizes are in the somatropin article.

References

  1. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig. Journal of Endocrinology, 1995
  2. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Cytokine & Growth Factor Reviews, 1996
  3. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. Francis GL et al. Journal of Molecular Endocrinology, 1992
  4. Increlex (mecasermin) Summary of Product Characteristics. European Medicines Agency
  5. Genotropin 12 mg powder and solvent for solution for injection, SmPC. electronic medicines compendium
  6. Norditropin FlexPro 10 mg/1.5 ml solution for injection, SmPC. electronic medicines compendium
  7. Systematic review: the effects of growth hormone on athletic performance (DARE structured abstract). NIHR Centre for Reviews and Dissemination
  8. Liu H et al. Systematic review: the effects of growth hormone on athletic performance. Annals of Internal Medicine, 2008
  9. Al-Zaidy SA et al. Follistatin gene therapy improves ambulation in Becker muscular dystrophy. Journal of Neuromuscular Diseases, 2015
  10. Mendell JR et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Molecular Therapy, 2015
  11. Janssen JAMJL et al. Potency of full-length MGF to induce maximal activation of the IGF-I R is similar to recombinant human IGF-I at high equimolar concentrations. PLOS ONE, 2016
  12. Fornaro M et al. Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells. American Journal of Physiology, Endocrinology and Metabolism, 2014
  13. Same article, publisher full text. American Physiological Society, 2014
  14. Schuelke M et al. Myostatin mutation associated with gross muscle hypertrophy in a child. New England Journal of Medicine, 2004
  15. Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases. PMC, 2022
  16. WADA Prohibited List S2: Peptide hormones, growth factors, related substances and mimetics. Drugs.com summary of the WADA list
  17. WADA Prohibited List S4: Hormone and metabolic modulators. Drugs.com summary of the WADA list
  18. The Prohibited List. World Anti-Doping Agency
  19. Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls. Growth Hormone & IGF Research, 2014
  20. Follistatin and its role as an activin-binding protein. PubMed, 1997
  21. Follistatin-288-Fc fusion protein promotes localized growth of skeletal muscle. PubMed, 2019

Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.