Long R3 IGF-I
Evidence: CGH Axis / Body Composition
Evidence Snapshot
What this grade covers
A for molecular identity; B/C for cell and animal pharmacology, including a hypoglycemia-relevant safety signal in animal models; E for human efficacy, approval, safety, performance, or dosing claims.
Regulatory Context
Not FDA-approved as a marketed human medicine; substance identity is recorded in FDA SRS. Prohibited in sport under WADA rules.
Research Takeaway
Long R3 IGF-I is an engineered insulin-like growth factor-I analog with altered sequence and markedly reduced affinity for IGF-binding proteins; it is not identical to native human IGF-I or FDA-approved recombinant IGF-I products, and mass-spectrometry-based anti-doping identity methods treat it as analytically distinct from Des(1-3)-IGF-I and R3-IGF-I.
Evidence boundary: Evidence for native IGF-I must not automatically be transferred to Long R3 IGF-I.
See all 6 evidence claims →Quick Summary
Long R3 IGF-I is an engineered analogue of insulin-like growth factor I developed largely for experimental and cell-culture applications. The audited evidence is predominantly animal and cell based; no verified controlled human administration trial was identified.
Mechanism & Research Overview
Long R3 IGF-I modifies native IGF-I with an Arg substitution near the N-terminus and an added N-terminal extension. These changes reduce binding to IGF-binding proteins while retaining IGF-receptor activity, but the practical evidence located here comes from cell and animal systems rather than therapeutic human trials.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Long R3 IGF-I is an engineered insulin-like growth factor-I analog with altered sequence and markedly reduced affinity for IGF-binding proteins; it is not identical to native human IGF-I or FDA-approved recombinant IGF-I products, and mass-spectrometry-based anti-doping identity methods treat it as analytically distinct from Des(1-3)-IGF-I and R3-IGF-I.
Does not establish
Evidence boundary: Evidence for native IGF-I must not automatically be transferred to Long R3 IGF-I.
Sources: Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs; Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig; Recombinant expression of IGF-1 and LR3 IGF-1 fused with collagen-binding domain in Pichia pastoris; Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection; Insulin-like growth factor I (IGF-I) and long R3IGF-I differently affect development and messenger ribonucleic acid abundance for IGF-binding proteins and type I IGF receptors in in vitro produced bovine embryos; Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes
Supported
Long R3 IGF-I has potent IGF-system biological activity in animal and cell models, including effects on tissue growth, metabolism, and modulation of the somatotropic (growth hormone/IGF) axis in juvenile animal models.
Does not establish
Evidence boundary: Preclinical anabolic activity does not establish human muscle-building efficacy or safety.
Sources: Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs; Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig; The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I
Supported
FDA enforcement records identify IGF1-LR3 compounded products as not qualifying for the cited section 503A exemptions and as not components of FDA-approved human drugs.
Does not establish
Evidence boundary: This does not describe lawful laboratory research use.
Supported
The frozen evidence package does not establish a controlled human therapeutic safety profile for Long R3 IGF-I; IGF-I analogues with markedly reduced IGF-binding-protein affinity, including Long R3 IGF-I-type variants, produced more potent and prolonged hypoglycemia than native IGF-I in pig and marmoset models.
Does not establish
Evidence boundary: This is an animal pharmacology finding, not a quantified human hypoglycemia rate, and it is not a basis for any consumer dosing statement.
Sources: Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs; Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig; IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys
Supported
No controlled human trial in this package establishes Long R3 IGF-I as a safe or effective bodybuilding, muscle-recovery, fat-loss, or anti-aging therapy.
Does not establish
Evidence boundary: Animal and laboratory data cannot be represented as human performance outcomes.
Sources: Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs; Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig; Recombinant expression of IGF-1 and LR3 IGF-1 fused with collagen-binding domain in Pichia pastoris
Supported
Only named research-study exposure may be presented, clearly labeled as preclinical where applicable; consumer dosing, reconstitution, and injection recommendations are prohibited.
Does not establish
Evidence boundary: Preclinical exposures must not be converted into human doses.
Sources: Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs; Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
The audited source set did not identify controlled human administration studies specific to Long R3 IGF-I.Safety Consideration
Animal experiments reported organ and gastrointestinal tissue growth and changes in endogenous IGF-axis markers.Safety Consideration
A prostate-cancer-cell study reported increased telomerase-related activity; this is a theoretical concern, not a measured human cancer risk.Safety Consideration
Direct LR3-specific clinical monitoring standards, contraindications, and long-term metabolic risks are not established.Safety Consideration
Non-approved products may have identity, potency, impurity, sterility, and labeling problems.Safety Consideration
Mechanism-based and product-quality concerns include severe hypoglycemia and insulin-like metabolic effects, electrolyte shifts, edema and fluid retention, headache and intracranial-pressure concerns, soft-tissue and organ growth, arthralgia and neuropathy, cardiac hypertrophy or arrhythmia, retinal and vascular effects, possible acceleration of existing malignancy or premalignant lesions, immunogenicity and anti-drug antibodies, misfolded disulfide isomers, aggregation and peptide-related impurities, sterility and endotoxin risks, interaction with insulin/GH/diabetes drugs, and unknown pregnancy, pediatric, reproductive, and long-term effects.
Research Areas Being Studied
Research areas discussed on this page reflect the GH Axis / Body Composition category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
No Human Study Findings Listed Yet
See preclinical, regulatory, and review sources below.
Study Tables by Evidence Type
Human Studies & Clinical Data
No Human Studies & Clinical Data Listed Yet
This section will be updated as sources are added.
Animal / Cell / Preclinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Recombinant expression of IGF-1 and LR3 IGF-1 fused with collagen-binding domain in Pichia pastoris | 2023 | The study separately produced human IGF-1 and Long R3 IGF-1, reinforcing that LR3 IGF-1 is an engineered analog rather than a synonym for native IGF-1. | |||
| LONG R3IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells | 2006 | HEK293 cell culture | The engineered analogue supported mammalian cell culture and was evaluated as an alternative to insulin in serum-free production conditions. | Industrial cell-culture utility does not establish safety or efficacy for administration to humans. | |
| Long R3 insulin-like growth factor-I enhances telomerase activity in human prostate cancer cells | 2003 | Human prostate cancer cell lines | Long R3 IGF-I exposure increased telomerase-related activity in the studied prostate cancer cells. | This cell-model result supports a theoretical concern about mitogenic signaling; it does not quantify cancer risk in people. | |
| Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose in rats | 2002 | Rats | Long R3 IGF-I increased intestinal glucose-analogue absorption, interpreted as likely reflecting increased mucosal mass. | This is an animal intestinal-growth/absorption finding, not evidence of human performance or body-composition benefit. | |
| Insulin-like growth factor I (IGF-I) and long R3IGF-I differently affect development and messenger ribonucleic acid abundance for IGF-binding proteins and type I IGF receptors in in vitro produced bovine embryos | 2001 | In vitro produced bovine embryos | Native IGF-I and Long R3 IGF-I had differing effects on bovine embryo development and on IGFBP/IGF-receptor mRNA abundance, consistent with Long R3 IGF-I's altered IGFBP-binding behavior. | In vitro embryo-model finding; no human reproductive or developmental safety inference should be drawn. | |
| IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys | 1997 | Pigs and marmoset monkeys | IGF-I analogues with reduced IGF-binding-protein affinity, including Long R3 IGF-I-type variants, produced more potent and prolonged hypoglycemia than native IGF-I in animal models. | Reduced IGFBP affinity is directly linked to a heightened hypoglycemic-risk signal in animals; this is a safety-relevant preclinical finding, not a human dosing guide. | |
| Long [R3] insulin-like growth factor-I reduces growth and plasma IGF binding protein-3 concentrations in growing pigs | 1997 | Pigs | Long R3 IGF-I is an engineered IGF-I analog with altered IGF-binding-protein interactions. Sustained exposure in pigs altered growth, food intake, and circulating IGF-system measures.
| The direction of growth and endocrine effects was not uniformly anabolic; extrapolation to humans is inappropriate. | |
| The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I | 1997 | Neonatal calves | Long R3 IGF-I administration modulated somatotropic-axis (GH/IGF) parameters in neonatal calves alongside nutrition and growth hormone. | Livestock/veterinary physiology model; not evidence of human efficacy or safety. | |
| Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection | 1996 | Animal model (rat) | Low-IGFBP-affinity IGF-I analogues retained superior potency relative to native IGF-I whether delivered by continuous infusion or bolus injection. | Route-of-administration comparison in animals; does not establish a human administration protocol. | |
| Administration of insulin-like growth factor-I (IGF-I) peptides selectively stimulates growth of the gastrointestinal tract in gut-resected, dexamethasone-treated, and normal rats | 1995 | Rat models | IGF-I peptides, including Long R3 IGF-I, selectively stimulated gastrointestinal tissue growth in multiple rat models. | Trophic effects on gastrointestinal tissues are preclinical and do not establish a therapeutic benefit or safety profile in humans. | |
| Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces circulating IGF-I in the guinea pig | 1995 | Guinea pigs | The study describes Long R3 IGF-I as an IGF-I analog with much reduced affinity for IGF-binding proteins and demonstrates potent organ-growth effects in guinea pigs.
| Systemic organ growth and suppression of endogenous IGF-axis measures are relevant preclinical safety signals; human relevance is unknown. | |
| Effects of Insulin-Like Growth Factor Binding Protein-3 on the Response of Cultured Chondrocytes to IGF-I and Long R3 IGF-I | In cultured cells, IGF-binding-protein-3 suppressed native IGF-I-stimulated proliferation more than Long R3 IGF-I-stimulated proliferation, consistent with Long R3 IGF-I's reduced IGFBP affinity. Cell-culture potency differences do not establish human efficacy, tissue selectivity, or safety. | ||||
| Novel Recombinant Fusion Protein Analogues of Insulin-Like Growth Factor (IGF)-I | The original engineering paper describes a family of related IGF-I muteins -- including Long IGF-I (N-terminal extension only), R3-IGF-I (Arg3 substitution only), Long R3 IGF-I (both modifications), and Long R3A16 IGF-I (an additional mutation) -- with differing IGF-binding-protein affinity and receptor potency. These related but distinct muteins must not be merged with one another or with native IGF-I. | ||||
| Solution Structure and Backbone Dynamics of Long-[Arg3]Insulin-Like Growth Factor-I | Structural analysis confirms the Arg3 substitution and 13-amino-acid N-terminal extension defining Long R3 IGF-I, and describes altered N-terminal conformation alongside preserved IGF-domain structure. This establishes molecular identity, not therapeutic benefit. | ||||
| The Disulfide Folding Pathway of Insulin-Like Growth Factor-I | Characterizes the disulfide folding pathway of Long R3 IGF-I, relevant to correct-vs-misfolded disulfide isomers as a manufacturing/product-quality concern for unapproved marketplace material. |
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| FDA Substance Registration System: LONG-(ARG3)INSULIN-LIKE GROWTH FACTOR-I | 2026 | Substance identity record | The FDA substance registry identifies LONG-(ARG3)INSULIN-LIKE GROWTH FACTOR-I under UNII M9L22Y19H9 and CAS 143045-27-6. | UNII assignment identifies a substance and does not indicate FDA approval, clinical effectiveness, or safety. | |
| Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes | 2021 | Analytical/anti-doping method development | Describes a mass-spectrometry method to distinguish and detect Long R3 IGF-I, Des(1-3)-IGF-I, and R3-IGF-I as analytically distinct entities for sports anti-doping testing. | Anti-doping analytical chemistry method; this is identity/detection context only, not efficacy or safety evidence, and it confirms Long R3 IGF-I and Des(1-3)-IGF-I are treated as analytically distinct molecules. | |
| Tailor Made Compounding LLC - Warning Letter | 2020 | FDA identified compounded IGF1-LR3, Cerebrolysin, PEG-MGF, and Melanotan II products that did not qualify for cited section 503A exemptions and were not components of FDA-approved human drugs. | |||
| WADA Research on Qualitative and Quantitative Determination of Insulin-Like Growth Factor-I (Including Long R3 IGF-I) | WADA-funded research specifically addresses analytical detection of IGF-I and Long R3 IGF-I in anti-doping testing. This is anti-doping analytical methodology, not a human administration, efficacy, or safety study. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Long R3 IGF-I is investigational and lacks a verified human clinical safety and effectiveness profile. This page is educational only, not medical advice, and not instructions for use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Content pending review. Last updated 2026-07-30.
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