91 amino acids

ExperimentalMuscle Building

IGF-1 LR3

Also known as: Long R3 IGF-1, LR3-IGF-1, Long Arg3 Insulin-like Growth Factor 1, IGF-1 Long R3, Receptor Grade IGF-1

Molecular weight
9111.40 Da
Formula
C400H625N111O115S9
CAS
946870-92-4
Routes
4

IGF-1 LR3 (Long R3 Insulin-like Growth Factor-1) is a modified version of human IGF-1, an 83-amino acid analog compared to the 70-amino acid native IGF-1. The modifications include substitution of glutamic acid at position 3 with arginine (R3) and addition of a 13-amino acid N-terminal extension peptide. These modifications dramatically reduce binding to IGF-binding proteins (IGFBPs), resulting in enhanced bioavailability and a 2-3 fold longer half-life than native IGF-1. Native IGF-1 circulates primarily bound to IGFBPs (especially IGFBP-3), which regulate its activity and limit tissue exposure. By evading IGFBP binding, IGF-1 LR3 remains in its free, biologically active form for extended periods, producing significantly more potent anabolic and metabolic effects than equivalent doses of native IGF-1. IGF-1 is the primary mediator of growth hormone's anabolic effects and is critical for muscle growth, fat metabolism, bone development, and tissue repair. IGF-1 LR3 was originally developed as a research tool for IGF-1 biology and is used in cell culture media to enhance cell proliferation. Its potent anabolic properties have attracted interest in muscle building, recovery, and age-related decline research.

For educational and research purposes only
Last updated:Check the research sources

Section 01

What it's used for

Muscle Growth and Size

IGF-1 LR3 is the most studied lab-made version of IGF-1 for growing skeletal muscle. Research shows it increases both muscle cell size and the number of muscle cells, producing dose-dependent increases in lean body mass and muscle area.

In vitroLimited data
Clinical wording

IGF-1 LR3 is the most extensively researched IGF-1 analog for skeletal muscle growth. It promotes both hypertrophy (increased cell size through protein synthesis) and hyperplasia (increased myonuclei through satellite cell activation). Research demonstrates dose-dependent increases in lean body mass and muscle cross-sectional area.

Lab Cell Culture Use

IGF-1 LR3 is mainly used in labs as a cell-culture additive, replacing serum for growing mammalian cells. It binds less to carrier proteins than natural IGF-1, making it more effective for cell growth. This is its main commercial use today.

In vitro
Clinical wording

IGF-1 LR3 is widely used as a cell culture supplement, replacing serum in media for mammalian cell growth. Its reduced IGFBP binding makes it more effective than native IGF-1 for supporting cell proliferation in vitro. This is its primary commercial application.

Muscle Wasting Research

In research on age-related muscle loss (sarcopenia) and disease-related muscle wasting, IGF-1 LR3 appears to counter muscle loss by activating the mTOR protein-building pathway and muscle repair (satellite) cells.

AnimalIn vitroLimited data
Clinical wording

Research in age-related sarcopenia and disease-related muscle wasting demonstrates IGF-1 LR3 can counteract muscle atrophy through mTOR-mediated protein synthesis and satellite cell activation.

Injury and Tissue Repair

IGF-1 signaling is studied for repairing muscle, tendon, and ligament injuries. It works by boosting protein building, cell growth, and production of the extracellular matrix, the structural material that supports tissue.

Limited data
Clinical wording

IGF-1 signaling promotes tissue repair in muscle, tendon, and ligament injuries through enhanced protein synthesis, cell proliferation, and extracellular matrix production.

Bone Growth and Density

IGF-1 is essential for building and maintaining bone. Research with IGF-1 LR3 shows increased growth of bone-building cells (osteoblasts) and more bone formation, with possible uses in osteoporosis and fracture healing.

Limited data
Clinical wording

IGF-1 is essential for bone development and maintenance. Research with IGF-1 LR3 demonstrates enhanced osteoblast proliferation and bone formation, with potential applications in osteoporosis and fracture healing.

Metabolism Research

IGF-1 LR3 is used in laboratory research to study insulin-like effects on metabolism, including how cells take up glucose and how growth-factor and metabolic signaling pathways interact together in both health and disease.

AnimalIn vitro
Clinical wording

IGF-1 LR3 is used to study insulin-like metabolic signaling, glucose uptake, and the interplay between growth factor and metabolic pathways in health and disease.

Section 02

Mechanism of Action

Mechanism 01

Switching on the growth receptor

  • It binds the IGF-1 receptor, a four-part switch sitting in the cell membrane.
  • Binding makes the receptor tag itself and recruit adaptor proteins inside the cell.
  • Two cascades follow: one for survival and metabolism, one for cell multiplication.
Clinical wording

IGF-1 Receptor Activation

IGF-1 LR3 binds to the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase heterotetrameric receptor (α2β2). Ligand binding activates the intrinsic tyrosine kinase of the β-subunits, triggering autophosphorylation and recruitment of insulin receptor substrate (IRS) proteins. This initiates two major downstream signaling cascades: PI3K/Akt/mTOR (metabolic/survival) and Ras/MAPK (proliferative).

Mechanism 02

Escaping the proteins that hold it

  • Over 99 percent of natural IGF-1 is bound to six carrier proteins that limit its activity.
  • This modified version binds those carriers far less and circulates mostly free.
  • At the receptor it is reported as two to three times more potent than natural IGF-1.
Clinical wording

Enhanced Bioavailability

The key pharmacological advantage of IGF-1 LR3 over native IGF-1 is its greatly reduced binding to the six IGF-binding proteins (IGFBPs 1-6). Normally, >99% of circulating IGF-1 is bound to IGFBPs, which limit its bioactivity. IGF-1 LR3 circulates predominantly in free form, providing 2-3 times the potency of native IGF-1 at the receptor level.

Mechanism 03

Turning up the protein factory

  • The survival cascade activates a master growth switch called mTOR inside the cell.
  • That switch releases the cell's protein-making machinery by acting on two control proteins.
  • Raised protein production is described as the main driver of this peptide's muscle-building action.
Clinical wording

mTOR-Mediated Protein Synthesis

Through the PI3K/Akt/mTOR pathway, IGF-1 LR3 activates the mechanistic target of rapamycin (mTOR), which phosphorylates p70S6K and 4E-BP1. This dramatically enhances ribosomal protein synthesis, driving muscle protein accretion and cell growth. mTOR activation is the primary mechanism of IGF-1 LR3's anabolic effects.

Mechanism 04

Waking muscle's own repair cells

  • It activates satellite cells, the stem cells sitting alongside skeletal muscle fibres.
  • Those cells multiply, mature and fuse into existing fibres, adding new nuclei.
  • Adding nuclei differs from simply enlarging fibres, the usual route for anabolic agents.
Clinical wording

Satellite Cell Activation

IGF-1 LR3 activates skeletal muscle satellite cells (muscle stem cells), promoting their proliferation, differentiation, and fusion with existing myofibers. This hyperplastic growth mechanism (increasing the number of myonuclei) distinguishes IGF-1 from other anabolic agents that primarily produce hypertrophic growth.

Mechanism 05

Keeping cells from self-destructing

  • The activated survival enzyme switches off three proteins that would trigger cell death.
  • Blocking that death programme is described as contributing to tissue protection and regeneration.
Clinical wording

Anti-Apoptotic Signaling

Akt activation by IGF-1 LR3 phosphorylates and inactivates pro-apoptotic proteins (Bad, caspase-9, FKHR), promoting cell survival. This anti-apoptotic effect contributes to tissue protection and regeneration.

Section 03

Biological Pathways

  1. PI3K/Akt/mTOR Anabolic PathwayIGF-1R→IRS-1→PI3K→Akt→mTORC1→p70S6K/4E-BP1 is the master anabolic cascade, enhancing protein synthesis via S6 kinase and eIF4E while suppressing degradation via autophagy/FOXO inhibition.
  2. Ras/Raf/MEK/ERK Proliferation PathwayIGF-1R→Shc→Grb2→SOS→Ras→Raf→MEK→ERK1/2 drives cell proliferation, differentiation, and gene expression, and is critical for satellite cell proliferation and IGF-1's mitogenic effects.
  3. FOXO Protein Degradation InhibitionAkt phosphorylates FOXO1/FOXO3, excluding them from the nucleus and blocking transcription of atrophy genes MuRF1 and atrogin-1/MAFbx, reducing muscle protein breakdown.
  4. GSK-3β/Glycogen SynthesisAkt phosphorylates and inactivates GSK-3β, relieving inhibition of glycogen synthase and promoting glycogen storage in muscle and liver.

Section 04

Dosage Information

Amino acid sequence
MFPAMPLSSL FVNGPRTLCG AELVDALQFV CGDRGFYFNK PTGYGSSSRR APQTGIVDEC CFRSCDLRRL EMYCAPLKPA KSA
Ranges reported in experimental work
Route / systemContextRange studiedLimitation
Subcutaneous — mecasermin (rhIGF-1)FDA label, severe IGF-1 deficiency in children0.04–0.08 mg/kg twice a day to start, up to 0.12 mg/kg twice a day — 2.8–8.4 mg per dose at 70 kg, each within ±20 min of a mealMecasermin is native IGF-1, not LR3, and it treats growth failure in children whose blood sugar is watched. The label warns of seizures from low blood sugar.
Intravenous — animal infusionRat and guinea pig growth models — the only LR3 dosingRats: 2.5 mg/kg a day infused for 3 days. Guinea pigs: 120 µg a day for 7 days — about 340 µg/kg a day at 350 g body weightA pump running around the clock in a rodent, not a daily injection. Nobody converted these into a human dose, and what grew was gut and organs, not muscle.
Subcutaneous — self-administrationCirculating practice; no human study of LR320–100 µg per day, most often 40–50 µg, in 4–6 week cycles — roughly 0.2–1.4 µg/kg a day for a 70–90 kg adultCirculating practice, not a finding. It carries mecasermin's low-blood-sugar risk without the meal rule, and at a 20–30 hour half-life doses overlap.
Intramuscular — into the trained musclePractice claim of growth at the injection siteThe same 20–100 µg per day, put into the muscle just trained or split morning and evening; no separate amount is namedGrowth at the injection site has never been tested for LR3 in a person. It binds carrier proteins weakly and lasts 20–30 hours, so it acts body-wide.
Dosage calculatorMass · concentration · volume · U-100

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Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.

Section 05

Protocols

  1. Protocol 01

    IGF-1 LR3 Muscle Growth Protocol

    Potent muscle building protocol using extended half-life IGF-1. For experienced users only.

    Focus
    Sport & Performance
    Level
    Advanced
    Duration
    4–6 weeks
    View Full Protocol
  2. Protocol 02

    IGF-1 LR3 + PEG-MGF Advanced Stack

    Maximum muscle growth stack combining systemic IGF-1 with localized MGF for hypertrophy and repair.

    Focus
    Sport & Performance
    Level
    Advanced
    Duration
    6–8 weeks
    View Full Protocol

Section 06

Stability & Storage

  1. Lyophilised powder

    IGF-1 LR3 is more prone to degradation than smaller peptides. Kept at −20 °C or below for long-term stability (12–18 months); at 2–8 °C, the lyophilised powder only stays stable for about 1–3 months.

  2. After reconstitution

    Dissolved in 0.1M acetic acid or sterile water with 0.1% BSA rather than bacteriostatic water, whose benzyl alcohol can trigger protein aggregation, and mixed with gentle swirling rather than vortexing or shaking it. The solution is kept at 2–8 °C, used within 14–21 days, and not put through repeated freeze-thaw cycles.

Section 07

Side Effects & Precautions

IGF-1 LR3's side effects follow from its strong, sustained activation of IGF-1 and insulin receptors: swings in blood sugar, tissue and organ growth, and a cancer-risk concern shared with the body's own growth signaling.

  1. Blood sugar effects in both directions

    • At high concentrations, IGF-1 LR3 activates the insulin receptor and boosts glucose uptake via IGF-1R/Akt/GLUT4 signaling.
    • This can cause significant low blood sugar (hypoglycemia), especially combined with insulin or during fasting.
    • Symptoms of low blood sugar include shakiness, sweating, confusion, and, in severe cases, loss of consciousness.
    • With chronic high-dose use, this can paradoxically flip into insulin resistance through cross-desensitization of the IGF-1 and insulin receptors.
  2. Organ and bone growth

    • Chronic high-dose use can enlarge organs — including the intestines, spleen, and heart — an effect that is dose-dependent and more concerning with prolonged use.
    • Prolonged high IGF-1 exposure can cause acromegaly-like features: growth of the jaw, hands, and feet from bone growth and soft-tissue expansion.
  3. Joint pain and fluid retention

    • GH/IGF-1-mediated effects on connective tissue can cause joint pain (arthralgia); combined with tissue growth effects, it is commonly reported.
    • IGF-1 promotes sodium retention by the kidneys, causing fluid buildup in the extremities and face.
  4. Tumor growth concern

    IGF-1 signaling promotes cell proliferation and blocks programmed cell death (apoptosis) — the pathways cancer cells use. Elevated IGF-1 levels are epidemiologically linked to higher risk of breast, prostate, and colon cancer; use is contraindicated in people with known or suspected malignancies.

Section 08

Regulatory Status

IGF-1 LR3 has no approval anywhere in the world for use in humans — not from the FDA, not from any other national regulator — even though the natural hormone it modifies does have one narrow approved use.

WADA treats it as a banned growth factor regardless.

  1. FDA / United States

    Not approved for any human use

    No regulator has approved IGF-1 LR3 itself for human therapeutic use. The only FDA-approved IGF-1 product is mecasermin (Increlex), a different, unmodified molecule approved solely for severe primary IGF-1 deficiency in children — an approval that does not extend to IGF-1 LR3.

  2. Marketed use

    Sold only as a research reagent

    Biotechnology suppliers sell IGF-1 LR3 as a laboratory reagent and cell-culture supplement, explicitly not for human consumption. Products sold this way carry none of the purity, dosing, or manufacturing oversight a therapeutic approval would require.

  3. WADA

    Prohibited under category S2

    WADA bans IGF-1 and all of its analogs, IGF-1 LR3 included, under S2.2 of the Prohibited List — Peptide Hormones, Growth Factors, Related Substances and Mimetics — at all times, in and out of competition, with no exemption for an unapproved product.

The «research use only» label on IGF-1 LR3 products does not turn them into approved medicines and says nothing about their purity or origin. Regulatory status differs between jurisdictions and changes over time; check the current documents of your own regulator before relying on any of this.

Section 09

Research Studies

  1. [1]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 potencyFrancis GL, Ross M, Ballard FJ, et al. · Journal of Molecular Endocrinology · 1992
  2. [2]Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injectionTomas FM, Lemmey AB, Read LC, et al. · Journal of Endocrinology · 1996
  3. [3]Molecular and Cellular Aspects of the Insulin-Like Growth Factor I ReceptorLeRoith D, Werner H, Beitner-Johnson D, et al. · Endocrine Reviews · 1995
  4. [4]Cellular Actions of the Insulin-Like Growth Factor Binding ProteinsFirth SM, Baxter RC · Endocrine Reviews · 2002
  5. [5]Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathwaysRommel C, Bodine SC, Clarke BA, et al. · Nature Cell Biology · 2001
  6. [6]Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic modelsSchiaffino S, Mammucari C · Skeletal Muscle · 2011
  7. [7]Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscleMusarò A, McCullagh K, Paul A, et al. · Nature Genetics · 2001
  8. [8]Satellite cell proliferation and skeletal muscle hypertrophyAdams GR · Applied Physiology, Nutrition, and Metabolism · 2006
  9. [9]IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscleChakravarthy MV, Davis BS, Booth FW · Journal of Applied Physiology · 2000
  10. [10]Multiple Signaling Pathways of the Insulin-Like Growth Factor 1 Receptor in Protection from ApoptosisPeruzzi F, Prisco M, Dews M, et al. · Molecular and Cellular Biology · 1999

Section 10

Frequently Asked Questions

No human trial has tested IGF-1 LR3 for muscle growth — the compound was developed, and is still mainly used, as a cell-culture supplement to keep cells growing in the lab. The mechanistic case (activating IGF-1 receptors, driving mTOR-mediated protein synthesis and satellite-cell activation) is solid in isolated cells, and the only whole-animal dosing is rat and guinea-pig infusion studies that grew gut and organs, not muscle. What circulates as evidence for physique use is extrapolation from that biology, not a measured outcome in a person.

This is a real epidemiological concern rather than a settled one. IGF-1 signalling promotes cell proliferation and blocks programmed cell death — the same pathways cancer cells exploit — and elevated circulating IGF-1 is associated with increased risk of breast, prostate and colon cancer in observational studies. On that basis, use by anyone with a known or suspected malignancy is considered contraindicated, though no study has directly measured cancer incidence from IGF-1 LR3 use specifically.

The only FDA-approved human dosing in this family is for mecasermin (Increlex), which is native IGF-1, not LR3, given to children with severe IGF-1 deficiency at 0.04–0.12 mg/kg twice daily around meals to manage the seizure risk from low blood sugar. IGF-1 LR3 itself has no human dosing study at all — the 20–100 µg a day figure circulating in practice is self-reported use, not a research finding, and it carries mecasermin's hypoglycemia risk without the meal-timing rule that manages it.

IGF-1 LR3 has no FDA or other regulatory approval for human use anywhere; it is sold and classified as a research reagent and cell-culture supplement. WADA prohibits IGF-1 and all its analogues, including LR3, under category S2, banned both in and out of competition.

The most significant documented risk is hypoglycemia: at the concentrations reached with LR3, the peptide activates the insulin receptor directly and drives glucose uptake through IGF-1R/Akt/GLUT4 signalling, an effect that intensifies when combined with insulin or during fasting. Chronic high-dose use is also linked to organ enlargement (intestinal, splenic, cardiac hypertrophy), joint pain and, with prolonged exposure, acromegaly-like growth of the jaw, hands and feet.

IGF-1 LR3 degrades faster than smaller peptides: as lyophilised powder it holds up 12–18 months at −20 °C, but only about 1–3 months at 2–8 °C. It is reconstituted with 0.1M acetic acid or sterile water with 0.1% BSA rather than bacteriostatic water, whose benzyl alcohol can make the protein clump, mixed by gentle swirling, and used within 14–21 days without repeated freeze-thaw cycles.

This claim, about injecting into a just-trained muscle for localized growth, has never been tested for LR3 in a person. The peptide binds carrier proteins only weakly and has a 20–30 hour half-life, so pharmacologically it circulates and acts throughout the body rather than staying at the injection site.