recoveryIGF-1 analog

IGF-1 LR3

IGF-1 LR3 (Long R3 IGF-1) is an engineered analog of human insulin-like growth factor 1. It takes the 70 amino acid native peptide, substitutes arginine for glutamic acid at position 3, and adds a 13 residue N-terminal extension, giving an 83 amino acid protein of roughly 9.1 kDa. Both modifications exist for one purpose: to stop the molecule binding to the IGF binding proteins (IGFBPs) that normally sequester more than 95 percent of circulating IGF-1. The result is a peptide that reaches the IGF-1 receptor in a far higher free fraction than the native hormone.

class
recombinant IGF-1 analog, 83 amino acids, about 9.1 kDa
modification
Arg substituted for Glu at position 3, plus a 13-residue N-terminal extension
route
subcutaneous, sites rotated
typical dose
20–50 mcg per day in self-directed protocols (no clinical dosing standard exists)
plasma half-life
shorter than native IGF-1, not the 20–30 hours commonly repeated online (see FAQ)
storage
lyophilized refrigerated 2–8°C; reconstituted with BAC water, 2–8°C, 28-day max
regulatory
sold as a cell culture reagent, not approved for human use, WADA prohibited (S2)
Dose calculatorlive
U-100
Concentration
0.50mg/mL
Injection vol.
0.080mL
Syringe cap.
100units
Draw to8.0units
0204060801008.0 units
Dosing guide

IGF-1 LR3 Reconstitution & Dosage Protocol

weekly dose · reduces side effects
PhaseWindowWeekly doseDraw (U-100, 2mL BAC)Note
Reconstitution + baselineDay 00.00 mg0 units· 0.00 mLReconstitute 1 mg in 2 mL bacteriostatic water for 500 mcg/mL. At that concentration 20 mcg is 0.04 mL (4 units on a U-100 syringe) and 40 mcg is 0.08 mL (8 units). Going to 1 mL of BAC water doubles the concentration and halves those unit counts, which makes small doses harder to measure accurately, so 2 mL is the better choice here. Baseline fasting glucose and HbA1c matter more for this compound than for any GH secretagogue on this site, because IGF-1 has direct insulin-receptor activity
Tolerance startDays 1–50.02 mg4 units· 0.04 mL20 mcg once daily, which is 4 units at 500 mcg/mL. The point of the low opening block is hypoglycemia: IGF-1 binds the insulin receptor with roughly a hundredth the affinity of insulin, but at these doses that is not zero. Inject with a meal containing carbohydrate and protein rather than fasted, which is the opposite of GHRP timing, and keep fast-acting carbohydrate available
Standard dailyDays 6–280.04 mg8 units· 0.08 mL40 mcg once daily (8 units at 500 mcg/mL), the most commonly used self-directed dose. Post-workout or with a post-workout meal is the usual timing. Doses above 50 mcg per day appear frequently in forum protocols and have no supporting human data, only a higher hypoglycemia risk
WashoutDays 29–560.00 mg0 units· 0.00 mLFour weeks off. The rationale is receptor downregulation and the general principle of not sustaining supraphysiologic IGF-1 signaling, though the specific 4-on/4-off pattern is convention rather than something anyone has tested. Recheck fasting glucose here
ReassessAfter week 80.00 mg0 units· 0.00 mLDecide from objective markers (bodyweight trend, strength logs, fasting glucose, HbA1c), not perceived pump or fullness, which is largely the compound driving glucose uptake into muscle and is not a proxy for tissue accrual. Anyone with a personal or family cancer history, active neoplasia, or proliferative retinopathy should not restart: IGF-1 receptor signaling is mitogenic and anti-apoptotic by design
How it works

What is IGF-1 LR3?

IGF-1 LR3 (Long R3 IGF-1) is an engineered analog of human insulin-like growth factor 1. It takes the 70 amino acid native peptide, substitutes arginine for glutamic acid at position 3, and adds a 13 residue N-terminal extension, giving an 83 amino acid protein of roughly 9.1 kDa. Both modifications exist for one purpose: to stop the molecule binding to the IGF binding proteins (IGFBPs) that normally sequester more than 95 percent of circulating IGF-1. The result is a peptide that reaches the IGF-1 receptor in a far higher free fraction than the native hormone.

That design comes out of a specific line of work. Francis and colleagues, publishing in the Journal of Molecular Endocrinology in 1992, built a series of N-terminal fusion analogs precisely to separate two variables: how tightly an IGF binds its receptor versus how tightly it binds IGFBPs. Their finding was that reduced IGFBP affinity, not enhanced receptor affinity, is what drives the potency increase. LR3 actually binds the IGF-1 receptor slightly less well than native IGF-1. It is more potent in cell systems anyway, because far more of it is free to act.

The in vivo evidence is almost entirely rodent. Tomas and colleagues (Biochem J, 1992) showed IGF-1 variants with reduced IGFBP binding were markedly more anabolic than native IGF-1 in dexamethasone-treated rats, and related work from the same group found the analogs drove pronounced gut growth. Ballard and colleagues (Growth Regul, 1993) then made the tradeoff explicit: escaping IGFBP binding also removes the reservoir that keeps native IGF-1 in circulation, so these analogs are cleared from plasma faster, not slower. That single result is the reason the "20 to 30 hour half-life" figure that circulates in peptide forums is backwards relative to the primary data.

There is no human clinical program for LR3 specifically. The relevant human safety data comes from mecasermin, recombinant native human IGF-1, which is approved for severe primary IGF-1 deficiency and Laron syndrome. A 2021 European Journal of Endocrinology cohort reported on effectiveness and safety in that population, and hypoglycemia is the consistent dose-limiting effect across the rhIGF-1 literature. Extrapolating from mecasermin to LR3 is not clean, because the entire point of LR3 is a higher free fraction at the same nominal dose. In practice LR3 is manufactured and sold as a cell culture reagent, a role where its potency and its lack of a human indication are both irrelevant.

The risks track directly from mechanism rather than from anecdote. IGF-1 receptor signaling drives proliferation and suppresses apoptosis, which is the anabolic effect and also the oncologic concern, so any active or historical malignancy is a hard stop. Cross-reactivity at the insulin receptor produces the hypoglycemia risk, which is why LR3 is dosed with food while GH secretagogues are dosed fasted. IGF-1 also promotes retinal neovascularization, making proliferative retinopathy a contraindication. It is prohibited in sport under WADA class S2, and current mass spectrometry methods for peptide analytes in the 2 to 10 kDa range cover compounds of exactly this size in doping control urine.

Common questions

IGF-1 LR3 Frequently Asked Questions

Two structural changes: arginine replaces glutamic acid at position 3, and a 13 amino acid extension is added to the N-terminus, taking the peptide from 70 to 83 residues. Both changes reduce binding to IGF binding proteins, which normally hold over 95 percent of circulating IGF-1 inactive. LR3 therefore acts at a much higher free fraction. It does not bind the IGF-1 receptor better than native IGF-1, it just arrives there in greater quantity.
Sources

Research & References

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 potencyPubMed · Journal of Molecular Endocrinology 1992Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated ratsPubMed · Biochemical Journal 1992Effects of interactions between IGFBPs and IGFs on the plasma clearance and in vivo biological activities of IGFs and IGF analogsPubMed · Growth Regulation 1993Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated ratsPubMed · Journal of Endocrinology 1992Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and AtrophyPubMed · Cells 2020Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndromePubMed · European Journal of Endocrinology 2021Chromatographic-mass spectrometric analysis of peptidic analytes (2-10 kDa) in doping control urine samplesPubMed · Journal of Mass Spectrometry 2024
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