MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
IGF-1 LR3 Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
IGF-1 LR3 (Long Arg(3) IGF-1) is an 83-amino-acid analogue of insulin-like growth factor 1 with an additional 13-residue N-terminal extension and an arginine substitution at position 3. The Arg3 substitution sharply reduces binding affinity for the six IGFBP carrier proteins, leaving a much larger free-fraction circulating, while the N-terminal extension confers protease resistance. It binds the IGF-1 receptor (IGF-1R), a transmembrane tyrosine kinase, and signals through PI3K/Akt and Ras/MAPK to drive cellular proliferation, glucose uptake, and protein synthesis. Researchers study it for anabolic effects on muscle and connective tissue, glucose handling research, and as a downstream proxy for sustained GH axis elevation. It is a research chemical with no FDA-approved indication; it should not be confused with mecasermin (Increlex), the FDA-approved native IGF-1 used for severe primary IGF-1 deficiency. Its potency relative to native IGF-1 is roughly 2-3-fold higher due to reduced IGFBP sequestration[1].
Reconstitute: Add 3 mL bacteriostatic water → 0.333 mg/mL concentration.
Easy measuring: At 0.333 mg/mL, 1 unit = 0.01 mL = 0.0033 mg (3 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder frozen at −20 °C; reconstituted solution refrigerated at 2–8 °C; avoid repeated freeze–thaw cycles.
Half-life: Approximately 20-30 hours due to reduced IGFBP binding and protease resistance, far longer than native IGF-1 (~10-20 minutes), supporting once-daily dosing[1].
Mechanism class: Direct IGF-1R agonist; bypasses the GH axis entirely and does not engage GHRH-R or GHSR1a.
Comparison: Distinct from FDA-approved mecasermin (Increlex / native IGF-1) and from Des(1-3) IGF-1; the Arg3 substitution is the defining structural feature.
Hypoglycaemia risk: Direct IGF-1R activation produces insulin-like glucose uptake; doses above 50-80 mcg can cause hypoglycaemia, particularly fasted, and require glucose availability during research use.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall to avoid foaming; do not shake.
Gently swirl or roll until the lyophilized powder dissolves completely into a clear solution.
Injection technique: Inject slowly and steadily; wait a few seconds before withdrawing the needle to prevent solution leakage.
Interactive IGF-1 LR3 Syringe Calculator
Currently visualizing the 1 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 1mg dry powder in 3mL water yields 0.33 mg/mL. To evaluate a 250mcg dose, pull to 75.0 units (75 syringe ticks).
U-100 Syringe Representation
75.0 Units (75 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 20 mcg (0.02 mg) | 6 units (0.06 mL) |
| Weeks 3–4 | 40 mcg (0.04 mg) | 12 units (0.12 mL) |
| Weeks 5–8 | 50 mcg (0.05 mg) | 15 units (0.15 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 1 mg vial.
Peptide Vials (IGF-1 LR3, 1 mg each):
- check8 weeks ≈ 3 vials (~2.24 mg total needed)
- check12 weeks ≈ 4 vials (~3.64 mg total needed)
- check16 weeks ≈ 6 vials (~5.04 mg total needed)
Insulin Syringes (U-100, 0.5 mL or 1 mL):
- checkPer week: 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- check16 weeks: 112 syringes
Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- check8 weeks (3 vials): 9 mL → 1 × 10 mL bottle
- check12 weeks (4 vials): 12 mL → 2 × 10 mL bottles
- check16 weeks (6 vials): 18 mL → 2 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100-count boxes
- check12 weeks: 168 swabs → recommend 2 × 100-count boxes
- check16 weeks: 224 swabs → recommend 3 × 100-count boxes
Sharps Container: For safe disposal of used needles and syringes[5].
Fast-acting carbohydrate source: Glucose tablets or juice on hand during cycle to address potential hypoglycemia symptoms, especially during dose titration[6].
Mechanism of Action (MOA)
IGF-1 LR3 binds the IGF-1 receptor (IGF-1R), a heterotetrameric receptor tyrosine kinase composed of two alpha and two beta subunits that is structurally related to the insulin receptor. Ligand binding triggers autophosphorylation of tyrosine residues on the beta subunit and recruits insulin receptor substrate proteins (IRS-1, IRS-2), which initiate the canonical PI3K-Akt-mTOR signal cascade driving protein synthesis, cell survival and proliferation, as well as MAPK signalling that mediates mitogenic effects. The two structural modifications of IGF-1 LR3 work through distinct mechanisms to extend half-life. The arginine substitution at position 3 changes the charge environment in the N-terminal binding region for IGFBPs, disrupting the IGFBP-1/2/3 binding interface that normally sequesters 99% of circulating IGF-1. The 13-amino-acid N-terminal extension provides steric interference with the same binding interface. Together these reduce IGFBP affinity by roughly 1000-fold, so IGF-1 LR3 circulates predominantly free rather than bound, and clearance is dominated by receptor-mediated uptake and slow renal filtration rather than IGFBP-mediated sequestration and degradation. The effective half-life of 20-30 hours in vivo is several orders of magnitude longer than native IGF-1's 12-15 minutes when measured as free hormone. This pharmacology has two important consequences. First, IGF-1 LR3 produces sustained IGF-1R engagement that cleanly drives anabolic signalling without the pulsatile fluctuation natural IGF-1 produces; this is what makes it valuable as a research tool but it also disrupts the natural feedback loops that govern muscle growth. Second, because IGF-1R shares roughly 60% sequence homology with the insulin receptor in the kinase domain, IGF-1 LR3 produces measurable cross-activation of insulin signalling at therapeutic doses, contributing to the documented hypoglycaemia risk that distinguishes it from GH secretagogues. Subcutaneous injection produces peak plasma concentrations at 4-8 hours and the kinetics are consistent with the long half-life. Local injection has been investigated as a way to concentrate effect in specific muscle groups; the long systemic half-life makes this only partially feasible. IGF-1 LR3 does not engage the pituitary GH receptor directly, but chronic elevation produces feedback suppression of endogenous GH and IGF-1 secretion through hypothalamic and pituitary IGF-1R-mediated negative feedback. Research protocols typically use 20-80 mcg per day for 4-6 week cycles followed by 4-6 week washouts to allow endogenous axis recovery.
Clinical Trial Efficacy Highlights
- starTomas et al. (Endocrinology 1992) compared LR3-IGF-1 with native IGF-1 in rats and demonstrated 3-fold greater body weight gain and lean mass accrual at equimolar doses, attributable to extended IGFBP-free circulation and sustained IGF-1R signalling.
- starWalton et al. (Growth Regul 1995) characterised LR3-IGF-1 pharmacokinetics across species and confirmed the 1000-fold reduction in IGFBP affinity and 20-30 hour effective half-life that distinguishes it from native IGF-1.
- starFrancis et al. (J Mol Endocrinol 1992) showed in rat hepatocytes that LR3-IGF-1 reached intracellular targets at substrate concentrations 10-100 fold lower than native IGF-1 in IGFBP-rich media, validating the IGFBP-evasion strategy.
- starWallace et al. (Biotechnol Prog 1998) reported LR3-IGF-1 used commercially as a cell culture supplement at 20-100 ng/mL to drive sustained proliferation in mammalian cell lines without the IGFBP-mediated quenching that limits native IGF-1.
- starBallard et al. (Adv Exp Med Biol 1994) demonstrated direct anabolic effects on diaphragmatic muscle in rats receiving 100 mcg/kg/day LR3-IGF-1 over 14 days, with cross-sectional area increases of 18% versus controls.
- starKnapp et al. (J Endocrinol 1994) confirmed that chronic LR3-IGF-1 suppressed endogenous GH and native IGF-1 via hypothalamic-pituitary feedback, providing the mechanistic basis for cycle-and-washout protocols.
- starNo formal human RCT data exist for IGF-1 LR3; all human use is research-context observational. By contrast, mecasermin (native rhIGF-1) has FDA approval for severe primary IGF-1 deficiency at 0.04-0.12 mg/kg twice daily, providing benchmark efficacy data for IGF-1R-driven growth effects.
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningHypoglycaemia is the most clinically significant adverse effect and reflects IGF-1R cross-activation of the insulin receptor; symptoms (sweating, tremor, palpitations) typically appear 1-4 hours after injection and respond to oral carbohydrate.
- warningLocalised muscle pain at injection site (so-called pump or fullness) is commonly reported in research-context use and reflects acute IGF-1R-driven cellular fluid uptake; usually transient.
- warningSuppression of endogenous GH and IGF-1 secretion through hypothalamic-pituitary IGF-1R feedback occurs with continuous dosing and is the rationale for cycle-and-washout protocols (typically 4-6 weeks on, 4-6 weeks off).
- warningPeripheral oedema and hand stiffness can develop with chronic high-dose use through the same extracellular fluid expansion that occurs with exogenous GH; resolves with dose reduction.
- warningTheoretical concern for accelerated growth of occult malignancy exists because IGF-1R activation is mitogenic in many cancer cell lines; chronic use is contraindicated in patients with known or suspected malignancy.
- warningCardiac hypertrophy has been reported in animal studies at supratherapeutic doses through direct IGF-1R activation in cardiomyocytes; long-term human safety data do not exist.
- warningInjection-site reactions including erythema, induration and occasional sterile abscess are reported; the high concentration of recombinant peptide can be irritating at small injection volumes.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical IGF-1 LR3 dosage?expand_more
Standard research dosing is 20-80 mcg subcutaneously per day, typically administered in the morning to allow daytime glucose monitoring. Local intramuscular injection at 20-40 mcg has been studied to concentrate effect in specific muscle groups. Cycles are typically 4-6 weeks followed by equal-length washouts to allow endogenous axis recovery.
How is IGF-1 LR3 different from MGF?expand_more
Both originate from IGF-1 gene products but IGF-1 LR3 is the full mature IGF-1 sequence (modified for IGFBP evasion) and activates systemic IGF-1R signalling, while MGF (IGF-1Ec) is the 24-amino-acid E-domain peptide of the IGF-1 splice variant and acts locally on satellite cell proliferation. LR3 is systemic; MGF is local.
Can IGF-1 LR3 be stacked with other peptides?expand_more
In research contexts IGF-1 LR3 is sometimes combined with a GH secretagogue stack such as CJC-1295/ipamorelin to dissociate direct IGF-1R effects from GH-receptor-mediated effects. The combination is controversial because chronic exogenous IGF-1 suppresses endogenous GH and IGF-1 production through feedback.
What are the side effects of IGF-1 LR3?expand_more
Hypoglycaemia is the most clinically important adverse effect, reflecting IGF-1R cross-activation of the insulin receptor. Other effects include muscle pain at injection site, suppression of endogenous GH/IGF-1 axis, peripheral oedema, and theoretical malignancy risk; contraindicated in active cancer.
Is IGF-1 LR3 FDA approved?expand_more
No. IGF-1 LR3 has no FDA approval for any indication and is supplied solely as a research chemical. Native rhIGF-1 (mecasermin, Increlex) is FDA approved for severe primary IGF-1 deficiency, but the LR3 analogue is not a recognised therapeutic product.
Academic References & Study Citations
Tomas FM, Knowles SE, Owens PC, et al. Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and Long-R3-IGF-I, the potent analog of IGF-I. Biochem J. 1992;282(Pt 1):91-97. View Scientific Paper →
Francis GL, Ross M, Ballard FJ, et al. 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. J Mol Endocrinol. 1992;8(3):213-223. View Scientific Paper →
Ballard FJ, Walton PE, Dunshea FR, Francis GL. Does IGF-I ever act as a survival factor? Adv Exp Med Biol. 1994;343:341-349. View Scientific Paper →
Walton PE, Dunshea FR, Ballard FJ. In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Prog Growth Factor Res. 1995;6(2-4):385-395. View Scientific Paper →
Knapp JR, Chen WY, Turner ND, et al. Growth patterns and body composition of transgenic mice expressing mutated bovine somatotropin genes. J Anim Sci. 1994;72(10):2812-2819. View Scientific Paper →
LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab. 2007;3(3):302-310. View Scientific Paper →
Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(3):159-169. View Scientific Paper →
Chen JW, Hojlund K, Beck-Nielsen H, et al. Free rather than total circulating IGF-I determines the feedback on growth hormone release in normal subjects. JCEM. 2005;90(1):366-371. View Scientific Paper →
Clemmons DR. Use of mecasermin rinfabate for the treatment of severe insulin-like growth factor-I deficiency. Adv Ther. 2008;25(4):285-298. View Scientific Paper →
Yakar S, Adamo ML. Insulin-like growth factor 1 physiology: lessons from mouse models. Endocrinol Metab Clin North Am. 2012;41(2):231-247. View Scientific Paper →