IGF-1 LR3
IGF-1 with a 13-amino-acid extension and one swapped residue, so the proteins that normally hold IGF-1 in check barely touch it: potent in rats and calves, cleared quickly, and never given to a person in a published study
IGF-1 LR3 is an 83-amino-acid version of insulin-like growth factor 1, made in 1992 by adding 13 residues to the front of the hormone and replacing glutamate 3 with arginine. The changes leave it able to activate IGF-1 receptors while IGF-binding proteins, which hold most natural IGF-1 in an inactive reserve, barely bind it. In rats it was 1.5 to 2 times as potent as IGF-1 when infused and was cleared from the blood faster. It has been studied in rats, mice, guinea pigs, calves and fetal sheep. No published study has given it to a person.
What is it?
Most of the IGF-1 in blood is not free to act. It is held by a family of six IGF-binding proteins, which carry it, slow its clearance and ration how much reaches cells. In 1992 an Australian group built analogues designed to slip that control: the full IGF-1 chain, preceded by methionine, the first 11 amino acids of porcine growth hormone and valine-asparagine, with glutamate at position 3 of IGF-1 replaced by arginine. They called the result Long [Arg3]-IGF-I. In rat muscle cells it and its sister analogues were more potent than IGF-1 at stimulating protein and DNA synthesis and at slowing protein breakdown.
Animal studies followed. In growing female rats, 44 micrograms a day of the analogue matched the growth effect of 278 micrograms a day of IGF-1. Infused continuously, it was 1.5 to 2 times as potent as IGF-1 for weight gain and organ weights, and it kept some of that advantage when injected once a day, although it barely matched IGF-1 at reversing muscle loss in rats given dexamethasone. The same paper reports that because binding proteins do not hold it, the rat clears it from the circulation faster than IGF-1. After one intramuscular dose in rats, anti-doping chemists could no longer find the intact peptide after four hours.
What it does in whole animals is narrower than its reputation. Guinea pigs infused for a week grew larger guts, kidneys, spleens and adrenal glands without growing overall. In newborn calves, injections under the skin lowered blood glucose and insulin and suppressed the animals' own IGF-1 and growth hormone, while the same dose by mouth was not absorbed. In growth-restricted fetal sheep a week of infusion did not improve growth, and a 90-minute infusion into normal fetal sheep cut insulin during a glucose clamp by 66%. In mice with an Alzheimer's-like disease, seven months of nasal doses changed amyloid plaques but did not preserve memory or behaviour.
It is also a standard laboratory reagent, used because it acts without binding-protein interference, and a bodybuilding drug sold without approval. PubMed lists 127 records under its names, searched on September 27, 2026, and none describes giving it to a person; the one record indexed as a clinical trial was a randomized study in rats. Analyses of black-market products found oxidised, lower-quality peptide. Recombinant human IGF-1 itself, mecasermin, is an approved drug for severe primary IGF-1 deficiency; IGF-1 LR3 is a different molecule and is approved nowhere.
Mechanism of Action
IGF-1 LR3 acts on the same receptors as IGF-1. What is different is how little of it the binding proteins hold, which makes it more potent and also changes how long it lasts. Every pathway below comes from animal or laboratory studies.
Escaping the binding proteins
The N-terminal extension and the arginine at position 3 cut the analogue's affinity for IGF-binding proteins to very low levels while leaving receptor activity intact. More of each dose is free to reach receptors, which is why it outperformed IGF-1 in rat muscle cells and growing rats. The same property means the rat clears it faster than IGF-1, so its advantage shrank when it was injected rather than infused continuously.
IGF-1 receptor signalling
In lactating mice, injections raised phosphorylated Akt in the mammary gland, a marker of IGF-1 receptor signalling, and modestly increased milk production. In muscle cell cultures it stimulated proliferation, and a binding protein added back suppressed that effect through a route that did not depend on IGF at all.
Glucose and insulin
IGF-1 can act through the insulin receptor, and its analogues lower blood sugar. In newborn calves, 50 µg/kg a day under the skin lowered plasma glucose and insulin. In fetal sheep a 90-minute infusion cut insulin by 66% during a glucose clamp; islets taken out of those fetuses secreted insulin normally, suggesting the suppression is acute.
Organ growth rather than body growth
Guinea pigs infused for a week gained gut, kidney, spleen and adrenal weight but not body weight, while their natural IGF-1, IGF-II and binding proteins fell. Rat pups fed it grew taller intestinal villi, and rats given it absorbed a glucose tracer faster through a heavier gut lining. Calves given it showed no change in intestinal structure.
Published Research
PubMed lists 127 records under IGF-1 LR3's names, and none gives it to a person. The fifteen cards below are twelve animal studies and three laboratory studies that name it in their titles. Five papers that name it only in their abstracts, including the 1992 paper that first made it and the two rat studies that measured its potency, are in the References.
Bigger organs, not bigger guinea pigs
Female guinea pigs were infused for seven days with guinea pig IGF-I, IGF-II or 120 µg/day of long R3 IGF-I. None of the treatments changed body weight gain, feed intake, feed efficiency or carcass composition. Long R3 IGF-I did increase the relative weights of the adrenals, gut, kidneys and spleen, and plasma IGF-I, IGF-II and IGF-binding protein concentrations fell.
Where stomach enzymes cut it
Chemists measured how pepsin digests long-R3-IGF-I. It first cut the Leu10-Phe11 bond in the N-terminal extension, then four sites within the IGF-I part. Five single-point mutants all kept growth-promoting activity equal to or above IGF-I, and one, Phe16Ala, was markedly more resistant to pepsin, which the authors proposed for oral use in the gut.
Newborn calves: injected versus swallowed
Calves received 50 µg/kg a day of Long-R3-IGF-I for their first week, either under the skin or by mouth. Plasma Long-R3-IGF-I rose only after injection. Injection lowered the calves' own IGF-I and growth hormone concentrations without changing the pattern of growth hormone secretion, and raised IGF-binding protein-2.
Lower glucose and insulin in calves
In the same calf model, Long-R3-IGF-I injected under the skin at 50 µg/kg a day for seven days lowered plasma glucose and insulin, while the same dose given with milk had no effect. Growth hormone given for comparison transiently raised prolactin; neither treatment changed the other hormones and metabolites measured.
No change in the calf gut
Histology of the small intestine in these calves showed that prolonged colostrum feeding enlarged the villi, while Long-R3-IGF-I, injected or fed at 50 µg/kg a day for a week, had no significant effect on intestinal structure. High-dose growth hormone reduced villus size.
Taller villi in rat pups
Newborn rats reared artificially were fed milk replacer with or without long R3 IGF-I for three days. Pups fed the analogue had taller intestinal villi and more cells than pups on milk replacer alone, and more than mother-fed controls, pointing to a direct effect of milk-borne growth factors on the newborn gut.
Gut absorption in rats
Rats received IGF-I or long-R3-IGF-I from a pump under the skin for seven days. Only the analogue increased the early rate at which a glucose tracer reached the blood, by 40% at the lower tracer dose, and jejunal uptake per centimetre by up to 69%; the gain disappeared when expressed per gram of tissue, suggesting a thicker gut lining rather than more active glucose transport.
A binding protein that still slowed it
In L6 rat muscle cells, which make no IGFBP-3 of their own, added porcine IGFBP-3 suppressed proliferation driven by IGF-I and by Long-R3-IGF-I alike. Because the analogue barely binds IGFBP-3, the result shows the binding protein can slow cell growth through a route that does not involve capturing IGF.
Milk production in mice
Lactating mice were injected with mouse growth hormone, prolactin or long-R3-IGF-I. Growth hormone increased litter weight gain; long-R3-IGF-I raised mammary phospho-Akt and SOCS3 expression and had a modest effect on lactation capacity. Prolactin did not increase milk production.
What anti-doping chemists find
Researchers validated a test for IGF-I analogues in serum using antibody capture and high-resolution mass spectrometry, and found oxidised, lower-quality peptide in black-market products. After one intramuscular dose of 100 µg/kg in rats, intact LongR3-IGF-I disappeared after four hours, while two other analogues remained detectable for 24 hours; newly identified breakdown products could extend detection.
Insulin suppressed in fetal sheep
Late-gestation fetal sheep were infused with IGF-1 LR3 or a control for 90 minutes. Fetal insulin fell, and insulin during a hyperglycaemic clamp was 66% lower than in controls. Islets isolated right after the infusion secreted insulin normally in the dish, suggesting the suppression was acute rather than built into the cells.
Making it in yeast
Human IGF-1 and LR3 IGF-1 were produced in the yeast Pichia pastoris as fusions with a xylanase enzyme, reaching about 0.5 and 1 gram per litre of fusion protein in a 15-litre bioreactor. The purified peptides stimulated cell proliferation comparably to standard IGF-1.
Nasal doses in Alzheimer's mice
Male 5XFAD mice and normal mice (19 to 27 per group) received intranasal long R3 IGF-1 or a control for seven months. Treated 5XFAD mice had better body composition and fewer filamentous amyloid plaques, with less of the small amyloid oligomers, but their behaviour and memory were not preserved on any of several tests.
No help for growth-restricted fetuses
Growth-restricted fetal sheep received IGF-1 LR3 (1.17 µg/kg per hour) or vehicle for a week, seven per group. Fetal weight, insulin, glucose, oxygen and glucose-stimulated insulin secretion did not differ, but circulating amino acids fell with treatment. An earlier study by the group had found that a higher dose in normal fetuses increased body weight while lowering insulin.
A nerve conduit that releases it
In rats with a 1 cm gap in the sciatic nerve (five per group, six groups), a conduit made from decellularised plant stem and gel that slowly released IGF-1 LR3 improved axonal regeneration on gait, electrical and tissue measures, performing comparably to a nerve autograft without signs of systemic toxicity.
What people say, and what was measured
IGF-1 LR3 is an engineered IGF-1 that evades the binding proteins which normally hold IGF-1 in check. That is the selling point and the problem: the same modification that makes it potent is why its effects in animals are not confined to muscle.
It builds muscle far more powerfully than ordinary IGF-1.
Heard in: Grey Peptides listing review, October 1, 2026: listings sell it as the potent IGF-1 variant for lean mass. Sellers are not named.
Greater potency than IGF-1 is established, in rats: analogues that bind poorly to the binding proteins were superior when infused, and anabolic effects were shown in normal and catabolic rats. Those are the sources this claim comes from, and no human trial of muscle growth appears on this entry. PMID: 8708565, 8371075, 8919033
Shown in animals or cells onlyIt grows the tissue you train, because it acts locally.
Heard in: Grey Peptides listing review, October 1, 2026: listings describe local or site-specific growth. Sellers are not named.
The opposite is what was measured. Infused into rats it stimulated organ growth while reducing something else, and in fetal sheep it increased organ growth without stimulating nutrient uptake the way growth requires. In growth-restricted fetal sheep it did not promote growth at all, and it lowered circulating branched-chain amino acids. PMID: 7561636, 33427051, 39679943
Shown in animals or cells onlyIt is safe — it is just a form of a hormone you already make.
Heard in: Grey Peptides listing review, October 1, 2026: listings present it as a natural growth factor. Sellers are not named.
An acute infusion into fetal sheep cut insulin concentrations and left insulin secretion during a hyperglycaemic clamp 66% lower than control. That is a direct metabolic effect of the engineered molecule, measured, in an animal. There is no human safety study here. PMID: 37114757, 39679943
Shown in animals or cells onlyIt cannot be detected on a test.
Heard in: Grey Peptides listing review, October 1, 2026: listings suggest it is not covered by standard screens. Sellers are not named.
A method to detect LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I using immunopurification has been published, built for precisely this class of analogue. PMID: 33587816
Contradicted by the ruleEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
IGF-1 LR3 has no approved or studied human dose. The published doses come from animals, mostly given by continuous infusion, and are not transferable to people. The daily microgram amounts that circulate for injection are community figures with no trial behind them.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From animal studies; there are no human safety data.
Contraindications & Cautions
No trial defined who should avoid IGF-1 LR3. These cautions follow from how it acts and what animal studies found.
Legal Status
IGF-1 LR3 is not approved as a medicine anywhere. Status as of September 27, 2026.
Frequently Asked Questions
?What is the difference between IGF-1 LR3 and IGF-1?
IGF-1 LR3 is the full 70-amino-acid IGF-1 chain with 13 extra residues at the front (methionine, the first 11 amino acids of porcine growth hormone and valine-asparagine) and arginine in place of glutamate at position 3. Those changes almost stop IGF-binding proteins from holding it, while it still activates IGF-1 receptors. In rats it was 1.5 to 2 times as potent as IGF-1 when infused.
?Is IGF-1 LR3 longer-acting than IGF-1?
Not in the animal data. Binding proteins normally slow IGF-1's clearance, and because they barely hold LR3, rats cleared it from the circulation faster than IGF-1. After one intramuscular dose in rats, the intact peptide could not be found after four hours. Its extra potency comes from being free to act, not from lasting longer.
?Has IGF-1 LR3 been tested in humans?
No. PubMed lists 127 records under its names, and none describes giving it to a person; the one indexed as a clinical trial was a randomized study in rats. Everything known about its effects comes from rats, mice, guinea pigs, calves, fetal sheep and cell cultures.
?Can IGF-1 LR3 cause low blood sugar?
In animals it lowered glucose. Newborn calves injected with 50 µg/kg a day had lower plasma glucose and insulin, and a 90-minute infusion into fetal sheep cut insulin during a glucose clamp by 66%. No study has measured its effect on blood sugar in people.
?Does IGF-1 LR3 raise cancer risk?
It has not been studied in people, so no one knows. What is established is that IGF-1 signalling drives the growth of some cancer cells, and in culture long R3 IGF-I stimulated MCF-7 breast cancer cells as strongly as insulin. That is a reason for caution, not a measured risk.
?Can drug tests detect IGF-1 LR3?
Yes. Anti-doping laboratories have validated antibody-capture and mass-spectrometry tests for IGF-1 analogues in serum. The intact peptide disappeared within four hours of a dose in rats, but breakdown products identified in the same study can extend detection.
References
- [pubmed] Conlon MA, et al. "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." J Endocrinol, 1995;146(2):247-53. PMID: 7561636.
- [pubmed] Bryant KJ, et al. "Design and characterisation of long-R3-insulin-like growth factor-I muteins which show resistance to pepsin digestion." Growth Factors, 1996;13(3-4):261-72. PMID: 8919033.
- [pubmed] Hammon H, et al. "The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I." Am J Physiol, 1997;273(1 Pt 1):E130-8. PMID: 9252489.
- [pubmed] Hammon H, et al. "Endocrine and metabolic changes in neonatal calves in response to growth hormone and long-R3-insulin-like growth factor-I administration." Biol Neonate, 1998;73(2):121-8. PMID: 9483305.
- [pubmed] Bühler C, et al. "Small intestinal morphology in eight-day-old calves fed colostrum for different durations or only milk replacer and treated with long-R3-insulin-like growth factor I and growth hormone." J Anim Sci, 1998;76(3):758-65. PMID: 9535335.
- [pubmed] Staley MD, et al. "Rat milk and dietary long arginine3 insulin-like growth factor I promote intestinal growth of newborn rat pups." Pediatr Res, 1998;44(4):512-8. PMID: 9773839.
- [pubmed] Garnaut SM, et al. "Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut mucosal growth responses." Growth Factors, 2002;20(1):17-25. PMID: 11999215.
- [pubmed] Xi G, et al. "Effect of recombinant porcine IGFBP-3 on IGF-I and long-R3-IGF-I-stimulated proliferation and differentiation of L6 myogenic cells." J Cell Physiol, 2004;200(3):387-94. PMID: 15254966.
- [pubmed] Hadsell DL, et al. "Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression." J Endocrinol, 2008;198(1):61-70. PMID: 18577570.
- [pubmed] Mongongu C, et al. "Detection of LongR(3) -IGF-I, Des(1-3)-IGF-I, and R(3) -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes." Drug Test Anal, 2021;13(7):1256-1269. PMID: 33587816.
- [pubmed] White A, et al. "Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets." J Dev Orig Health Dis, 2023;14(3):353-361. PMID: 37114757.
- [pubmed] Lu Z, et al. "Recombinant expression of IGF-1 and LR3 IGF-1 fused with xylanase in Pichia pastoris." Appl Microbiol Biotechnol, 2023;107(14):4543-4551. PMID: 37261455.
- [pubmed] Engel MG, et al. "Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice." J Alzheimers Dis, 2025;103(1):113-126. PMID: 39610283.
- [pubmed] White A, et al. "IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep." Am J Physiol Endocrinol Metab, 2025;328(1):E116-E125. PMID: 39679943.
- [pubmed] Yavuz E, et al. "Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration." Int J Biol Macromol, 2025;329(Pt 2):147888. PMID: 41015370.
- [pubmed] Francis GL, 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):213-23. PMID: 1378742.
- [pubmed] Tomas FM, et al. "Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats." J Endocrinol, 1993;137(3):413-21. PMID: 8371075.
- [pubmed] Tomas FM, et al. "Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection." J Endocrinol, 1996;150(1):77-84. PMID: 8708565.
- [pubmed] Stremming J, et al. "IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus." Am J Physiol Endocrinol Metab, 2021;320(3):E527-E538. PMID: 33427051.
- [pubmed] Vink-van Wijngaarden T, et al. "Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089." Eur J Cancer, 1996;32A(5):842-8. PMID: 9081364.
- [fda-pi] Increlex (mecasermin [rDNA origin]) Prescribing Information. Ipsen Biopharmaceuticals. (Reference: native IGF-1, not LR3.)
Sources & Citations
Every citation on this page is PubMed-indexed and has been checked against its record, except the Increlex prescribing information, cited for mecasermin. Our earlier entry cited two papers that did not exist as written: its Francis 1992 title matches no PubMed record, and its journal pages belong to the Long [Arg3]-IGF-I paper now cited; its Tomas title belongs to a 1996 paper while its pages belong to a 1993 one, and both are now cited. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.