IGF-1 LR3 (Long R3 IGF-1, also written LR3IGF-I or LongR3-IGF-I) is a synthetic, lab-made variant of human insulin-like growth factor 1 (IGF-1). Australian researchers designed it in the early 1990s so that it would bind poorly to the IGF binding proteins that normally hold IGF-1 in check. In cell culture and in rats, this made it several times more potent than natural IGF-1.
IGF-1 LR3 has never been approved as a medicine anywhere, and a 2026 review found no peer-reviewed studies of it in humans (Dominikowski et al., Front Endocrinol 2026). Its legitimate use is as a growth-factor ingredient in cell-culture media. Everything known about its effects comes from cells, rats, pigs and monkeys. It is also prohibited in sport and has been found in black-market vials.
This page summarizes what laboratory and animal research and anti-doping labs report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Synthetic recombinant analogue of human IGF-1 |
| Approval | None; never approved for human use (FDA, EMA or elsewhere) |
| Legitimate use | Growth-factor supplement in cell-culture media |
| Key change vs IGF-1 | N-terminal extension plus arginine in place of glutamic acid at position 3 |
| Binding proteins | About 1000-fold lower affinity than IGF-1 for IGFBP-3 (lab studies) |
| Receptor binding | About 3-fold weaker than IGF-1 at the type 1 IGF receptor (lab studies) |
| Half-life | Not documented in humans; in rats it is cleared from blood faster than IGF-1 |
| Human studies | None published |
| WADA status | Prohibited at all times (S2.3, IGF-1 analogues) |
What it is
LR3 was developed by an Adelaide group (CSIRO and the Cooperative Research Centre for Tissue Growth and Repair) and described in 1992 (Francis et al., J Mol Endocrinol 1992). It is made in E. coli bacteria and differs from human IGF-1 in two ways:
| Change | What it does |
|---|---|
| N-terminal extension: the first 11 amino acids of methionyl porcine growth hormone, plus a two-amino-acid linker, added to the start of IGF-1 | Helps the molecule fold correctly during manufacture. On its own it also raised potency in cells that secrete binding proteins. This extension is the “Long” in the name. |
| Arg3 substitution: arginine replaces glutamic acid at position 3 of IGF-1 | Sharply reduces binding to IGF binding proteins. This is the “R3” in the name. |
The name refers to the extra length of the molecule, not to a long duration of action. Apart from position 3, the rest of the chain is the native 70-amino-acid IGF-1 sequence described on the IGF-1 page.
Why weaker binding makes it more potent
In the body, most IGF-1 is held by binding proteins, mainly IGFBP-3, which limit how much reaches its receptor. The Adelaide group showed that IGF-1 has roughly 1000-fold higher affinity than LR3 for IGFBP-3, IGFBP-4 and total rat plasma binding proteins (Ballard et al., Growth Regul 1993). Because more of it stays free, LR3 was 5–10 times more potent than IGF-1 in rat muscle cells (L6 myoblasts) that secrete binding proteins.
This potency depends on the binding proteins being present. In chicken embryo cells that secrete no detectable binding proteins, Long Arg3 IGF-1 was less potent than IGF-1 (Francis et al., J Mol Endocrinol 1992). In the same group’s measurements, LR3 bound the type 1 IGF receptor about 3-fold less well than IGF-1 (Tomas et al., Biochem J 1992). The same Adelaide group had earlier reached the same conclusion for Arg3-IGF-1 without the extension: its greater potency came from reduced binding-protein binding rather than stronger receptor binding (King et al., J Mol Endocrinol 1992).
Binding also varies by species. LR3 bound extremely weakly to rat plasma proteins but bound significantly in human, sheep, pig and chicken plasma (Lord et al., J Endocrinol 1994). Results from rats, where most of the potency data come from, may therefore overstate the difference in other species.
Related IGF-1 products
| Product | What it is | Status |
|---|---|---|
| IGF-1 (mecasermin, Increlex) | Recombinant IGF-1 identical to the human hormone | FDA-approved for severe primary IGF-1 deficiency in children |
| IGF-1 LR3 (this page) | Extended Arg3 analogue with weak binding-protein affinity | Not approved; research reagent |
| IGF-1 DES | IGF-1 missing its first three amino acids, also with weak binding-protein affinity | Not approved; research reagent |
| MGF and PEG-MGF | Peptides based on a splice variant of the IGF-1 gene | Not approved |
Pharmacokinetics
No human pharmacokinetic data have been published. The 2026 review lists its half-life in humans as not documented (Dominikowski et al., Front Endocrinol 2026).
Animal data contradict the popular idea that LR3 lasts longer in the blood than IGF-1. Because it does not ride on binding proteins, it is removed faster. In a tracer study in rats given intravenous doses, most LR3 circulated as free peptide and was broken down more quickly (Bastian et al., J Endocrinol 1993):
| Group (rats) | IGF-1 clearance, mL/min per kg | LR3 clearance, mL/min per kg |
|---|---|---|
| Virgin | 0.90 | 9.84 |
| Pregnant (low IGFBP-3) | 2.88 | 9.19 |
When pregnancy lowered binding proteins, IGF-1 clearance sped up toward that of LR3, while LR3 clearance barely changed. The authors concluded that binding-protein association explains the difference (Ballard et al., Growth Regul 1993).
Anti-doping studies in rats point the same way. After a single intramuscular dose of 100 µg/kg, unchanged LR3 disappeared from blood after 4 h, while a breakdown product missing the first 11 amino acids was detectable up to 16 h (Mongongu et al., Drug Test Anal 2021). The same breakdown products formed when LR3 was incubated in human whole blood.
Faster clearance does not mean shorter effects. In pigs, LR3 and other weak-binding variants lowered blood sugar 2–3 times more potently than IGF-1 and kept it suppressed far longer over 4 hours, even though they leave the blood faster (Tomas et al., J Endocrinol 1997).
Approved medical use
There is none. LR3 has never been approved for use in humans (Mongongu et al., Drug Test Anal 2021). The only approved IGF-1 drug is mecasermin, covered on the IGF-1 page.
Its established use is in biotechnology. LR3 is added to serum-free cell-culture media in place of insulin to keep cells growing. In one study of Chinese hamster ovary (CHO) cell lines making recombinant proteins, it sustained cell viability better than insulin (Morris & Schmid, Biotechnol Prog 2000).
What the research shows
All of the evidence below is from animals. No controlled human trial has tested LR3 for muscle, fat loss, recovery or any medical condition.
Growth and muscle protein in rats
In rats made catabolic (muscle-wasting) with the steroid dexamethasone, IGF-1 given by implanted pump for 7 days partly reversed weight loss, and LR3 and IGF-1 DES were each about 2.5 times more potent than IGF-1 (Tomas et al., Biochem J 1992). Both muscle protein synthesis and breakdown shifted in an anabolic direction. Carcass weight as a share of body weight stayed low in treated rats, although the carcass weight gained was protein rather than fat.
In normal growing female rats treated for 14 days, LR3 at 44 µg/day produced effects similar to IGF-1 at 278 µg/day: 18–26% increases in weight gain, nitrogen retention and feed efficiency (Tomas et al., J Endocrinol 1993). Body proportions stayed about the same, and the gain in nitrogen could not be explained by measured muscle protein turnover.
The gut grows most
The intestine was one of the most responsive tissues. In dexamethasone-treated rats, IGF-1 analogues were consistently several times more potent than IGF-1 at enlarging the stomach, small intestine and colon (Read et al., J Endocrinol 1992). In normal rats given LR3 at 278 µg/day for 14 days (Steeb et al., Am J Physiol 1994):
| Measure | Change with LR3 |
|---|---|
| Total gut weight | +43% |
| Small intestine weight | +47% |
| Small intestine length | +13% |
| Crypt cell population | +33% |
Pigs: growth was reduced, not increased
Pigs respond to GH and have high IGF-2 levels, so they are closer to humans in some respects than rats. In 55 kg finisher pigs, a 4-day infusion of LR3 at 180 µg/kg/day (Dunaiski et al., J Endocrinol 1997):
- reduced daily weight gain and food intake;
- lowered blood IGFBP-3, the pigs’ own IGF-1 and insulin;
- cut mean GH by 23% and the area under GH peaks by 60%.
Adding pig GH did not restore growth. A review of the pig program concluded that chronic LR3 reduced growth in older pigs, probably through feedback suppression of GH, whereas it increased growth in neonatal pigs that are not yet GH-responsive (Walton et al., Prog Growth Factor Res 1995). In artificially reared piglets, LR3 raised daily weight gain from 386 to 457 g/day only in the second 9 days of infusion, and only when the piglets could feed freely (Dunshea et al., Br J Nutr 2002).
Other animal research
In a mouse model of Alzheimer’s disease, 7 months of intranasal LR3 improved body composition and some features of amyloid plaques but did not preserve memory or behavior (Engel et al., J Alzheimers Dis 2025).
Side effects and risks
No human safety data exist. The risks below come from animal studies and from what is known about IGF-1 itself.
Hypoglycemia
Like IGF-1, LR3 lowers blood sugar. In pigs it was 2–3 times more potent than IGF-1 at reaching the low point, and the weak-binding variants produced roughly 4- to 8-fold more cumulative glucose lowering over 4 hours (Tomas et al., J Endocrinol 1997). In children treated with approved IGF-1, hypoglycemia is the most common serious side effect (see the IGF-1 page).
Suppression of the body’s own GH and IGF-1
In pigs, LR3 lowered the animals’ own IGF-1, IGFBP-3, insulin and GH (Dunaiski et al., J Endocrinol 1997). Whether this happens in humans is unknown.
Growth of non-muscle tissue and cancer concern
In rats, the gut was one of the most sensitive tissues to IGF-1 and its analogues, which enlarged it more potently than IGF-1 (Read et al., J Endocrinol 1992). IGF-1 stimulates cell division, the approved IGF-1 drug is contraindicated in people with cancer, and higher natural IGF-1 levels are modestly associated with some cancers (see the IGF-1 page). The 2026 review describes the mitogenic (cell-proliferation) risk of LR3 as theoretical, because it has not been studied in humans (Dominikowski et al., Front Endocrinol 2026).
Product quality
Because LR3 is not a medicine, products sold outside research supply are unregulated. Anti-doping labs have found:
- unpurified LR3 among confiscated black-market products in 2009 (Kohler et al., Drug Test Anal 2010);
- an injection vial containing a His-tagged form of LR3, a purification tag used in lab production, whose effects in humans are unknown (Kohler et al., Growth Horm IGF Res 2010);
- frequent oxidized, lower-quality peptide forms in black-market products (Mongongu et al., Drug Test Anal 2021).
Legal status and use outside medicine
LR3 is not an approved drug in the US or EU. It is not named among the anabolic steroids in the US Schedule III list (21 CFR 1308.13).
The WADA 2026 Prohibited List bans “IGF-1, mecasermin and its analogues” at all times under S2.3 (growth factors), which covers LR3. Anti-doping researchers note that LR3 is readily available on the black market for bodybuilding (Mongongu et al., Drug Test Anal 2021). Labs can detect it in plasma at low ng/mL levels despite the large excess of natural IGF-1, and a breakdown product roughly doubled the detection window in rats (Thomas et al., Growth Horm IGF Res 2017).
Key takeaways
- Never tested in people. IGF-1 LR3 is a research reagent with no approval and no published human studies.
- Potent because it escapes binding proteins. It binds IGFBP-3 about 1000-fold less than IGF-1 and was 2.5–6 times more potent in rats, despite weaker receptor binding.
- “Long” does not mean long-lasting. In rats it was cleared from blood much faster than IGF-1; its human half-life is undocumented.
- Animal results conflict. It increased weight and gut growth in rats but reduced growth and suppressed GH in older pigs.
- Strong blood-sugar effect. In pigs it lowered glucose more potently and for longer than IGF-1.
- Banned and unregulated. WADA prohibits it at all times, and black-market samples have contained impure, oxidized or lab-tagged forms.
Sources
- 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. PubMed.
- King R, Wells JR, Krieg P, et al. Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. J Mol Endocrinol. 1992;8(1):29–41. PubMed.
- Ballard FJ, Walton PE, Bastian S, et al. Effects of interactions between IGFBPs and IGFs on the plasma clearance and in vivo biological activities of IGFs and IGF analogs. Growth Regul. 1993;3(1):40–44. PubMed.
- Tomas FM, Knowles SE, Owens PC, et al. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem J. 1992;282(Pt 1):91–97. PubMed.
- Tomas FM, Knowles SE, Chandler CS, 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):413–421. PubMed.
- Lord AP, Bastian SE, Read LC, Walton PE, Ballard FJ. Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I variants with rat, sheep, pig, human and chicken plasma-binding proteins. J Endocrinol. 1994;140(3):475–482. PubMed.
- Bastian SE, Walton PE, Wallace JC, Ballard FJ. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats. J Endocrinol. 1993;138(2):327–336. PubMed.
- Tomas FM, Walton PE, Dunshea FR, Ballard FJ. 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. J Endocrinol. 1997;155(2):377–386. PubMed.
- Read LC, Tomas FM, Howarth GS, et al. Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats. J Endocrinol. 1992;133(3):421–431. PubMed.
- Steeb CB, Trahair JF, Tomas FM, Read LC. Prolonged administration of IGF peptides enhances growth of gastrointestinal tissues in normal rats. Am J Physiol. 1994;266(6 Pt 1):G1090–G1098. PubMed.
- Dunaiski V, Dunshea FR, Walton PE, Goddard C. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. J Endocrinol. 1997;155(3):559–565. PubMed.
- 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. PubMed.
- Dunshea FR, Chung CS, Owens PC, Ballard JF, Walton PE. Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs. Br J Nutr. 2002;87(6):587–593. PubMed.
- Engel MG, Narayan S, Cui MH, 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. PubMed.
- Morris AE, Schmid J. Effects of insulin and LongR(3) on serum-free Chinese hamster ovary cell cultures expressing two recombinant proteins. Biotechnol Prog. 2000;16(5):693–697. PubMed.
- Dominikowski A, Rękoś Z, Olejarz M, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026;17:1822475. PubMed.
- Mongongu C, Coudoré F, Domergue V, 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. PubMed.
- Thomas A, Walpurgis K, Delahaut P, et al. Determination of LongR(3)-IGF-I, R(3)-IGF-I, Des1-3 IGF-I and their metabolites in human plasma samples by means of LC-MS. Growth Horm IGF Res. 2017;35:33–39. PubMed.
- Kohler M, Thomas A, Walpurgis K, et al. Detection of His-tagged Long-R³-IGF-I in a black market product. Growth Horm IGF Res. 2010;20(5):386–390. PubMed.
- Kohler M, Thomas A, Geyer H, et al. Confiscated black market products and nutritional supplements with non-approved ingredients analyzed in the Cologne Doping Control Laboratory 2009. Drug Test Anal. 2010;2(11-12):533–537. PubMed.
- World Anti-Doping Agency. 2026 Prohibited List. WADA 2026 Prohibited List.
- US Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.