What IGF-1 LR3 is and how it works
Insulin-like growth factor 1 (IGF-1) is a 70-amino-acid hormone, made mainly in the liver in response to growth hormone. It carries much of growth hormone's effect on growth: it binds the IGF-1 receptor, a tyrosine kinase closely related to the insulin receptor, and drives cell division, differentiation and survival. It also has insulin-like effects on glucose uptake.
IGF-1 LR3 changes two things. The glutamic acid at position 3 is replaced by arginine, which is the R3, and a 13-amino-acid extension is added to the N-terminus, which is the Long. The result runs to 83 residues and about 9.1 kDa, against roughly 7.6 kDa for native IGF-1. Both changes sharply reduce binding to the IGF-binding proteins while leaving the molecule able to activate the IGF-1 receptor. The variant came out of Australian work around 1990 on why certain forms of IGF-1, including a natural one missing the first three amino acids, were far more potent in cell culture; the answer was that they escaped the binding proteins.
That is why those proteins matter. In blood almost all IGF-1 is bound: six high-affinity binding proteins carry it, most of it in a large complex with IGFBP-3 and the acid-labile subunit. The complex keeps IGF-1 in the circulation for hours instead of minutes, controls how much reaches tissues and buffers its insulin-like effect on blood glucose. Cells in culture secrete binding proteins that blunt added IGF-1 in the same way. A variant that ignores them is more potent in a dish, and less predictable in an animal: more of it is free to act, and the usual buffer on free IGF-1 is largely absent.
What the research on IGF-1 LR3 shows
The best-established use is not in animals. IGF-1 LR3 is a routine supplement in serum-free cell culture, where it replaces or supplements insulin to support the growth and survival of cells such as the Chinese hamster ovary lines used to manufacture therapeutic proteins. Evidence level: cell culture and industrial practice.
Animal data date mainly from the early 1990s. In rats, IGF-1 variants with weak binding-protein affinity, the family LR3 belongs to, proved more anabolic than native IGF-1, including in rats made catabolic with dexamethasone, and produced marked growth of the gut. Those studies measured weight gain, nitrogen balance and organ weights over days to weeks; none was designed as a safety study.
There are no published controlled human trials of IGF-1 LR3 and no published human pharmacokinetic data, so half-life figures quoted online have no study behind them. What is known about IGF-1 in people comes from native IGF-1. Mecasermin, recombinant human IGF-1, is authorised in the EU as Increlex for children and adolescents with severe primary IGF-1 deficiency, and its trials and product information show what IGF-1 does in humans, including the risk of low blood sugar. That evidence does not transfer cleanly to a variant that escapes the binding proteins.
IGF-1 LR3 doses used in published research
| Setting | Material | Route and schedule | Main read-out |
|---|---|---|---|
| Cell culture, biomanufacturing | IGF-1 LR3 | Added to serum-free medium, in the nanogram-per-millilitre range | Cell growth, viability, protein yield |
| Rat catabolic and gut models | LR3 and related IGF-1 variants | Continuous subcutaneous infusion or injections over days | Weight gain, nitrogen balance, organ weights |
| Humans | IGF-1 LR3 | No published trials | – |
| Authorised medicine (comparison) | Mecasermin (native IGF-1, not LR3) | Twice-daily subcutaneous injection by body weight, with a meal or snack | Growth, blood glucose |
No human dose of IGF-1 LR3 has been validated and no medicine based on it exists. Mecasermin is in the table only to show how carefully native IGF-1 is handled where it is authorised: dosed by body weight, started low, given with food because of the hypoglycaemia risk. These are study and label designs, not instructions for use.
IGF-1 LR3 safety and side effects
No controlled safety data exist for IGF-1 LR3 in humans. The concerns below come from the biology of IGF-1 and from the authorised medicine.
- Hypoglycaemia. IGF-1 has insulin-like effects, and low blood sugar is a common adverse effect of mecasermin, which is why that medicine is given with food. A variant that escapes the binding proteins removes one of the usual buffers.
- Growth promotion. IGF-1 stimulates cell division and protects cells from apoptosis. Large observational studies link higher circulating IGF-1 with a modestly higher risk of some cancers, including prostate and breast cancer, and the EU product information for mecasermin rules it out where a tumour is present or suspected. For an unbuffered variant the concern is theoretical, not trivial.
- Tissue overgrowth. Acromegaly, the disease of long-term growth hormone and IGF-1 excess, shows what sustained overexposure does: enlargement of hands, feet, facial bones and internal organs.
- Feedback on the axis. IGF-1 suppresses the body's own growth hormone secretion, so giving it lowers GH output.
- Identity and folding. IGF-1 LR3 is a folded protein with three disulphide bonds, usually made recombinantly, and a correct mass does not prove correct folding. How it was produced and characterised matters more than for a short synthetic peptide.
Regulatory status of IGF-1 LR3 in Europe
IGF-1 LR3 is not authorised as a medicine in the EU or anywhere else; it is sold as a cell-culture reagent and as research material. The IGF-1 medicine authorised in the EU is mecasermin (Increlex), native human IGF-1, and that authorisation does not extend to variants. Rules on possession and import differ between member states.
In sport, IGF-1 and its analogues are prohibited at all times under S2 of the World Anti-Doping Agency Prohibited List, and IGF-1 LR3 falls in that group.
Sourcing IGF-1 LR3 and checking quality
King Peptides does not stock IGF-1 LR3. The closest product in its range is Tesamorelin 10 mg, and the difference needs spelling out. Tesamorelin is a GHRH analogue: it acts on the pituitary, which releases growth hormone, which in turn makes the liver produce more IGF-1, and IGF-1 levels did rise in the tesamorelin trials. The IGF-1 that results is the body's own, carried by the binding proteins and still under feedback control. That is a different mechanism one step up the axis, not a substitute compound, and it cannot answer a question about a variant that bypasses the binding proteins. The growth hormone axis group in our index lists the neighbours.
For tesamorelin, the certificate should show HPLC purity of at least 99%, a lot number matching the vial and a mass close to 5135.9 Da. For IGF-1 LR3 from any source, the mass should be close to 9.1 kDa. King Peptides supplies a lot-specific certificate with HPLC and mass spectrometry and dispatches from the Netherlands; delivery usually takes 1–2 business days within the Netherlands and 3–5 business days elsewhere in the EU by the shop's own estimate, with no customs inside the EU. Our guides cover reading a certificate of analysis and storage and reconstitution.
IGF-1 LR3: frequently asked questions
What do the Long and the R3 stand for? R3 marks the arginine that replaces glutamic acid at position 3; Long refers to the 13-amino-acid extension on the N-terminus, which brings the chain to 83 amino acids.
Is IGF-1 LR3 the same as mecasermin? No. Mecasermin is recombinant native human IGF-1, 70 amino acids, authorised in the EU as Increlex. IGF-1 LR3 is a modified variant with no approved medical use.
How does it differ from a growth hormone secretagogue? Secretagogues act at the top of the axis and raise the body's own growth hormone, and IGF-1 with it. IGF-1 LR3 acts at the bottom, directly on the IGF-1 receptor, so nothing about its level is set by the body. Our comparison of growth hormone secretagogues covers the upstream compounds.
Is IGF-1 LR3 banned in sport? Yes. IGF-1 and its analogues are prohibited at all times under S2 of the WADA Prohibited List.
Research use only. IGF-1 LR3 is described here for laboratory and scientific research. Research material carries no marketing authorisation, whatever the status of the molecule as a medicine elsewhere, and it is not intended for human or veterinary use. Nothing on this page is medical advice, and the dosing information above summarises published study designs. Always comply with the laws that apply in your country.