IGF-1 LR3 (Long R3 IGF-1)
IGF-1 LR3 — hyperplasia, what the evidence really shows & status

Class: protein
Synonyms: IGF-1 LR3
Long R3 IGF-1
Long Arg3 IGF-1
LR3-IGF-1
a synthetic analog of Insulin-like Growth Factor 1. INCI: none
Function tags: muscle / anabolic (research)
cell-culture growth factor (its actual established use)
Overall evidence grade: D
WADA prohibited: yes
WADA note: Sport: WADA-prohibited at all times — Section S2 (Peptide Hormones, Growth Factors); validated LongR3-IGF-I detection assays exist (Mongongu 2020). Banned in and out of competition.
Last updated: 2026-07-13

In brief: IGF-1 LR3 is a long-acting engineered version of IGF-1, prized in the muscle community for one genuinely special property — hyperplasia, the formation of new muscle fibres via satellite cells, which steroids cannot do. But the honest reality is stark: it was created as a cell-culture reagent, no human trial has ever tested it for muscle or anything else, the hyperplasia effect in humans is debated, and its safety profile — hypoglycemia, tumour-promotion risk, organ overgrowth — is serious. Thrilling mechanism; unproven and genuinely risky product. Banned in sport.

## Identity an **83-amino-acid** engineered analog of IGF-1 (native IGF-1 is 70 aa; ~9 kDa) with two changes — an **arginine for glutamic acid at position 3** ("R3") and a **13-amino-acid N-terminal extension** ("Long"). Together these cut its binding to IGF-binding proteins (IGFBPs) by ~100–1000×. Since ~98–99% of native IGF-1 is normally sequestered by IGFBPs (half-life ~10–20 min), evading them makes LR3 far more potent and long-lasting — **half-life ~20–30 hours.** At **83 aa it is a protein**, above the "peptide" range, with **three disulfide bonds** — which is exactly why gray-market "IGF-1 LR3" is hard to fold, verify and trust. ## Mechanism (as proposed) IGF-1 LR3 binds the **IGF-1 receptor** (a receptor tyrosine kinase) → **PI3K/Akt/mTOR** (protein synthesis, survival, glucose uptake) and **MAPK/ERK** (proliferation) → in muscle, **satellite-cell activation** and new myonuclei/fibres. It also cross-reacts with the **insulin receptor** (lower affinity) → the **hypoglycemia** risk. The LR3 modifications let it slip past IGFBPs, so it stays free and active far longer than native IGF-1 — the same property that makes it potent is what makes its off-target and oncogenic risks harder to contain.

Evidence grades by outcome:
outcome: Muscle hypertrophy + hyperplasia via IGF-1R (the biology)
base: Cell culture + animal models
effect: Anabolic; satellite-cell activation; new fibres
caveat: The biology, in a dish and in animals — not injected LR3 in humans
outcome: IGF-1 LR3 for muscle building in humans (the marketed use)
grade: F
base: None
effect: Not demonstrated
caveat: Zero human trials for any endpoint; it's a cell-culture reagent
outcome: Hyperplasia in humans specifically
grade: D
base: Debated
effect: Uncertain
caveat: Established in vitro/animal; human extent at realistic doses is disputed
outcome: Native IGF-1 (mecasermin) — pediatric IGF-1 deficiency
base: FDA/EMA-approved
effect: Improves growth velocity
caveat: Native form, rare pediatric indication — not LR3, not muscle
outcome: Safety
base: Mecasermin record + IGF-1R pharmacology
effect: Serious concerns
caveat: Hypoglycemia (primary acute risk; with insulin → hospitalisations reported); tumour promotion — LR3 is engineered to evade the IGFBP system that normally reins IGF-1 in, an unstudied long-term oncogenic concern; acromegaly-like organ growth; insulin resistance; gray-market misfolding/endotoxin; WADA-banned

Legal status:
region: INT
status: See note
note: - Everywhere — not approved for muscle, performance or anti-aging. Native IGF-1 (mecasermin / Increlex) is FDA- and EMA-approved for pediatric severe primary IGF-1 deficiency only; IGF-1 LR3 is not separately authorised for anything therapeutic — it is a research / cell-culture reagent sold gray-market for bodybuilding.
- ⚠ Sport: WADA-prohibited at all times — Section S2 (Peptide Hormones, Growth Factors); validated LongR3-IGF-I detection assays exist. Banned in and out of competition.

Cosmetic claims:

Note: Reference entry — not sold here. The muscle world's hyperplasia dream — building new muscle fibres, not just bigger ones — and the honest reality behind it. Three things up front: it's a protein, not a peptide; there are zero human trials of it for muscle; and the safety profile is genuinely serious. No dosing published here.
Honest note: the hyperplasia idea is real and genuinely exciting — but it's proven in a Petri dish and lab animals, and the exact molecule you'd buy was designed to grow cells in that dish, not muscle in you. Zero human trials, a hypoglycemia risk that has put people in hospital, and — because it's built to evade the very system that normally keeps IGF-1 in check — a cancer concern that is essentially unstudied over the long term. Respect the mechanism; don't trust the vial.

Sources:
Chernausek SD, et al. (Mecasermin long-term treatment in severe primary IGF-1 deficiency — efficacy and adverse-effect profile: hypoglycemia, tonsillar hypertrophy, intracranial hypertension.) 2007.
Conlon MA, Tomas FM, et al. Long R3 IGF-I infusion stimulates organ growth… in the guinea pig. J Endocrinol. 1995.
Voorhamme D, Bhatt RR. LongR3-IGF-I as a more potent alternative to insulin in serum-free cell culture. Mol Biotechnol. (its actual use.)
Mongongu C, et al. (Validated detection assay for LongR3-IGF-I / R3-IGF-I in athlete samples.) 2020.