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Long R3 Insulin-like Growth Factor-1 (LR3 IGF-1)
A grey-market injectable 'research peptide' with NO human efficacy trials of the analog itself — the muscle-growth marketing is extrapolated from cell-culture and animal work. IGF-1 LR3 (Long R3 IGF-1) is a synthetic, engineered analog of human IGF-1: three residues are changed and a 13-amino-acid extension is added so it binds the IGF-1 receptor normally but barely binds the IGF-binding proteins that normally regulate native IGF-1. The result is a far longer-acting, less-regulated IGF-1 signal — which is exactly why bodybuilders inject it and exactly why it is concerning. It was created as a laboratory reagent (it drives cell proliferation in culture and organ/myoblast growth in fetal-sheep infusions), not as a medicine. There has never been a published human trial of IGF-1 LR3 for muscle, strength, or anything else. It is not an approved drug or a regulated supplement; it is an unregulated grey-market injectable. Activating the IGF-1 axis carries theoretical cancer-promotion risk (IGF-1 receptors are overexpressed on many tumors), and in animal infusions it suppressed insulin secretion and lowered blood glucose — a real hypoglycemia signal. It is described here to inform, not to recommend.
Research peptide — not a dietary supplement
IGF-1 LR3 is a research compound, not a regulated dietary supplement. It is typically administered by injection and sold “for research use only.” The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
Most IGF-1 LR3 studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality studies published 2003–2025.
Based on 8 studies
Confidence
Low confidenceBy outcome
Scored at the bottom of Emerging because there has never been a published human trial of the LR3 analog; all evidence is cell-culture and fetal-animal work, with real theoretical cancer and hypoglycemia risks and no quality-controlled product.
IGF-1 LR3 ('Long R3 IGF-1') is a synthetic analog of human insulin-like growth factor-1, engineered for the laboratory rather than the clinic. Two modifications define it: the glutamate at position 3 is replaced by arginine (the 'R3'), and a 13-amino-acid N-terminal extension is added (the 'Long').
Together these changes drastically reduce its affinity for the IGF-binding proteins (IGFBP-1 through -6) that normally sequester ~99% of circulating native IGF-1, while preserving high affinity for the IGF-1 receptor.
The practical consequence is a molecule that delivers a much more potent and far longer-lasting IGF-1-receptor signal than native IGF-1 at the same dose — which is precisely why it became a popular cell-culture reagent and, separately, a grey-market bodybuilding injectable.
IGF-1-receptor activation drives the PI3K/Akt/mTOR and ERK/MAPK pathways that promote cellular proliferation, protein synthesis, and survival.
In real experiments on the LR3 analog specifically, that signaling translates into: bioactive cell proliferation in recombinant-protein assays (Lu et al., 2023); proliferation of cultured bovine satellite cells (the muscle stem cells; Reiter et al., 2014) and fetal-sheep cardiomyocytes via ERK and PI3K (Sundgren et al., 2003); and, when infused into late-gestation fetal sheep, increased organ growth (heart, kidney, spleen, adrenals) and stimulated skeletal-myoblast proliferation (Stremming et al., 2022).
Here is the load-bearing caveat that must lead any honest reading: there has never been a published human trial of IGF-1 LR3 — not for muscle growth, strength, fat loss, recovery, or safety.
Every muscle/anabolic claim made for it is preclinical (cells and animals) or extrapolated from the biology of native IGF-1, and native IGF-1 is NOT the same molecule: it is regulated by binding proteins that the LR3 analog deliberately evades, so even the native-IGF-1 evidence base cannot be cleanly transferred.
The same fetal-sheep work that shows growth also shows the downside: a one-week IGF-1 LR3 infusion suppressed glucose-stimulated insulin secretion and lowered both insulin and glucose (White et al., 2021; 2023) — a concrete hypoglycemia mechanism.
And the IGF-1 axis itself is a recognized cancer-relevant pathway: IGF-1 receptors are overexpressed on many tumor types, which is why LR3-IGF-1 has been used as a tumor-targeting vehicle in oncology research (McTavish et al., 2009).
Chronically amplifying an unregulated IGF-1 signal therefore carries a theoretical risk of promoting growth of existing or nascent tumors, plus acromegalic/organ-overgrowth concerns inherent to any strong growth-factor agonist.
On top of the pharmacology, IGF-1 LR3 is an unapproved, unregulated grey-market injectable: identity, purity, dose, and sterility are not guaranteed, and injecting non-sterile peptide material carries infection and contamination risk independent of the molecule.
The evidence here is scored well below 3 and flagged Emerging: a genuine, interesting preclinical signal for cell and organ growth, with zero human data, real metabolic and oncologic theoretical risks, and no legitimate or quality-controlled product — sandboxed out of all goal- and stack-based recommendations.
IGF-1 LR3 carries an Arg-for-Glu substitution at position 3 plus a 13-residue N-terminal extension. These changes sharply reduce binding to the IGF-binding proteins (IGFBPs) that normally regulate native IGF-1, while keeping high affinity for the IGF-1 receptor — producing a more potent, longer-lasting IGF-1 signal. Demonstrated as 'low affinity for IGF binding proteins and high affinity for the IGF-1 receptor' in animal/cell work (White et al., 2021); never characterized in a human trial.
Binding the IGF-1 receptor activates the PI3K/Akt/mTOR and ERK/MAPK cascades that drive protein synthesis, cell proliferation, and survival. In cultured fetal-sheep cardiomyocytes, LR3 IGF-1-stimulated proliferation required both ERK and PI3K signaling (Sundgren et al., 2003). Established in cells/animals only.
LR3-IGF-1 stimulates proliferation of cultured muscle satellite cells (Reiter et al., 2014), and fetal-sheep LR3 IGF-1 infusion stimulated skeletal-myoblast proliferation in vivo (Stremming et al., 2022). This is the proposed route to muscle growth — demonstrated in cells and fetal animals, never in adult humans.
A one-week IGF-1 LR3 infusion into fetal sheep lowered plasma insulin and glucose and suppressed glucose-stimulated insulin secretion (White et al., 2021) — a concrete mechanism for the hypoglycemia risk reported anecdotally with grey-market use. Animal data only.
How IGF-1 LR3 works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — there are no human trials of the analog and no quality-controlled product. Preclinical cell/animal growth signals do not justify human self-injection.
Avoid — IGF-1-axis activation is a recognized theoretical tumor-promotion risk.
Avoid — IGF-1 LR3 suppressed insulin and lowered glucose in animals; hypoglycemia risk is real and could compound glucose-lowering medications.
Avoid entirely — a potent growth-factor agonist, completely unstudied in human pregnancy.
IGF-1 LR3 cross-talks with the insulin axis and lowered insulin/glucose in animal infusions. Combining it with insulin, sulfonylureas, or other hypoglycemic agents could compound blood-sugar lowering and precipitate hypoglycemia. No human interaction data exist.
Stacking with growth hormone or other growth-promoting agents would further amplify IGF-1-axis signaling and the associated organ-overgrowth and cancer-promotion concerns. Never studied in humans.
There are no human drug-interaction data for IGF-1 LR3 of any kind; interactions cannot be reliably predicted.
Tip: IGF-1 LR3 lowered insulin and glucose in animal infusions, and IGF-1-receptor activation has insulin-like effects. Hypoglycemia is a plausible and potentially dangerous effect; human frequency is unknown because no human has been studied.
Tip: IGF-1 receptors are overexpressed on many cancers; chronically amplifying an unregulated IGF-1 signal is a recognized theoretical cancer-promotion concern. Never quantified in human LR3 users.
Tip: Animal LR3 infusion increased visceral-organ growth; strong sustained IGF-1 agonism raises acromegalic/organ-overgrowth concerns. Unstudied in humans.
Tip: Grey-market injectable material has no identity/purity/sterility guarantees; reconstituting and injecting it carries contamination and infection risk independent of the molecule.
Tip: No human has ever been studied on IGF-1 LR3 — the side-effect profile in people is genuinely unknown. This is itself the warning.
The current evidence for IGF-1 LR3 is insufficient to assign an evidence score, based on 8 indexed studies. A grey-market injectable 'research peptide' with NO human efficacy trials of the analog itself — the muscle-growth marketing is extrapolated from cell-culture and animal work. IGF-1 LR3 (Long R3 IGF-1) is a synthetic, engineered analog of human IGF-1: three residues are changed and a 13-amino-acid extension is added so it binds the IGF-1 receptor normally but barely binds the IGF-binding proteins that normally regulate native IGF-1. The result is a far longer-acting, less-regulated IGF-1 signal — which is exactly why bodybuilders inject it and exactly why it is concerning. It was created as a laboratory reagent (it drives cell proliferation in culture and organ/myoblast growth in fetal-sheep infusions), not as a medicine. There has never been a published human trial of IGF-1 LR3 for muscle, strength, or anything else. It is not an approved drug or a regulated supplement; it is an unregulated grey-market injectable. Activating the IGF-1 axis carries theoretical cancer-promotion risk (IGF-1 receptors are overexpressed on many tumors), and in animal infusions it suppressed insulin secretion and lowered blood glucose — a real hypoglycemia signal. It is described here to inform, not to recommend. Representative study: PMID 36091374.
Dosing for IGF-1 LR3: No self-directed dose is recommended by SupStack. IGF-1 LR3 is an unapproved grey-market research chemical with no human dosing data and no quality control. We do NOT provide a dosing protocol. There has never been a human trial to establish a safe or effective dose; the only published dosing is in animals (e.g., fetal-sheep infusions) and does not translate to a human regimen.
Timing is flexible for IGF-1 LR3 — consistent daily use matters more than the time of day. There is no validated human dosing schedule because the analog has never been tested in humans.
No consumer dose of IGF-1 LR3 is endorsed, so there is no dose at which it can be called safe. Talk to a healthcare provider before taking it. Reported side effects include hypoglycemia (low blood sugar), tumour-promotion uncertainty, organ / acromegalic overgrowth. How often they occur is not established for all of them. Use caution if any of these apply to you: Not an approved medicine and not a regulated dietary supplement — unapproved grey-market injectable research chemical; do not self-source; No human safety data of the LR3 analog exists — every safety conclusion would be an extrapolation from cells, animals, or native IGF-1; Any personal or family history of cancer — IGF-1-axis activation is a theoretical tumor-promotion risk.
Mecasermin (IGF-1)
Too few graded studiesThe pharmaceutical-grade version of IGF-1 — an FDA/EMA-approved prescription injectable, but approved ONLY for a rare childhood growth disorder (severe primary IGF-1 deficiency / Laron syndrome), where it genuinely raises height velocity in clinical trials. It is the regulated counterpart to the grey-market igf-1-lr3 peptide bodybuilders inject, and shares the same core risks. Crucially, there is NO trial supporting its off-label use for muscle, performance, or anti-aging in healthy adults — and IGF-1's documented harms (hypoglycemia, intracranial hypertension, lymphoid/tonsillar hypertrophy, and a cancer concern because IGF-1 is mitogenic) are real. Not a dietary supplement, not a longevity drug.
Insulin (bodybuilding use)
Too few graded studiesInsulin is a life-saving prescription hormone for diabetes — and, used illicitly by bodybuilders as an off-label 'anabolic,' one of the most dangerous performance drugs in existence. The theory is nutrient partitioning: insulin drives glucose and amino acids into muscle and suppresses muscle-protein breakdown. But there is NO controlled evidence that insulin builds muscle or improves performance in healthy, non-diabetic athletes — and a non-diabetic who injects it risks profound, sometimes FATAL hypoglycemia (coma, seizures, brain injury, death), plus fat gain. This is a harm-reduction reference documenting a popular, deadly misuse, NOT a recommendation and NOT a dietary supplement.
ACE-031
Mostly mechanism / observationalAn investigational myostatin/activin 'trap' whose only human trial in patients was STOPPED for safety. ACE-031 is a fusion protein of the activin receptor type IIB (ActRIIB) extracellular domain and an IgG1-Fc, engineered by Acceleron Pharma to soak up myostatin and related ligands and thereby release the brake on muscle growth. It has real human data — a single-dose study in healthy postmenopausal women showed a genuine ~3% gain in lean mass — but its phase 2 trial in boys with Duchenne muscular dystrophy was HALTED after the second dosing regimen because of bleeding-related safety signals (nosebleeds/epistaxis and telangiectasias, dilated surface blood vessels). It is NOT an approved drug, development was discontinued, and anything sold grey-market under this name is unregulated. It is described here to inform, not to recommend.
CJC-1295
Mostly mechanism / observationalA synthetic long-acting analog of growth-hormone-releasing hormone (GHRH), promoted online to raise GH and IGF-1 for muscle, fat loss and 'anti-aging'. Honest appraisal: the only real human data are two small early-phase pharmacokinetic / safety studies from ~2006 that showed it raises GH and IGF-1 for days — they were never followed by efficacy trials in muscle, body composition or aging. There are NO human outcome RCTs. It is not a dietary supplement: it is sold 'for research use only', is injectable, and is banned by WADA. The original DAC version's clinical development was abandoned.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 8 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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