IGF-1 LR3
Long R3 Insulin-like Growth Factor-1 · Long R3 IGF-1 · LR3 IGF-1 · IGF-I LR3 · Long R3 IGF-I
Modified IGF-1 that evades its binding proteins, making it far more potent than the native hormone.
Typical dose
40 mcg
Once daily
Range
20–80
mcg
Half-life
—
see Dosing
Evidence
Animal only
Subcutaneous · Intramuscular
What it is
IGF-1 LR3 is an engineered version of insulin-like growth factor 1, the hormone that carries out most of what growth hormone gets credited with. Two changes were made to it: arginine replaces glutamic acid at position three, and a thirteen-amino-acid extension is added to the N-terminus. Together they stop it binding the IGF binding proteins that normally sequester circulating IGF-1.
Only free IGF-1 is active, so taking the binding proteins out of the equation makes LR3 roughly two to three times more potent than native IGF-1. It does not make it longer acting: in animal pharmacokinetics LR3 is cleared from plasma faster than native IGF-1, because the binding proteins it escapes are also what keep IGF-1 in circulation. It was developed as a cell-culture supplement and a livestock research reagent, and that remains its only legitimate market.
There are no human trials of LR3. Everything here is extrapolated from rodent work, cell culture, and what is known about native IGF-1 in humans, where recombinant IGF-1 is an approved drug for severe IGF-1 deficiency. Two risks follow directly from the pharmacology and are not theoretical: hypoglycaemia, because IGF-1 has meaningful insulin receptor activity, and mitogenicity, because IGF-1 drives cell proliferation indiscriminately.
How it works
LR3 binds the IGF-1 receptor and activates the PI3K/Akt and MAPK pathways, driving protein synthesis, satellite cell proliferation and differentiation, and suppression of protein breakdown. It also has weak but non-trivial affinity for the insulin receptor, which is where the hypoglycaemia comes from.
The modifications do not change what the receptor does; they change how much peptide reaches it. Native IGF-1 is over 95 percent bound to IGFBPs in circulation, which both limits its activity and shields tissues from it. LR3 largely escapes that control, which is why it works at low microgram doses, and why the same escape removes a safety buffer that exists for a reason.
Dosing
Hypoglycaemia is the acute danger. Do not combine with insulin without glucose monitoring, and do not inject before fasted cardio or before driving.
Reconstitution calculator
Pre-loaded with IGF-1 LR3’s vial size, water volume and typical dose. Change anything.
Typical: 40 mcg · range 20–80
Draw to
8 u
0.08 mL · 40 mcg
Concentration
0.5 mg/mL
5 mcg per unit
Doses per vial
25
Vial lasts
3 weeks 4 days
Draw to 8 units on the barrel.
Once mixed
2-8 degrees C and used within about 2-4 weeks in bacteriostatic water, or up to roughly 6 weeks in acetic acid. Do not freeze once reconstituted.
1 mg in 2 mL gives 500 mcg per mL, so a 40 mcg dose is 8 units on a U100 insulin syringe; using only 1 mL leaves doses too small to draw accurately. Bacteriostatic water is what most people use and is fine for a few weeks. 0.6 percent acetic acid keeps the peptide stable longer but stings noticeably going in.
Storage
Before mixing
Best at -20 degrees C for long-term storage; 2-8 degrees C is acceptable for a few weeks. It is a protein, so heat and repeated freeze-thaw cycles both degrade it.
After mixing
2-8 degrees C and used within about 2-4 weeks in bacteriostatic water, or up to roughly 6 weeks in acetic acid. Do not freeze once reconstituted.
Reported benefits
- ▪Drives muscle protein synthesis directly, with no pituitary response required
- ▪Activates satellite cells, the pathway behind adding new myonuclei
- ▪Two to three times more potent than native IGF-1 at the same molar dose
- ▪Improves nutrient partitioning and glucose uptake into muscle
- ▪Active at low microgram doses, so a single 1 mg vial covers a full run
- ▪Frequently reported to improve gut nutrient absorption, though this is anecdotal rather than measured
Side effects
- ▪Hypoglycaemia: shakiness, sweating, confusion and hunger within an hour of injecting
- ▪Marked lethargy and drowsiness for an hour or two after a dose
- ▪Headaches, particularly above about 50 mcg
- ▪Joint and jaw aches on higher doses or longer runs
- ▪Localised swelling and soreness at the injection site
- ▪Suppresses the natural GH axis through negative feedback while it is being run
- ▪Promotes proliferation in any tissue carrying IGF-1 receptors, not only muscle
Do not use if
- ▪Any active malignancy or recent cancer history; circulating IGF-1 is associated with increased risk of several common cancers
- ▪Strong family history of hormone-sensitive cancers, particularly prostate, breast or colorectal
- ▪Proliferative retinopathy
- ▪Hypoglycaemia unawareness, or concurrent insulin use without glucose monitoring
- ▪Existing cardiac hypertrophy
Evidence level — Animal only
Preclinical animal data — no meaningful human trials.
Not approved for human use in any country; sold as a cell-culture and research reagent, and prohibited in sport by WADA.
Commonly run with
HGH
Recombinant human growth hormone, the reference compound every GH peptide tries to imitate.
2 IU · Once daily, split into two injections above about 4 IU
MK-677
Oral ghrelin mimetic that raises GH and IGF-1 for a full 24 hours from one daily dose.
10 mg · Once daily
PEG-MGF
PEGylated IGF-1Ec E-peptide used after training to extend satellite-cell signalling.
200 mcg · 2x weekly
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
IGF-1 LR3 FAQ
Does injecting a muscle make that muscle grow?+
Not meaningfully. The site-injection idea traces back to rodent studies using local IGF-1 gene transfer, not to subcutaneous LR3, which distributes systemically within hours. The pump and swelling people read as local growth is fluid and tissue irritation.
How dangerous is the hypoglycaemia?+
It is the thing most likely to actually hurt you at a normal dose. IGF-1 has genuine insulin receptor activity, and 40-80 mcg on an empty stomach can drop blood glucose enough to cause confusion. Keep fast carbohydrate to hand, eat shortly after dosing, and do not combine it with insulin unless you are monitoring glucose.
Why only 4-6 weeks?+
Two reasons. Receptor downregulation makes longer runs progressively less productive, and the mitogenic risk accumulates: IGF-1 does not distinguish between muscle tissue and anything else carrying the receptor. Short, infrequent blocks are the harm-reduction position.
Is LR3 better than IGF-1 DES or plain IGF-1?+
Different rather than better. LR3 escapes the binding proteins and acts systemically, which is why it is the usual choice for once-daily dosing. IGF-1 DES is far shorter acting and is used by people chasing a brief local effect. Native IGF-1 is largely wasted when injected, since binding proteins soak it up within minutes.
Bacteriostatic water or acetic acid?+
Bacteriostatic water is fine if the vial will be finished in a few weeks, and it does not sting. 0.6 percent acetic acid holds stability longer but is uncomfortable to inject. Most people use bac water and simply reconstitute smaller amounts more often.
References
- 1.Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats — Biochemical Journal (1992) PMID 1371669
- 2.Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis — The Lancet (2004) PMID 15110491
- 3.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 — Journal of Molecular Endocrinology (1992) PMID 1378742
More growth factors
ACE-031
Myostatin and activin decoy receptor; human trials were halted over bleeding side effects.
1 mg · Once weekly
Follistatin 344
Activin- and myostatin-binding protein run in short daily courses; data are animal-only.
100 mcg · Once daily
IGF-1 DES
Truncated IGF-1 analogue with roughly 10x potency and a 20-30 minute window of action.
100 mcg · Once daily
PEG-MGF
PEGylated IGF-1Ec E-peptide used after training to extend satellite-cell signalling.
200 mcg · 2x weekly