IGF-1 LR3
Also known as Long R3 IGF-1, Long Arg3 IGF-1, LR3-IGF-1, Insulin-like Growth Factor 1 Long R3
IGF-1 LR3 is a modified, long-acting version of insulin-like growth factor 1 that resists binding proteins and stays active for most of a day. People use it for muscle growth and recovery, and it carries a real risk of low blood sugar.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 20 to 50 mcg
- How often
- once daily
- Where
- Subcutaneous or intramuscular; site does not matter because it circulates for most of a day
- Timing
- After training with a meal that contains carbohydrate; never fasted and never before bed
- Effects timeline
- muscle fullness and pumps 1 to 2 weeks, recovery 2 to 4 weeks, any size change only over the full cycle with training and food
- Storage
- Lyophilized in fridge or freezer away from light; reconstituted in fridge 2 to 8 C, use within 2 to 4 weeks, handle gently and never shake
- Cycle length
- 4 to 6 weeks
- Break between
- 4 weeks
Overview
IGF-1 LR3 is a synthetic analog of human IGF-1 with an arginine substituted for glutamate at position 3 and a 13 amino acid extension at the N-terminus, making it 83 amino acids long. Both changes were engineered to stop it binding to the IGF binding proteins that normally sequester IGF-1 in blood. Free of those proteins, LR3 has roughly two to three times the biological potency of native IGF-1 and a half-life of around 20 to 30 hours rather than minutes. It was created as a cell culture reagent and remains one, with no clinical development program.
Native IGF-1 is the main downstream mediator of growth hormone. It drives muscle protein synthesis, satellite cell activation, and cartilage and bone growth. A recombinant form, mecasermin, is approved for children with severe IGF-1 deficiency, which gives some human context for what sustained IGF-1 signaling does. The LR3 version itself has essentially no human trial data. Animal and cell studies show it promotes proliferation and differentiation of muscle cells, and in livestock research it has been used to increase growth. Its reputation for building muscle in humans rests on mechanism plus anecdote.
The practical issue with LR3 is that it acts like a weak, long lasting insulin. IGF-1 shares enough structure with insulin to activate the insulin receptor at higher concentrations, and because LR3 is unbound and long acting, it can push blood glucose down for hours. Users report shakiness, sweating, and brain fog if they inject without eating. There is also a theoretical concern about promoting growth of existing tumors, since IGF-1 signaling is a known driver of cell proliferation, and the long duration of LR3 means that exposure is continuous.
How it works
IGF-1 LR3 binds the IGF-1 receptor on muscle, bone, cartilage, and other tissues, activating the PI3K-Akt-mTOR pathway that increases protein synthesis and blocks protein breakdown, and the MAPK pathway that drives satellite cell proliferation. Activated satellite cells fuse with existing muscle fibers to add nuclei, which is why LR3 is discussed in the context of hyperplasia as well as hypertrophy. Because the Arg3 substitution and N-terminal extension prevent capture by IGF binding proteins, nearly all of the injected dose is bioavailable immediately, and the extended half-life keeps receptor signaling on for most of a day. At higher concentrations it also cross-activates the insulin receptor, lowering blood glucose.
Where the research stands
Muscle growthEmerging
- Protein synthesis. Cell culture and rodent studies show increased protein synthesis and reduced breakdown; no human trial exists.
- Satellite cell activation and hyperplasia. In vitro and rodent data only; hyperplasia in adult human muscle has never been demonstrated.
- Weight gain and nitrogen retention. Rat infusion studies showed more weight gain than native IGF-1.
Growth in severe primary IGF-1 deficiencyModerate evidence
- Pediatric growth. Applies to native recombinant IGF-1 (mecasermin), an approved drug with clinical data; LR3 itself has never been tested for this.
Recovery and injuryWeak or mixed
- Tendon and muscle repair. Anecdote plus general IGF-1 biology; no LR3 specific animal or human injury data.
Fat lossWeak or mixed
- Body fat reduction. IGF-1 does not have growth hormone's lipolytic effect; any fat change reported is indirect.
- in vitroLR3 IGF-1 shows markedly reduced affinity for IGF binding proteins and around 2-3 times the in vitro potency of native IGF-1.
- rodentLR3 IGF-1 increased protein synthesis and reduced protein breakdown in cultured muscle cells and in rodent muscle.
- rodentInfusion of LR3 IGF-1 in rats increased body weight gain and nitrogen retention compared to native IGF-1.
- clinical (approved drug)Recombinant native IGF-1 (mecasermin) increases growth in children with severe primary IGF-1 deficiency and causes hypoglycemia as its main side effect.
Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Levels over time
Modeled from the half-life. Illustrative, not measured.Dosing every 24 h with a half-life of 24 h means each dose lands on top of what is left from the last one. Levels climb to about 2.0 times a single dose before settling, roughly 4 d in.
The long half-life means a single daily dose keeps the receptor signaling around the clock, which is why injection site does not matter, why the glucose drop lasts for hours, and why nothing can be undone quickly once injected.
IGF-1 LR3 dosage and protocols
Community runs are short, 4 to 6 weeks, followed by at least 4 weeks off, on the theory that IGF-1 receptors downregulate with constant stimulation and because no long term safety data exists. Start at the low end and only increase if tolerated; there is no taper.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| First cycle | 20 mcg | once daily after training, with food | Subcutaneous |
| Standard | 40 mcg | once daily after training, with food | Subcutaneous or intramuscular |
| Upper end | 50 mcg | once daily, only if lower doses were tolerated | Subcutaneous or intramuscular |
| Training days only | 40 mcg | after each session, skipping rest days | Subcutaneous or intramuscular |
Inject after training and eat a meal with carbohydrate around the same time to blunt the glucose drop. Keep fast carbohydrate on hand for the first several doses until you know your response. Do not dose before bed or during a fast. If stacked with growth hormone, inject them at different times of day so the glucose effects do not overlap.
start at 20 mcg; most people find little benefit above 50 mcg and side effects climb
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 1 mg | 2 mL | 500 mcg/mL | 4 units |
How to reconstitute IGF-1 LR3
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1
Possible shakiness, sweating, or brain fog an hour or two after dosing if food was skipped; better pumps in training.
- Week 2 to 3
Muscle fullness and vascularity, faster recovery between sessions, mild water retention or headaches in some.
- Week 4 to 6
Modest strength and size progress if training and food are in place; diminishing returns and rising side effects if the dose keeps climbing.
Interactions and stacking
HGHsynergistic
Growth hormone adds lipolysis and endogenous IGF-1; stronger anabolic effect but the glucose concern doubles.
CJC-1295 (no DAC)compatible
A milder way to add growth hormone pulses alongside direct IGF-1 signaling.
Ipamorelincompatible
Secretagogue pulses do not conflict with LR3; total IGF-1 exposure still rises.
Insulinavoid
Both lower blood glucose and the combination has caused serious hypoglycemia in community reports.
Diabetes medicationscaution
Any glucose lowering drug stacks with the insulin-like effect of LR3.
Fasting or very low carbohydrate dietscaution
Low glycogen and no incoming glucose make the hypoglycemia far more likely and harder to reverse.
Retatrutide, semaglutide, tirzepatidecaution
Appetite suppression makes it easy to under-eat around the dose, which raises hypoglycemia risk.
Safety
- ▲Hypoglycemia with shakiness, sweating, hunger, and brain fog
- ▲Headache
- ▲Water retention
- ▲Joint aches
- ▲Injection site pain or bruising
- ▲Lethargy after dosing
- ▲Hypoglycemia is the main acute risk; inject with food and keep fast carbs on hand.
- ▲IGF-1 signaling promotes cell growth indiscriminately; do not use with any history of cancer.
- ▲Long acting and unbound, so effects cannot be reversed quickly once injected.
- ▲Can cause headaches, water retention, and joint discomfort, and prolonged use may enlarge organs in theory.
- ▲Grey market quality is highly variable; underdosed and degraded product is common because the peptide is fragile.
- ■Low blood sugar symptoms recur despite eating around the dose
- ■Any new lump, growth, or cancer diagnosis, given that IGF-1 drives cell proliferation
- ■Persistent numbness, tingling, or joint swelling
- ■Unexplained abdominal bloating or distension that does not resolve
- ■Vision changes or severe headaches
Community poll
Self-reported by visitors. Not clinical evidence.IGF-1 LR3: frequently asked
Does IGF-1 LR3 need to be injected into the muscle I trained?
No. It has a half-life of nearly a day and circulates throughout the body regardless of where you inject it. Site specific injection made sense for short acting MGF or IGF-1 DES, but with LR3 it is mostly superstition.
How do I avoid low blood sugar?
Eat a meal with carbohydrate around the time of injection, start with a low dose, and keep glucose tablets or juice nearby for the first few doses until you know how you respond. Never inject before bed on an empty stomach.
Is it stronger than HGH?
It is more direct. HGH works by raising IGF-1 through the liver, so LR3 skips that step and delivers the anabolic signal itself. It does not give you the fat loss effects of growth hormone and it does not build muscle on its own without training and food.
Why is the cycle so short?
Partly because IGF-1 receptors downregulate with constant stimulation, and partly because nobody has long term safety data on sustained unbound IGF-1. Four to six weeks is a community convention, not a studied number.
References
- Long R3 IGF-1: a potent IGF-1 analog with reduced binding protein affinity. Journal of Molecular Endocrinology, 1992
- Effects of IGF-1 and LR3 IGF-1 on protein metabolism and growth in rats. Journal of Endocrinology, 1995
- Mecasermin (Increlex) prescribing information. US Food and Drug Administration, 2005