In studies IGF-1 LR3 acted 2 to 3 times more strongly than natural IGF-1, and in healthy growing rats as much as about 6 times more strongly. A dose of 44 micrograms a day gave the same body weight gain, nitrogen retention and feed use as 278 micrograms of ordinary IGF-1. In wasting animals LR3 held back the loss of body weight and the breakdown of muscle protein, and protein synthesis in muscle rose by as much as 50 percent. Below we gather these results and explain where LR3's advantage over ordinary IGF-1 comes from.
What is IGF-1 LR3?
IGF-1 is insulin-like growth factor, through which growth hormone acts on muscle, bone and many other tissues. LR3 is a modified version of it, described in 1992 by researchers from the Australian science agency CSIRO in Adelaide. It differs from natural IGF-1 in two changes:
- the letters R3: at the third position of the chain glutamic acid was replaced with arginine,
- the letter L, for "long": a short stretch of extra amino acids was added at the start of the chain.
Both changes make LR3 bind very weakly to the IGF binding proteins, IGFBP for short. A comparison with the other modification, DES(1-3) IGF-1, is in the guide on how IGF-1 LR3 and DES(1-3) IGF-1 differ.
Why does LR3 act more strongly than ordinary IGF-1?
Natural IGF-1 binds to IGFBP proteins in the blood. These proteins hold it tightly and limit its passage from the blood into tissues. LR3 hardly binds to them at all, so it reaches its target cells more freely.
Interestingly, LR3 itself binds the IGF-1 receptor about 3 times more weakly than the natural factor. Even so it acted more strongly, simply because more of it reached the receptor. The Adelaide researchers linked LR3's advantage to the fact that the binding proteins did not cut it off from tissues.
What did studies on muscle cells show?
The first comparison was published in 1992. The researchers tested several extended versions of IGF-1 on rat myoblasts, the cells that form muscle fibres. All the extended versions stimulated protein and DNA synthesis and inhibited protein breakdown more strongly than ordinary IGF-1.
The strongest was the version with arginine at the third position, that is LR3, on a par with DES(1-3) IGF-1. In cells that do not secrete IGFBP proteins, LR3 acted more weakly than ordinary IGF-1. This confirmed that LR3's strength comes from bypassing the binding proteins, not from a stronger action on the receptor itself.
What effects did IGF-1 LR3 have in animals?
The Adelaide team tested LR3 in several rat models. In most studies the peptide was given continuously through a small pump implanted under the skin.
| Study | Model | LR3 result |
|---|---|---|
| Tomas, 1992 | rats wasted with dexamethasone, 7 days | about 2.5 times stronger than IGF-1 at limiting weight loss |
| Tomas, 1993 | healthy growing female rats, 14 days | 44 µg a day had the effect of 278 µg of IGF-1 |
| Tomas, 1993 | diabetic rats, 7 days | 2.5 to 3 times stronger at restoring growth |
| Lemmey, 1994 | rats after removal of part of the gut | better weight gain and food use |
In healthy female rats the highest dose of ordinary IGF-1 increased weight gain, nitrogen retention and feed use by 18 to 26 percent. Body and organ proportions were preserved. In diabetic rats all the tested peptides increased protein synthesis in muscle by as much as 50 percent, and ordinary IGF-1 was the weakest.
Does IGF-1 LR3 protect muscle from breakdown?
Yes, in a 1992 study in rats wasted with dexamethasone, a steroid that breaks down protein. Untreated animals lost 19 grams in a week. The highest dose of ordinary IGF-1 turned this loss into a gain of 6 grams, and LR3 acted about 2.5 times more strongly in this study.
The researchers also measured protein synthesis in muscle and the breakdown of muscle fibres. The peptides acted on both processes at once: they increased protein building and limited its breakdown. The body weight gain came from added nitrogen, that is protein, and not from fat.
Does an injection once a day work too?
A 1996 study tested this, because earlier work used pumps with continuous delivery. Rats received LR3 or ordinary IGF-1 for 7 days, once or twice a day by subcutaneous injection.
- Continuous delivery worked best, especially against wasting.
- LR3 injected once a day still outperformed ordinary IGF-1 on several results.
- Muscle protein breakdown fell three times more after LR3 injections than after IGF-1 injections.
In protecting whole-body muscle mass during wasting, both injected peptides performed similarly. The authors concluded that LR3's advantage holds with injections, although it is smaller than with continuous delivery.
What should you watch for with IGF-1 LR3?
IGF-1 acts in a similar way to insulin and lowers blood sugar. In a 1997 study in pigs and marmosets, variants that bind weakly to IGFBP lowered blood sugar 2 to 3 times more strongly than ordinary IGF-1. The drop also lasted longer, and the total effect over four hours was about 2 times greater at doses of equal strength.
That is why the fall in blood sugar matters with IGF-1 LR3, and it has not yet been studied in humans. No clinical trials of LR3 in humans have been published. IGF-1 LR3 is not an approved medicine. How IGF-1 links with other muscle-building pathways is explained in the guide on muscle peptides: the IGF-1 axis, MGF and myostatin.
Where to buy IGF-1 LR3 and how much does it cost?
The shop has three 1 mg vials of IGF-1 LR3:
| Product | Price | Availability |
|---|---|---|
| IGF-1 LR3 1 mg Bio-Peptide | 65 EUR | in stock |
| IGF-1 LR3 1 mg Genheal | 65 EUR | on backorder |
| IGF-1 LR3 1 mg Nouveaux Ltd. | 75 EUR | in stock |
All variants are gathered on the IGF-1 LR3 page. Other molecules that act on muscle growth are covered in the guides on follistatin 344 and ACE-031. The products in the shop are material for laboratory research, not a medicine.
Frequently asked questions
How much stronger is IGF-1 LR3 than ordinary IGF-1?
In rat studies 2 to 3 times. In healthy growing rats 44 micrograms of LR3 gave the same effect as 278 micrograms of ordinary IGF-1.
Why does IGF-1 LR3 act more strongly?
LR3 binds very weakly to the IGFBP proteins that hold ordinary IGF-1 in the blood. This lets it reach tissues more easily, even though it binds the receptor itself more weakly.
Does IGF-1 LR3 act on muscle?
In rat studies IGF-1 peptides increased protein synthesis in muscle by as much as 50 percent and held back its breakdown during wasting, and LR3 acted more strongly than ordinary IGF-1.
Does IGF-1 LR3 lower blood sugar?
Yes, in pigs and marmosets IGF-1 variants that bind weakly to IGFBP lowered blood sugar 2 to 3 times more strongly and for longer than ordinary IGF-1.
How much does IGF-1 LR3 cost in the shop?
A 1 mg vial costs 65 EUR from Bio-Peptide and Genheal and 75 EUR from Nouveaux Ltd.
Sources
- Francis GL, Ross M, Ballard FJ et al. 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, 8(3): 213-223. https://doi.org/10.1677/jme.0.0080213
- Tomas FM, Knowles SE, Owens PC et al. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochemical Journal, 1992, 282(1): 91-97. https://doi.org/10.1042/bj2820091
- Tomas FM, Knowles SE, Chandler CS et al. Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats. Journal of Endocrinology, 1993, 137(3): 413-421. https://doi.org/10.1677/joe.0.1370413
- Tomas FM, Knowles SE, Owens PC et al. Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects. Biochemical Journal, 1993, 291(3): 781-786. https://doi.org/10.1042/bj2910781
- Lemmey AB, Ballard FJ, Martin AA et al. Treatment with IGF-I peptides improves function of the remnant gut following small bowel resection in rats. Growth Factors, 1994, 10(4): 243-252. https://doi.org/10.3109/08977199409010990
- Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. Journal of Endocrinology, 1996, 150(1): 77-84. https://doi.org/10.1677/joe.0.1500077
- Tomas FM, Walton PE, Dunshea FR, Ballard FJ. IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. Journal of Endocrinology, 1997, 155(2): 377-386. https://doi.org/10.1677/joe.0.1550377