IGF-1 LR3: a cell-culture reagent, not a supplement

Most searches for IGF-1 LR3 ask what the molecule is, whether it does anything, and whether it is legal to buy in the UK. The first answer shapes the other two. IGF-1 LR3 was designed in the early 1990s as a laboratory tool, and its main commercial use since has been as an ingredient in the media used to grow cells. It has never been tested as a medicine or supplement in people. Free Muscle sells IGF-1 LR3 for laboratory research only, to adults aged 18 or over, and nothing here is guidance on using it.

What is IGF-1 LR3?

Insulin-like growth factor 1 (IGF-1) is a 70-amino-acid protein hormone held together by three disulfide bonds. Growth hormone stimulates the liver to make it, and tissues such as cartilage also produce it locally, so much of what growth hormone does to tissue is carried out through IGF-1 (Rosenbloom 2009). In blood, IGF-1 travels bound to IGF-binding proteins, of which IGFBP-3 is the main one (Renehan 2004). These act as both reservoir and brake: bound IGF-1 cannot reach its receptor.

IGF-1 LR3, also written Long R3 IGF-I or Long [Arg3]-IGF-I, is an engineered analogue described in 1992 by Francis and colleagues at the CSIRO Division of Human Nutrition in Adelaide, one of a set of fusion proteins produced in E. coli. Two changes separate it from the human hormone. Arginine replaces the glutamic acid at position 3, the "R3" in the name. A 13-residue extension, the first 11 amino acids of methionyl porcine growth hormone followed by valine and asparagine, is added to the N-terminus, the "Long". The result is an 83-amino-acid chain with a calculated average mass of about 9,110 daltons, against about 7,650 for native IGF-1. The authors noted that the extension also helped the protein fold correctly during manufacture, giving high yields of active product (Francis 1992).

Is IGF-1 LR3 a peptide, a steroid or a SARM?

It is a peptide, strictly a small protein. It has no steroid structure and does not act at the androgen receptor, so it is neither a steroid nor a SARM. Nor is it a growth hormone secretagogue: MK-677 and ipamorelin prompt the pituitary to release growth hormone, whereas IGF-1 LR3 acts at the far end of the same axis, directly on the IGF-1 receptor. The article comparing MK-677, ipamorelin and somatropin covers the upstream compounds.

Why a growth factor became a cell-culture reagent

Cells grown outside the body need growth factors. For decades these came from animal serum, which varies from lot to lot and can carry contaminants. Manufacturers that grow Chinese hamster ovary (CHO) cells to make therapeutic proteins moved to serum-free media, in which insulin became the standard added growth factor. IGF-1 LR3 is used as an alternative. In a 2000 study from a US biotechnology company, two serum-free CHO lines producing recombinant cytokine receptors were grown with insulin or with LongR3. Both needed a growth factor for best performance under production conditions, and LongR3 sustained viability better than insulin in both (Morris 2000).

It suits culture because many cell lines secrete their own IGF-binding proteins, which take up native IGF-1 but largely ignore LR3. That is the setting in which IGF-1 LR3 is made and sold in volume: a defined, animal-free medium component for growing cells.

How IGF-1 LR3 works

IGF-1 acts through the type 1 IGF receptor, a tyrosine kinase closely related to the insulin receptor, whose activation drives protein synthesis, cell division and cell survival. IGF-1 also binds the insulin receptor, less strongly, which is one reason IGF-class molecules can lower blood glucose.

LR3's extra potency does not come from stronger receptor binding. In rat L6 myoblasts, a muscle-derived cell line, all the long analogues were more potent than native IGF-1 at stimulating protein and DNA synthesis and inhibiting protein breakdown. In chicken embryo fibroblasts, which secrete no detectable binding proteins, Long [Arg3]-IGF-I was less potent than native IGF-1. Potency tracked how weakly each analogue interacted with binding proteins, not receptor binding. In H35 hepatoma cells, where IGFs act through the insulin receptor, the long analogues kept a similar relative potency, so the modification did not remove insulin-receptor activity (Francis 1992). A related analogue, des(1-3)IGF-I, lacks the first three amino acids and escapes the binding proteins by truncation rather than extension.

What the published research reports

Animal studies

The key in vivo experiment used male rats of about 150 g made catabolic with the corticosteroid dexamethasone, which on its own caused weight loss and muscle protein breakdown over seven days. IGF-1 delivered by pumps implanted under the skin partly reversed this, improving body weight and nitrogen retention. LR3 and des(1-3)IGF-I were each about 2.5 times as potent as native IGF-1, even though LR3 bound the type 1 IGF receptor about three times less well. The authors linked this to a rise in plasma IGFBP-3 that would trap native IGF-1 but not the analogues. Two findings temper the headline. The IGF peptides, especially the analogues, increased gut weight by up to 45 per cent, and part of the fall in the muscle-breakdown marker may have come from the gut rather than muscle. Fractional carcass weight also stayed low in the treated groups (Tomas 1992). This was a one-week study in young steroid-treated rats, and it is not evidence about any other setting.

Human data

No clinical trial of IGF-1 LR3 in people has been published, for any purpose or by any route. Human data on IGF-1 come from the native hormone. Recombinant native IGF-1, mecasermin, had by 2009 been available by injection for nearly 20 years as an orphan treatment for rare growth hormone insensitivity, and had been used as an insulin-sensitising agent in severe insulin resistance (Rosenbloom 2009). That is the nearest human evidence, and it concerns a different molecule.

IGF-1 LR3 side effects: what is and is not known

For mecasermin, Rosenbloom's review lists hypoglycaemia as the most frequent adverse effect, followed by overgrowth of lymphoid tissue sometimes requiring removal of the tonsils or adenoids, accumulation of body fat and coarsening of the facial features. At the time of the review no diabetes trials were under way because of concern about retinopathy and other complications, and the review names the anti-apoptotic action of IGF-1, its inhibition of programmed cell death, as a cancer concern in long-term therapy (Rosenbloom 2009).

The epidemiology points the same way. A 2004 Lancet meta-analysis of 21 studies with 3,609 cancer cases found that circulating IGF-1 at the 75th percentile, compared with the 25th, was associated with higher odds of prostate cancer (odds ratio 1.49) and premenopausal breast cancer (odds ratio 1.65), associations the authors described as modest and variable between sites (Renehan 2004). That is an observational link with the body's own IGF-1, not a trial of any product. For LR3 there are no human adverse-event data at all, which is a gap, not a reassurance. Medical questions about IGF-1 belong with a doctor.

Regulatory status

Is IGF-1 LR3 legal in the UK?

IGF-1 LR3 is not listed as a controlled drug under the Misuse of Drugs Act 1971. It is not a licensed medicine: the MHRA has never granted it a marketing authorisation, and mecasermin, the IGF-1 medicine that does exist, is a different molecule. Nor is LR3 an authorised food supplement ingredient or novel food. It is therefore supplied only as a laboratory reagent and is not presented for human consumption; presenting any product like this with doses or promised results could bring it within medicines law. Free Muscle sells it on the reagent basis only, to customers aged 18 or over, and the IGF-1 LR3 collection page lists what is stocked.

European Union and United States

Neither the EMA nor the FDA has authorised IGF-1 LR3 as a medicine, and it is not an authorised novel food in the EU. In both markets it is supplied openly to laboratories and biomanufacturers as a cell-culture component.

WADA and sport testing

IGF-1 and its analogues fall under class S2 of the WADA Prohibited List (peptide hormones, growth factors, related substances and mimetics) and are prohibited at all times, in and out of competition, under the World Anti-Doping Code, which UK Anti-Doping applies. In 2008 the Center for Preventive Doping Research in Cologne published a method that isolates IGF-1 from a small plasma sample and uses liquid chromatography with tandem mass spectrometry to quantify the native hormone and detect analogues including LONGR3IGF-1 and des(1-3)IGF-1, with lower limits of detection of 20 to 50 nanograms per millilitre; the authors described the determination of all target analytes as unequivocal (Bredehöft 2008). No published administration study reports a detection window for LR3 in humans, so it is detectable and the window is not established.

Common questions

Questions about IGF-1 LR3 dosage and timing

We do not publish dosing, timing or usage guidance for any research compound. IGF-1 LR3 has never been studied in people, and the quantities in the rat work were chosen for rats under experimental conditions. Searches for "IGF-1 LR3 1mg" generally refer to the quantity of dry powder in a laboratory vial, a pack size rather than a dose. The compound is sold for laboratory research only and is not for human consumption.

Questions about IGF-1 LR3 benefits and results

We make no outcome claims for any research compound, and no before-and-after data exist because no human study has been done. Whether it is "worth it" depends only on the research question it is bought for. Forum and Reddit accounts cannot confirm what was in the vial and are not evidence.

IGF-1 LR3 nasal spray, capsules and vials

Every study cited here used the protein in solution, added to culture medium or delivered under the skin. No published study has measured absorption of IGF-1 LR3 through the nose. Taken by mouth, a protein of this size meets stomach acid and digestive enzymes that break peptide bonds, and there is no published evidence that intact LR3 crosses the gut wall. The Free Muscle product is a capsule, and we do not claim it behaves like the reagent in solution used in research. The article on whether oral peptides work explains the digestive barrier.

Where to buy IGF-1 LR3 in the UK

No regulator checks research reagents, so the seller's evidence is all there is. A credible UK listing names the analogue precisely (LR3, not just "IGF-1"), gives the capsule or vial count, carries a batch number that also appears on the pack, offers an independent certificate of analysis for that batch, ships from a named UK company and says nothing about doses or results. Free Muscle is FreeMuscle LTD of Scunthorpe. Its IGF-1 LR3 comes in bottles of 60 capsules, and UK delivery is free, tracked and in plain packaging (shipping details). The UK supplier checklist applies the same tests to any seller.

How to verify a batch

A protein of this size can be wrong in more ways than a small molecule: a different IGF variant, a truncated or misfolded chain, or native IGF-1 sold under the LR3 name. A useful certificate of analysis shows:

  1. A batch number that matches the one printed on the pack.
  2. An identity result by LC-MS, with a measured mass close to the calculated figure of about 9,110 daltons. A mass near 7,650 would point to native IGF-1, and one near 7,370 to des(1-3)IGF-I.
  3. A purity percentage by HPLC, showing how much of the material is the intact chain rather than fragments, aggregates or oxidised forms.
  4. The laboratory's name, the test date and the product name as tested.
  5. A quantity per capsule, where the laboratory measured one. The Free Muscle listing states the capsule count but not a per-capsule quantity, so the certificate is where any measured figure would appear.

Every Free Muscle-brand batch is assayed by Janoshik Analytical, and the certificate for a batch is sent on request by email; the lab tests page explains how to ask. A generic PDF without a batch number, or a raw-material certificate rather than one for the finished capsules, does not show what is in the bottle. The guide to reading a certificate of analysis works through an example.

Related reading

IGF-1 LR3 is sold by Free Muscle as a laboratory reagent for research use only. It is not a licensed medicine, has not been evaluated by the MHRA, EMA or FDA, is not a food supplement and is not for human consumption. IGF-1 and its analogues are prohibited in sport under the WADA Prohibited List. Customers must be 18 or over. Nothing in this article is medical, dosing or usage advice, and the studies described do not support any claim about any product.

References

  1. 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. J Mol Endocrinol. 1992;8(3):213-223. PMID: 1378742.
  2. 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. Biochem J. 1992;282(Pt 1):91-97. PMID: 1371669.
  3. Morris AE, Schmid J. Effects of insulin and LongR(3) on serum-free Chinese hamster ovary cell cultures expressing two recombinant proteins. Biotechnol Prog. 2000;16(5):693-697. PMID: 11027158.
  4. Rosenbloom AL. Mecasermin (recombinant human insulin-like growth factor I). Adv Ther. 2009;26(1):40-54. PMID: 19198769.
  5. Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346-1353. PMID: 15110491.
  6. Bredehöft M, Schänzer W, Thevis M. Quantification of human insulin-like growth factor-1 and qualitative detection of its analogues in plasma using liquid chromatography/electrospray ionisation tandem mass spectrometry. Rapid Commun Mass Spectrom. 2008;22(4):477-485. PMID: 18236437.