IGF-1 LR3

IGF-1 (insulin-like growth factor 1) is a 70-amino-acid hormone made mainly in the liver in response to growth hormone. IGF-1 LR3 ("Long R3") changes it in two ways: the third amino acid, glutamic acid, is replaced by arginine (the "R3"), and a 13-amino-acid extension is added to the start (the "Long"), made of the first 11 amino acids of pig growth hormone plus two linking amino acids (Francis 1992).

It was made in the early 1990s by a research group in Adelaide, Australia. The changes make it bind poorly to the IGF-binding proteins that normally hold IGF-1 in check, so more of it stays free to act on cells. In cell lines that produce these binding proteins it was more potent than normal IGF-1, even though it binds the IGF-1 receptor itself less well (Francis 1992; Tomas 1992). Its main use since then has been as a growth supplement in laboratory cell culture.

IGF-1 LR3 should not be confused with mecasermin (Increlex), a recombinant copy of natural human IGF-1 that is FDA-approved for growth failure in children with severe primary IGF-1 deficiency. Mecasermin is a different molecule, and its clinical data do not apply to IGF-1 LR3.

• Type: modified recombinant IGF-1, 83 amino acids (70 of IGF-1 plus a 13-amino-acid extension).
• Studied for: growth and protein balance in rats, blood sugar effects in pigs, and use as a cell culture additive.
• Strongest evidence: animal studies from the 1990s, mostly from the Adelaide group that developed it. No published human studies.
• Legal status: not approved as a medicine anywhere in the US; prohibited in sport by WADA.

At a glance: 7 studies report a dose (6 in animals, 1 in cells).

IGF-1 LR3 acts on the same receptor as natural IGF-1. What differs is how much of it is free to act:

• Escape from binding proteins: the arginine at position 3 and the N-terminal extension reduce binding to IGF-binding proteins, so more of the peptide reaches cells (Francis 1992).
• Weaker receptor binding, stronger effect: it binds the IGF-1 receptor about 3 times less well than IGF-1 but was still about 2.5 times more potent in rats (Tomas 1992).
• Insulin-like action: like IGF-1 it lowers blood sugar, and more strongly and for longer than IGF-1 in pigs (Tomas 1997).

1. Wash your hands and work on a clean, uncluttered surface. Let a refrigerated vial reach room temperature so the stopper is easier to pierce.
2. Wipe the rubber stopper of the peptide vial and of the bacteriostatic water with a fresh alcohol swab, and let them air-dry.
3. Draw the chosen volume of bacteriostatic water into a sterile syringe. With 2 mL, a 1 mg vial ends up at 500 mcg/mL, or 5 mcg per U-100 unit.
4. Insert the needle through the stopper and let the water run slowly down the inside wall of the vial, not straight onto the powder.
5. Swirl or roll the vial gently until the powder dissolves. Do not shake it: foaming can damage some peptides.
6. Check the solution against the light. It should be clear; cloudiness or particles mean something is wrong with the vial or the water.
7. Write the date and the volume of water on the label. Every unit calculation later depends on that volume.
8. Store the reconstituted IGF-1 LR3 vial in the refrigerator, away from light.

• A U-100 insulin syringe holds 1 mL in 100 units, so each unit is 0.01 mL. The marks measure volume, not peptide.
• Syringes come in 0.3 mL (30 units), 0.5 mL (50 units) and 1 mL (100 units) sizes. The smaller ones have finer marks and are easier to read for small volumes.
• Read the volume at the top edge of the plunger's rubber seal, at eye level.
• Tap out air bubbles before reading: a bubble takes up volume and makes the reading wrong.
• Use a new sterile syringe and needle every time, and dispose of them in a sharps container.

• The peptide vial, with its certificate of analysis (COA) for that batch. See how to read a COA.
• Bacteriostatic water (water with 0.9% benzyl alcohol), which keeps a multi-use vial from growing bacteria. Sterile water has no preservative.
• Sterile syringes to add the water, and U-100 insulin syringes to measure.
• Alcohol swabs for the stoppers.
• A sharps container for used needles.
• A label or marker to write the date and the volume of water on the vial.

There are no human safety data. Everything known about its effects comes from rats, mice, pigs and cells.

• Low blood sugar: in pigs it caused stronger and longer-lasting drops in blood sugar than IGF-1 (Tomas 1997). Severe low blood sugar is a listed risk even for the approved IGF-1 drug mecasermin.
• Cell growth: IGF-1 is a growth signal for many cells, including some cancer cells. The long-term effects of a more potent, unregulated IGF-1 analogue are unknown.
• Product quality: a doping control lab found a black market vial containing a laboratory form of Long R3 IGF-1 with a purification tag still attached, a version made for research use whose effects in people are unknown (Kohler 2010).
• Injection risks: any injected product that is not sterile can cause infection or abscesses.
• Sport: IGF-1 and its analogues are on the WADA prohibited list at all times.

Before mixing

• Freeze-dried (lyophilised) peptide is the most stable form. It is usually kept refrigerated, or frozen for long storage, sealed and away from light.
• Heat, moisture and light speed up degradation. Keep the vial in its box and avoid leaving it in a car or by a window.

After mixing

• Keep the reconstituted vial refrigerated and away from light. Do not freeze it again: freezing and thawing a solution can break the peptide down.
• How long a mixed vial stays good depends on the peptide and the diluent, and for most research peptides there is no published stability data. Follow the supplier's guidance and discard any vial that turns cloudy.
• Pierce the stopper as few times as possible, and always with a new sterile needle after wiping it with alcohol.
• Write the volume of water on the label (for example "2 mL"). Without it, the unit calculations cannot be checked later.