What it is
IGF-1 LR3, properly Long R3 IGF-I, is an engineered version of insulin-like growth factor 1, the hormone the liver makes in response to growth hormone. It differs from natural IGF-1 in two ways: arginine replaces glutamic acid at position 3, and a 13 amino acid extension taken from the start of pig growth hormone is added to the front. The result is an 83 amino acid protein.
It was developed in the early 1990s as a research tool, and its main use today is in the laboratory, including as a growth supplement in cell culture media. Life-science suppliers sell it labelled for research use only. It is closer to a small protein than to the short peptides elsewhere in this library.
The important thing to understand before anything else: there is essentially no human clinical data on IGF-1 LR3. Everything below comes from rats, guinea pigs, pigs and cell culture.
How it works
Natural IGF-1 circulates mostly bound to IGF-binding proteins, which act as a reservoir and a brake. Only the free fraction reaches the IGF-1 receptor. The two changes in LR3 greatly reduce binding to those proteins.
That produces a counterintuitive result, reported by Tomas and colleagues in 1992. In their rat work, LR3 bound the IGF-1 receptor about three times less well than IGF-1, yet it was roughly 2.5 times more potent at promoting growth, because far more of it stayed free. Once at the receptor, it triggers the same growth and insulin-like signals as IGF-1.
What the research found
Human studies
None that we could find. IGF-1 LR3 has not been through phase I safety testing, dose-finding, or any controlled trial in people. There is no human pharmacokinetic data, so its half-life in humans is unknown.
Animal studies
- Rats on dexamethasone (Tomas 1992). Steroid-treated rats lose weight and muscle protein. IGF-1 given by subcutaneous pump for seven days reversed much of that loss in a dose-dependent way, and the variants with reduced binding-protein affinity, LR3 among them, were more potent than IGF-1 itself.
- Guinea pigs (1995). Infused LR3 stimulated organ growth but lowered the animals' own circulating IGF-1, IGF-II and IGF-binding proteins. In other words, the body turned down its own system in response.
- Other animal work did not show clean gains. A study in pigs reported that LR3 reduced growth, GH and the pigs' own IGF-1, and in food-restricted rats it lessened weight loss but not the loss of skeletal muscle.
None of this tells you what a given dose does in a human, and animal doses should never be converted to human ones.
IGF-1 LR3 vs mecasermin (Increlex)
The contrast with the approved IGF-1 drug is the most useful way to understand the evidence gap.
| IGF-1 LR3 | Mecasermin (Increlex) | |
|---|---|---|
| Structure | 83 amino acid analogue | Natural 70 amino acid human IGF-1 |
| Binding proteins | Binds poorly | Binds normally |
| Approval | None | US FDA, 2005 |
| Indication | None | Growth failure in children aged 2 and over with severe primary IGF-1 deficiency, or GH gene deletion with neutralising antibodies to GH |
| Human data | None | Paediatric trials and years of post-marketing data |
| Key label warnings | Unknown | Hypoglycaemia, intracranial hypertension, lymphoid tissue enlargement, slipped capital femoral epiphysis, scoliosis progression, malignant neoplasia |
The label for mecasermin tells patients to take it within 20 minutes of a meal or snack because of the hypoglycaemia risk, and states it is not a substitute for growth hormone. That is the known risk profile of a drug with normal binding-protein behaviour. An analogue designed to stay more free and act more strongly would not be expected to be gentler, and nobody has measured it.
Side effects reported in studies
There are no human side effect data. Theoretical risks follow from IGF-1 biology and from the mecasermin label above: low blood sugar, fluid and pressure effects, overgrowth of lymphoid tissue, and the long-standing question of IGF-1 signalling and cancer. The guinea pig finding that LR3 suppresses the body's own IGF system is a further unknown.
For compounds that raise IGF-1 indirectly through the pituitary, where feedback still operates, see tesamorelin, sermorelin and MK-677.
Status in the Philippines
IGF-1 LR3 is not registered with FDA Philippines and is not approved as a medicine in any country. It is sold by research-chemical suppliers and by life-science companies for cell culture. The WADA Prohibited List bans IGF-1 and its analogues under section S2 at all times.
Storage
Laboratory suppliers of LR3 specify freezer storage for the lyophilised protein, refrigeration for up to a month after reconstitution under sterile conditions, and avoiding repeated freeze-thaw cycles. A protein of this size is less forgiving of heat than a short peptide, which matters in a Manila summer or a brownout.
