Ipamorelin: What the Evidence Says About This Selective GH Secretagogue

What it is

Ghrelin, the hunger hormone, also tells the pituitary to release growth hormone. The first lab-made copies of that signal, GHRP-6 and GHRP-2, worked but came with baggage: they raised cortisol and prolactin and made people ravenous. Novo Nordisk designed ipamorelin in the 1990s to keep the growth hormone effect and lose the rest. It is five amino acids long, and in the study that matters it did exactly that (Raun et al., 1998).

It is now the most popular ghrelin-type peptide, almost always injected together with a GHRH-type peptide such as CJC-1295. It has never been approved for anything.

What it is studied for

Growth hormone release in people. Restarting the gut after abdominal surgery, in a trial that went nowhere. Lean mass in pigs and bone density in rats. The uses it is sold for, muscle, recovery, fat loss, anti-aging, have never been tested in a human trial.

What the evidence actually shows

In humans

A Phase I study gave healthy men intravenous ipamorelin at rising doses. Growth hormone rose in proportion to the dose, peaked about 40 minutes after injection, and was back to baseline within two to three hours. At every dose, including the highest, cortisol and prolactin did not move (Hansen et al., 1999). That single study is the basis for the word “selective,” and it holds up.

The only other human work was a Phase II trial of ipamorelin infusion in patients recovering from bowel surgery, testing whether a ghrelin mimic could get the gut moving again, an effect seen in dogs (Greenwood-Van Meerveld et al., 2007). The trial did not show a clear benefit and the program was dropped. Its value now is as a few days of human safety data at doses well above what users take.

That is all of it. No human study has measured what weeks or months of ipamorelin do to muscle, fat, bone, or anything else.

In animals

In growth-hormone-deficient pigs, 15 days of ipamorelin increased weight gain, mostly as lean tissue (Raun et al., 1998). In adult rats, ipamorelin and GHRP-6 increased bone mineral content in proportion to dose, alongside higher IGF-1 (Svensson et al., 2000). Both are consistent with what more growth hormone does; neither has been repeated in people.

From user reports

Better sleep with a bedtime dose is the most consistent report. Then, over 8 to 12 weeks stacked with a GHRH peptide and training: faster recovery, slow fat loss, mild water retention, and occasional tingling in the hands. Compared with GHRP-2, users describe far less hunger. None of this has been measured.

How it works

Ipamorelin binds the ghrelin receptor on pituitary cells and triggers a growth hormone pulse; the pulse raises IGF-1. Because it clears within hours, growth hormone stays pulsatile, the way the body releases it, and the normal feedback stays intact. The ghrelin receptor also drives hunger, cortisol, and prolactin, and ipamorelin’s structure happens to activate the growth hormone branch far more than the others, which is what “selective” means here.

It pairs with GHRH-type peptides because they work on a different receptor and because ghrelin-type peptides partly release somatostatin, the brake on growth hormone. Together the pulse is much larger than either alone; see the stacks guide.

How it is used in studies

The human dosing study used single intravenous doses up to 1 microgram per kilogram. Users inject 100 to 300 micrograms under the skin, one to three times a day, fasted, with the bedtime dose considered the important one, usually with 100 micrograms of CJC-1295 without DAC in the same syringe, for 8 to 12 weeks. Vials are mixed with bacteriostatic water and refrigerated; see the storage guide. None of this dosing comes from a trial.

Side effects and unknowns

Documented in the human studies: injection-site reactions, headache, flushing. Not documented at any dose: cortisol or prolactin rises. Reported by users: water retention, tingling in the hands, tiredness after a dose, all standard growth hormone effects.

The unknowns are the class unknowns. Growth hormone opposes insulin, so blood sugar can rise over a cycle. IGF-1 goes up, and chronically high IGF-1 carries a theoretical cancer link. Whether the ghrelin receptor desensitizes with three doses a day for months has not been studied in people. Neither has anything about long-term use. See the safety guide.

How it compares

• GHRP-2 and GHRP-6: stronger single pulses, with the cortisol, prolactin, and hunger ipamorelin was built to avoid.
• Hexarelin: the strongest pulse of the group and the fastest to stop working.
• MK-677: a pill on the same receptor, active all day, with two years of human trial data and more hunger and blood-sugar effect.
• CJC-1295, sermorelin, tesamorelin: GHRH-type, the other half of the stack, not substitutes. See the muscle growth guide.

Legal status

Not approved in any country. Development stopped after the surgery trial. Sold as a research chemical, and compounding pharmacies have prepared it, a practice the FDA has moved to restrict. WADA bans it in and out of competition.

Bottom line

Ipamorelin does what it says in the one human study that checked: a clean growth hormone pulse with none of the side signals of older GHRPs. Everything people take it for, muscle, recovery, fat, aging, rests on animal data and what growth hormone does in general. It is probably the least troublesome peptide in its class, and “least troublesome” was measured over hours, not years.

References

1. Raun K, et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. PubMed
2. Hansen BS, et al. (1999). Pharmacokinetics and pharmacodynamics of the growth hormone secretagogue ipamorelin in healthy volunteers. Growth Horm IGF Res. PubMed
3. Greenwood-Van Meerveld B, et al. (2007). Preclinical studies of the effects of ipamorelin, a ghrelin mimetic, on gastric and colonic motility in the dog. Neurogastroenterol Motil. PubMed
4. Svensson J, et al. (2000). The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. PubMed

See also

• Peptide
  GHRP-2: What the Research Shows About This Second-Generation GH Secretagogue

  GHRP-2 is a six-amino-acid peptide that copies ghrelin, the hunger hormone, to make the pituitary release a pulse of growth hormone. Japan approved it as a one-dose diagnostic test; no one has trialed it as a treatment.

• Peptide
  GHRP-6: What the Research Shows About This Growth Hormone Releasing Peptide

  GHRP-6 is the six-amino-acid peptide that led to the discovery of the ghrelin receptor. It reliably releases growth hormone in people and makes them very hungry. No trial has tested it for muscle or recovery.

• Peptide
  CJC-1295: What the Evidence Says About This GHRH Analog

  CJC-1295 is a longer-lasting version of GHRH, the signal that tells the pituitary to release growth hormone. The DAC form raised GH and IGF-1 for days in one small trial; the no-DAC form (Mod GRF 1-29) has no human trial of its own.