Studies in Ipamorelin for Muscle Growth and Bone Density

Ipamorelin, also known as NNC 26-0161, is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2. Researchers suggest it may induce a peak in growth hormone (GH) synthesis by the pituitary gland via activating the growth hormone secretagogue receptors (GHS-Rs). In this respect, Ipamorelin is classified as a growth hormone secretagogue (GHS). It appears mimic the hunger hormone Ghrelin, which is also a natural activator of the GHS-Rs.

Ipamorelin peptide appears to differentiate itself from other GHSs as a more selective option that elevates GH levels without increasing other pituitary hormones, such as prolactin. Studies are still underway with this peptide as a tool for managing postoperative ileus and speeding up the recovery of gastrointestinal function in patients following surgery. Ipamorelin is still under investigation for its potential to support gastrointestinal functions, increase bone mass, preserve body weight, and more.

Research

Ipamorelin and GH synthesis

Studies suggest that Ipamorelin is a highly selective growth hormone secretagogue, which may be capable of increasing GH levels in both animals and humans by activating the GHS-R receptors.^[1,2]

Research trials report that the effect occurs relatively quickly – as soon as 40 minutes after administration, there is a peak in GH levels. The scientists note that the half-life of Ipamorelin appears to be around 2 hours. Growth hormone levels return to baseline within 3 hours, and the Ipamorelin peptide remains in a person’s system for up to 9 hours. The peptide may require administration several times a day to be effective.

Increasing GH levels can have numerous potential benefits, such as preserving muscle and lean body mass, increasing energy levels, improving bone mineral density, and more. Moreover, studies report that Ipamorelin has a strong safety profile. The peptide did not show any documented adverse reactions for up to 2 weeks of use, except for minor complaints such as nausea and gastrointestinal problems.^[3] 

Ipamorelin and gastrointestinal functions

Ipamorelin has been studied for its potential to alleviate delayed gastric emptying and post-surgical ileus in both animals and humans. In rodents, the peptide may significantly accelerate the rate of gastric emptying as it stimulates gastric contractility.^[4] The route via which the peptide exhibits effects is by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.

The researchers reported that “Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%.”

Ipamorelin was also tested in 117 individuals who underwent bowel surgery for various medical reasons.^[3] The peptide was given for 7-10 days following the surgery, and 51.8% of the treatment group recovered their gastrointestinal function in that period compared to 34.5% of the placebo group. This effect did not reach statistical significance, yet, in the responder analysis, 46.4% of open-laparotomy patients receiving Ipamorelin were responders compared with 20.7% of the placebo group, which was significantly more. 

Ipamorelin and increased appetite and weight gain

Existing research suggests that Ipamorelin may increase appetite, reduce weight loss in wasting disorders, and cause weight gain in healthy subjects. This hypothesis is based primarily on animal studies.

According to the researchers, these results are due to the appetite-increasing effects of Ipamorelin.^[5] The peptide appears to activate the receptors of the hunger hormone, which in turn results in an increased food intake. The increased food intake is most prominent at the start of the therapy; later on, the effect on the appetite appears to subside.

On the other hand, the GH-increasing potential of Ipamorelin may also help reduce weight loss, especially protein loss. Studies posit that Ipamorelin may significantly reduce muscle wasting in cortisol-treated animals and help maintain a positive nitrogen balance.^[6] The researchers conclude that “Accelerated nitrogen wasting in the liver and other organs caused by prednisolone treatment was counteracted by treatment with either GH or its secretagogue Ipamorelin.”

Another trial observes that Ipamorelin appears to negate the GH-inhibiting effect of glucocorticoids in tested animals.^[7] Animal studies suggest that Ipamorelin may also stimulate insulin secretion, another anabolic hormone that can help reduce muscle loss in wasting disorders.^[8] 

Ipamorelin and bone health

Growth hormones are a known factor in maintaining optimal bone mineral density. Animal studies show that thanks to Ipamorelin’s alleged effects on growth hormone synthesis and body weight, it may help maintain or even increase bone mass.

One study on thirteen-week-old female Sprague-Dawley rats showed that Ipamorelin therapy appeared to significantly increase bone mineral content after 12 weeks.^[9] The increase was measured via a DEXA (dual-energy X-ray absorptiometry) scan and was significantly higher than the placebo group.

Another animal trial on rats treated with glucocorticoids reported that Ipamorelin has the potential to completely negate bone loss induced by glucocorticoids.^[10] The scientists report that the periosteal bone formation rate increased four-fold in animals administered with glucocorticoids and Ipamorelin in combination, compared with the group that received glucocorticoids alone. 

Conclusion

Ipamorelin is a potent growth hormone secretagogue that appears to work by mimicking the function of ghrelin and activating the GHS-R, which may lead to a peak in GH levels.

Due to these observations, researchers suggest Ipamorelin can help preserve body weight and lean body mass, increase insulin secretion, speed up stomach emptying, stimulate appetite, and increase bone mineral density. Most research is conducted on test animals, and the peptide is still under investigation. 

The peptide is currently not approved for any condition and has a status of an experimental peptide. Therefore, it should not be used outside research settings. 

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References

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2. Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999 Sep;16(9):1412-6. doi: 10.1023/a:1018955126402. PMID: 10496658.
3. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. doi: 10.1007/s00384-014-2030-8. Epub 2014 Oct 21. PMID: 25331030.
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7. Malmlöf K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats. Growth Horm IGF Res. 1999 Dec;9(6):445-50. doi: 10.1054/ghir.1999.0128. PMID: 10629165.
8. Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004 Dec;25(6):403-6. PMID: 15665799.
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