Ipamorelin vs GHRP-2

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Ipamorelin vs GHRP-2​

Many people think that ipamorelin and GHRP-2 are the essentially the same thing. After all, both cause an increase in the secretion of growth hormone (GH). In reality, ipamorelin and GHRP-2 are very different peptides and the fact that they cause GH hormone release is the only thing they really share in common. Below is summary of ipamorelin vs GHRP-2 that outlines the similarities, differences in their respective research studies.

Both ipamorelin and GHRP-2 cause the pituitary gland to release more growth hormone by binding to the growth hormone secretagogue receptor. This means that both peptides are analogues of ghrelin. Ghrelin, a naturally occurring peptide produced in the gastrointestinal tract, is often referred to as the hunger hormone as it stimulates eating behavior. It does so much more than that though.

Growth Hormone Releasing Hormone (GHRH).

Stimulation of the growth hormone secretagogue receptor (GHS-R) has effects on learning, memory, the sleep-wake cycle (diurnal cycle), reward behavior, glucose metabolism, and even taste sensation. Most importantly, stimulating this receptor impacts energy balance in the body, helping to shift the body from catabolism (the breakdown of stored energy) to anabolism (the storage of energy and the repair and building of muscle and other tissue). This shift occurs via the stimulation of GH release. GHS-Rs are found on both the hypothalamus and the pituitary gland, which means that peptides like ipamorelin and GHRP-2 have a two-pronged approach for stimulating growth hormone release. The first is via direct stimulation of the pituitary gland where GH is stored and the second is via the release of GHRH, which has its own receptors on the pituitary gland for stimulating GH release.



Ghrelin Axis: Note that ghrelin and its analogues (GHRP-2 and ipamorelin) stimulate the release of growth hormone in two different ways, both directly by binding to GHS-Rs on the pituitary gland and indirectly by binding to GHS-Rs in the hypothalamus and causing the release of growth hormone.

Of course, the shift isn’t quite that simple because both GHRP-2 and ipamorelin encourage the body to burn fat and build lean body mass (muscle and bone). Thus, they shift the energy balance in a more complex way than the simple catabolic/anabolic dichotomy would suggest. The best way to think of these peptides, and indeed any peptide that stimulates the GHS-R, is as promoting lean body mass. These are muscle repair/building, fat-burning peptides at their core, but they offer so much more than that.

Preserving Growth Hormone Physiology​

Another way in which ipamorelin and GHRP-2 are similar is in their preservation of normal growth hormone physiology. Until recently, the only way to elevate levels of GH was to administer GH directly via injection. This is an effective strategy, but suffers from one major drawback. Normally, growth hormone is released in a pulsatile, episodic manner. In other words, GH levels wax and wane throughout a 24-hour cycle and the rises and falls are gentle, not abrupt [1-3]. Exogenous administration of GH produces what is referred to as a square wave, with an abrupt rise to high levels, a short period of activity (the half-life of GH is just 15-20 minutes) and then an equally abrupt fall. The figure below illustrates the difference between pulsatile and square-wave GH cycling.



Now, it may seem inconsequential whether GH levels rise abruptly or not, but studies indicate that preserving normal pulsatile secretion patterns can help to prevent side effects commonly seen with GH administration including acromegaly, joint pain, heart damage, and swelling. As an added bonus, because GHRP-2 and ipamorelin are working with the physiological mechanisms rather than in addition to them, normal feedback controls continue to operate. These controls help to prevent GH overdoses, which is to say spikes that are so great they cause problems[1].

Why Do We Care About Growth Hormone?​

Growth hormone, despite what its name suggests, is more than simply a driver of long bone growth amongst children, teens, and young adults. This ubiquitous hormone plays important roles in everything from maintaining appropriate body composition (muscle vs fat balance) to protecting bone health, heart health, kidney function, liver function, and even glucose metabolism.

It is a well-known fact, across every animal species ever studied, that decreases in GH levels are associated with aging. This is both a cause of aging and a consequence of aging, posing one of the more profound “chicken-or-egg” conundrums in human physiology. What is clear, however, is that research supports the position that supplementing with GH can help to offset the effects of aging and prolong health span if not lifespan as well.

According to The Well-Being Institute at the University of Cambridge, growth hormone levels drop by more than half between the ages of 20 and 40. They drop by a factor of 20 between the ages of 20 and 80. This leads to higher levels of blood sugar, loss of muscle mass, changes in brain function, and much more. Unfortunately, supplementing with straight human growth hormone has a number of undesirable side effects. Thus, researchers have been exploring alternatives, such as ipamorelin and GHRP-2, to determine their potential anti-aging benefits and side effect profiles[4].

Stimulating Hunger​

Because both ipamorelin and GHRP-2 are ghrelin analogues, they stimulate appetite in much the same way that ghrelin does. This means they promote food intake. Interestingly, stimulation of the GHS-R not only promotes food intake, but it alters the types of food consumed. Research shows that ghrelin and its analogues stimulate the intake of foods that promote lean body mass versus fatty or sugar-rich foods. It is for this reason that these peptides have been investigated for their potential to help fight obesity[5, 6].

The Molecular Differences​

So GHRP- and ipamorelin share a great deal in common. Most important among their shared attributes is the fact that they both bind to and activate the GHS-R. The peptides are not, however, identical. They have different structures and, as a result, different secondary functions.









Ipamorelin

Source: PubChem



GHRP-2

Source: PubChem

These structural differences have certain impacts on the benefits these two peptides confirm. For instance, while both promote muscle growth, GHRP-2 offers improved muscle growth and protection, even during times of starvation, by preventing muscle breakdown. Research in yaks shows that GHRP-2 inactivates the atrogin-2 and MuRF1 proteins that are critical in the control of muscle degradation. Scientists are investigating how this feature of GHRP-2 might be used in the muscle wasting common in chronic autoimmune diseases, cancer, and aging[1, 7].

Ipamorelin also helps to reduce muscle wasting, but it does so in a different way, decreasing the loss of nitrogen in the liver. This leads to improved nitrogen balance and thus less muscle breakdown. This process, however, is not as robust as that seen with GHRP-2 and does not show the same effects in the setting of food deprivation when normal mitigation of nitrogen wasting is more pronounced[8].

Another profound difference of GHRP-2 vs ipamorelin is in bone health. While GH, in general, promotes bone growth and improve mineralization (increased bone density), ipamorelin appears to have benefits for bone health that go beyond simply stimulating GH release. Bone health is a balance between bone loss and bone deposition. In healthy individuals, these processes are generally in balance such that a slight increase in bone deposition rates caused by GH will lead to an overall increase in bone growth/density. In unhealthy individuals, the process if often tiled away from bone deposition and toward bone breakdown. Ipamorelin, it turns out, can halt bone breakdown, probably by inhibiting the function of the cells (osteoclasts) responsible for this process. While GHRP-2 has minimal effects in this particular area, ipamorelin has significant, well-studied abilities to promote bone density[9, 10].

Sleep​

GHRP-2 is benefits in improving sleep quality. Research shows that GHRP-2 increases the duration of stages 3 and 4 in the sleep cycle by about 50% and REM sleep by about 20%. This leads to improvements in cognitive function, wound healing, energy levels, and even blood pressure. These effects are most profound in elderly adults, which is unsurprising given the known association between age and disordered sleep. While ipamorelin does have some benefit in promoting healthy sleep, research shows that GHRP-2 can reduce deviations from normal sleep patterns by as much as a third, a dramatic benefit[11].

Pain Perception​

It turns out that GHRP-2 binds to one of the opioid receptors and, as a result, can help to mitigate pain. Ipamorelin has shown no such proclivity and appears to have minimal effect on pain perception. GHRP-2 is being investigated as a potential starting point for developing pain-reliving medications that are similar to opioids but do not have the same addictive potential or effect on respiration[12].

Research Overview​

Both ipamorelin and GHRP-2 have been utilized in human trials, a fact that might make future research easier by providing a starting point for dosing, institutional review board (IRB) approval, and more. Ipamorelin has undergone stage I and II clinical trials for the treatment of post-operative ileus. While that research was eventually abandoned, it does offer insight into the use of the peptide in prolonged human trials. This may be useful for certain research interests looking to examine the effects of the peptide in humans.

Both GHRP-2 and ipamorelin have been extensively tested in animal trials. While the primary research is carried out in mice and rats, trials in other animals, such as pigs and yaks, have been conducted. Thus, there is a broad basis for testing these peptides in various models. Researchers looking to investigate the effects of these peptides therefore have a number of trials from which to draw upon for experimental design and outcome prediction.

The Bottom Line​

Ipamorelin and GHRP-2 are more similar than they are different. That is not to say, however, that one does not offer benefits over the other that might be of interest in certain settings. People interested in exploring the effects of these to ghrelin analogues should take a long, hard look at the available literature as there is an abundance of information to inform dosing and expected effects in both animal and human research. Ultimately, there is no way to say that one is “better” than the other. They are similar and they are different. Which peptide will be of most use in the research setting will depend upon the specific goals of that research.

Resources​

[1]K. Raun et al., “Ipamorelin, the first selective growth hormone secretagogue,” Eur. J. Endocrinol., vol. 139, no. 5, pp. 552–561, Nov. 1998.



[2]R. Hu et al., “Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation,” PloS One, vol. 11, no. 2, p. e0149461, 2016.

[3]L. T. Phung et al., “The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine,” Domest. Anim. Endocrinol., vol. 18, no. 3, pp. 279–291, Apr. 2000.