Ipamorelin and GHRP-2 are synthetic peptides which both enhance the secretion of growth hormone. Owing to the identical physiological role, they are often mistaken to be one and same. On the contrary, both the molecules are very distinctly different from each other and they only share a common functional role. The following summary highlights a comparison between the two peptides-their similarities, differences and focused research studies.
Both the peptides are structural analogues of ghrelin, the natural peptide hormone produced in gastrointestinal tract. Ghrelin promotes release of growth hormone (GH) from the pituitary gland of the body and regulates eating behavior. It is thus also known as “hunger hormone”. The peptides also perform the same function by associating with growth hormone secretagogue receptor.

Growth Hormone Releasing Hormone (GHRH)

GHRH interacts with Growth Hormone Secretagogue Receptor (GHS-R). This interaction leads influences learning, sleep-wake cycle, memory, glucose metabolism, reward cycle and sensation of taste. GHS-R activation and stimulation lead to alteration in energy metabolism. There is a distinct shift from catabolism (use of stored energy) to anabolism (buildup of energy, repair and development of diverse tissues including muscles). This shift is mediated through increase in release of GH. The GHS-Rs are prevalent both on pituitary gland and hypothalamus. Therefore both Ipamorelin and GHRP-2 associate with the receptors and promote a two way increase in GH release. GH release is directly enhanced upon peptide-GHSR association on the pituitary glands. Hypothalamic stimulation enhances release of GHRH which in turn binds to cognate receptors on the pituitary gland and improves GH release.
The shift in energy balance is not a straight forward catabolic to anabolic change. These peptides being fat burning in nature, they act on adipocytes to enhance the mobilization of stored fat. Simultaneously there is impetus for muscle and tissue repair and building which is better known as lean body mass formation. Thus the alteration in energy homeostasis causes a complex change towards promoting lean body mass formation and thereby anabolism of tissues.

Preserving growth hormone physiology

Ipamorelin and GHRH-2 are similar in their mechanism of alteration in physiologic levels of GH. Prior to use of synthetic peptides, GH was directly administered. This brought about a direct beneficial effect of the hormone but disrupted the natural physiological level of the same. GH is known to show gradual surge and decrease in levels in a twenty four hour physiological cycle. Exogenous administration of the hormone results in sharp surges and fall in the hormone level and thus its biological effect does not sustain long. Maintenance of normal pulsatile expression cycle of GH helps to overcome side effects of sudden GH surge such as cardiac damage, joint pain, swelling and acromegaly. The use of Ipamorelin and GHRH-2 enhances the physiologic mechanisms of GH release and does not produce excess of the hormone. Thus the natural hormone level is maintained in the body and helps to overcome the side effects of sudden hormone spikes and overdose triggered by direct administration of GH.

Why do we care about the Growth Hormone?

The hormone, despite the connotation of the name, plays more profound and crucial role in influencing the physiological process beyond development and growth of long bones in children, teenagers and young adults. The hormone is ubiquitious and has various crucial roles like glucose metabolism, promoting lean mass development, tissue repair and muscle growth, fat metabolism, cardiac health, proper kidney function, liver function, and also bone health.
Across animal species studies, decrease in GH is associated with aging. This decline in hormone levels in the body happens to be both cause and outcome of the aging process. Studies have shown that exogenous supplementation of the hormone can delay the progression of aging, reverse the side effects, and improve health and lifespan as well. Research conducted at the Well-Being Institute at the University of Cambridge, there is decrease in GH level by more than half between age groups of 20-40 while in age group of 20-80 it declines by a factor of about 20. The decrease in hormone level is accompanied by reduction in muscle mass, change in brain function, increased levels of blood sugar and many more. Unfortunately, direct use of external GH brings about undesirable side effects. Hence alternative approach like use of synthetic peptides has gained prominence for evaluation of their anti-aging influence and potential side effects.

Stimulating hunger

Ipamorelin and GHRP-2 being ghrelin analogs, promote appetite similar to ghrelin. Stimulation of GHS-R not only improves food uptake but also the choice of food consumed. Studies have found that these peptides promote uptake of food which promotes lean body mass as opposed to consumption of fatty or sugar-rich foods. Hence they are studies for their potential to fight obesity.

The molecular differences between Ipamorelin and GHRP-2

The mode of action of Ipamorelin and GHRH-2 is essentially the same-stimulation of GHS-R. Interestingly, their molecular structures are different and hence they exhibit different secondary functions. Their unique structural features contribute towards their varied functional modalities. Both the peptides help in muscle growth but GHRP-2 helps in improved muscle growth and breakdown even during times of starvation by preventing muscle breakdown. GHRP-2 has been observed to inactivate Atrogin-2 and MURF1 proteins in yaks. These proteins promote muscle degradation. Thus their inactivation helps GHRP-2 in control of the same. Ongoing research focusses on the applications of GHRP-2 in regulating wastage of muscle in diseases such as cancer, aging and autoimmune disorders.
Ipamorelin controls muscle wastage in the body, though using a different pathway. It reduces nitrogen metabolism in the liver and thus regulates the muscle mass in the body. However, the effect of the peptide is not robust like GHRP-2. It does not show the same effect in the backdrop of food deprivation wherein nitrogen wasting is more enhanced.
Ipamorelin also differs from GHRH-2 in regulating bone growth and mineralization. GH improves bone mineralization and health. It does not improve bone density through GH levels but also prevents bone breakdown by inhibiting osteoclast cells. Osteoclast cells are responsible for bone breakdown. Inhibition of these cells thus helps to favor bone mineralization and improves bone growth and density. GHRH-2 on the contrary does not have relevance in this molecular process.

Sleep

GHRP-2 also helps to improve the quality of sleep. As per research, it enhances stages 3 and 4 of the sleep cycle by about 50% and REM sleep by about 20%. The end results are improved cognitive abilities, regulation of energy levels, healing of wounds and even control of blood pressure. The beneficial changes are best observed in adults since there is direct correlation between age and disturbed sleep patterns. GHRP-2 is prominently involved in improvement of sleep cycle and pattern while Ipamorelin shows limited influence.

Pain Perception

GHRP-2 has been observed to bind to one of the opioid receptors and hence help to reduce feeling of pain. Ipamorelin on the other hand shows minimal effect on pain relief. GHRP-2 is now being considered as alternative treatment for pain relief instead of opioids. The molecule helps to improve pain sensation but does not cause opioid like addiction or side effect on respiration.

Ipamorelin and GHRP-2 Research Overview

Both the molecules have been subjected to human trials. This will help in future clinical research with respect to proper dose optimization, approval of institutional review board (IRB) and so on. Ipamorelin has been used for treatment of stage I and II post-operative ileus. The trial has been discontinued midway but the data offers insight into its prolonged human use.
Both the peptides have been extensively studied in animal trials like mice, rat, pigs as well as yaks. The molecules have been tested for addressing various physiological conditions. The diverse numbers of trials provide a huge repertoire of information for further experimental design and outcome prediction.

The Bottom Line

Ipamorelin and GHRP-2 peptides have greater similarities than differences. At the same time, their unique differences make both of them extremely relevant in specific milieu. Researchers can utilize a vast source of information about the effects of these peptides obtained from prior clinical trials. This will help in determining the proper dose of the molecules for better treatment of conditions and use in both animal and human research. The choice of one over the other absolutely depends on the specific objective. Ipamorelin and GHRP-2 are not yet available for human or animal consumption. All information provided is absolutely for educational reasons only.

 

 

Disclaimer: The products mentioned are not for human or animal consumption. All the information shared in this article is for educational purposes only.

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