What Is Ipamorelin?

In the world of anti-aging research, a handful of peptides have become superstars. Ipamorelin is one of those peptides. This short peptide is just five amino acids in length, but is one of the most selective growth hormone secretagogue receptor agonists known. This means that ipamorelin research has been shown to help build lean body mass and fight obesity without having unwanted effects on other aspects of the body like hair growth or decreased sexual function[1].

Ipamorelin is a peptide, which means it is made of the same amino acid building blocks found in all proteins. Ipamorelin falls into the subcategory of anti-aging peptides as well as into the subcategory of fat-burning peptides. In animal studies, it has been shown to effectively fight the signs of aging while benefiting muscle growth, bone health, and GI system function.

Because of its relative lack of secondary effects, ipamorelin is often referred to as the gentle growth hormone releasing peptide. This is because, when compared to other peptides like Sermorelin or GHRP-6, Ipamorelin tends to only affect the growth hormone axis. This makes it particularly useful in research exploring the isolated effects of growth hormone secretagogue agonists.

How Does Ipamorelin Work?

Ipamorelin binds to and activates the ghrelin (growth hormone secretagogue) receptor. The ghrelin receptor (a.k.a. GHS-R) is an important regulator of energy balance in the body as well as overall body weight. It is found extensively in the brain but is also found in the liver, heart, and skeletal muscle.

In the brain, the primary function of the GHS-R is to cause the release of growth hormone from the pituitary gland. Unlike other GHS-R agonists, Ipamorelin is highly exclusive for growth hormone release. It does not affect other hormones, like ACTH and prolactin, in any significant way.

Ipamorelin has a short half-life of just 2 hours. This means that the peptide is functionally removed from the body after just 6 hours. This makes ipamorelin ideal for use in research exploring the benefits of growth hormone stimulation in relation to specific other physiologic events such as food consumption, exercise, stress, etc.

How Does Ipamorelin Fight Aging?

Bone loss, muscle wasting, changes in appetite, and declines in memory and cognitive function are all associated with aging. Though doctors consider each of these to be pathological and not a part of normal aging, there is no denying that as the body begins to lose its ability to generate certain hormones, a number of biochemical pathways begin to deteriorate. By fighting this deterioration, Ipamorelin can help to thwart some of the effects of aging. In the case of bone, for instance, aging is associated with an increase in the activity of cells called osteoclasts. These cells are responsible for bone breakdown and play a useful role in help bone to remodel itself following injury or during stress (e.g. lifting weights). Too many osteoclasts, however, means that bone breakdown is more rapid than bone formation and overall bone density begins to decrease. Ipamorelin appears to help restore balance to the bone cycle, helping to ensure that breakdown and deposition occur at just the right rates to ensure proper bone strength and function[2]. This is just one of the ways in which ipamorelin helps to create what might be termed a youthful physiological state.

Ipamorelin and Fat Loss

Ipamorelin is a multifaceted peptide with a number of effects. Though it is generally categorized as an anti-aging peptide, a classification that best reflects ipamorelin’s diverse effects, it could just as easily be called a lipogenic or fat-burning peptide. Research in mice shows that Ipamorelin accelerates the process of lipolysis, the structured breakdown of fat. Though a great deal of this effect can be attributed to ipamorelin’s ability to stimulate hGH release, there is evidence in animal studies to suggest a secondary mechanism as well.

In studies of rats, ipamorelin has been shown to potentiate insulin release. Insulin is an anabolic hormone, favoring the storage of glucose in a variety of ways in muscle, fat, and the liver. It may seem contradictory that ipamorelin can boost fat burning if it also stimulates the release of insulin, but there is a reason for this dichotomy. Insulin generally takes the path of least resistance when directing glucose. Thus, if muscle tissue is more readily accepting glucose, then it will be preferentially stored there. By potentiating the release of insulin at the same time it stimulates hGH release, Ipamorelin helps to ensure that more dietary calories go to muscle building than to fat building. Combined with an appropriate diet, this leads to an overall shift in body composition away from fat deposition and toward muscle building and repair[6].

Learning and Memory

The GHS-R has been linked to learning and memory processes. Activating the receptor has been shown to increase long-term potentiation and dendritic spine density. Long-term potentiation is an increased in the strength of connections between neurons whereas dendritic spine density is a measure of how many connections are made between neurons. Ipamorelin, via its stimulation of the GHS-R improves both measures and thus has been shown to effectively improve mental functioning.

Ipamorelin Alters the Sleep Cycle

As a corollary to its effects on learning and memory, there is some evidence that Ipamorelin and other hGH boosters can have a beneficial impact on sleep[10]. Sleep is a critical arbiter of the learning process and is also a substantial factor in overall tissue age. Improved sleep has been shown to benefit concentration, learning, memory, mood, and general health. It is also associated with improved immune function and overall beneficial changes in body composition (e.g. muscle to fat ratio). In short, a peptide that promotes the effects of aging, even if it did nothing else, would be massively beneficial on a number of levels.

Ipamorelin Stimulates Increases in Bone Density

Current treatment for bone loss includes bisphosphonates, hormone therapy with parathyroid hormone, and new monoclonal antibodies. All of these are effective treatments, but come with potential side effects and high price tags. Ipamorelin may offer an alternative to these existing options that is easier to produce and thus less expensive. Peptides are simple products to make using widely available, safe, long-established principles of DNA recombination.

Bone loss is actually a two-part process consisting of increased bone degradation and decreased bone construction. Studies in rats show that ipamorelin is highly effective in stopping bone loss and that it increases bone formation by as much as 4-fold. Many of the drugs listed above act on only one of these mechanisms of bone degradation.

The benefits of Ipamorelin have been demonstrated in animal models of bone loss. In particular, glucocorticoid- (medical steroid) induced loss of bone may be particularly amenable to intervention with Ipamorelin. Additionally, the peptide’s protection against muscle may make it especially useful in bone loss associated with age. In rat studies, there was a 75% increase in total body bone mineral content with Ipamorelin before and after[2],[11-12].

Ipamorelin Cycle

Like many hormones, there is reason to believe that the body adapts to the presence of Ipamorelin over time, rendering the peptide less potent if used for too long. This is likely a consequence of changes in the density of ghrelin receptors (GHS-R). In fact, studies suggest that decreasing the concentration of ghrelin in natural systems leads to an increase in GHS-R activity over an approximately three-week timeframe. This occurs because the GHS-R is active even when nothing is bound to it.

The best way to think of the GHS-R is like a door. It its resting state, it is slightly open and thus encourages a little bit of hGH secretion. When ghrelin, or a peptide like Ipamorelin binds to the GHS-R, it is flung wide open and the secretion of hGH increases dramatically.

Over time, the body adapts to too much GHS-R activation by reducing the total number of GHS-Rs. As it turns out, the balance of this process is such that not stimulating the GHS-R for some period of time can lead to a large enough increase in GHS-R numbers that stimulation of GH actually increases over what is seen with moderate stimulation of the receptor. Thus, research has shown to get the most benefit out of peptide like Ipamorelin, it is important to cycle its application[13],[14]. A theoretical Ipamorelin cycle might look something like three weeks on and three weeks off. The three-weeks off would give the GHS-R population a chance to recover so that during the next three-week on cycle, the benefits of Ipamorelin would be even greater. This is one aspect of Ipamorelin usage that needs to be explored further in animal studies. With appropriate research, the best Ipamorelin cycles for muscle building, bone building, appetite control, and more can be determined.

Ipamorelin Fights Pain

All of the ghrelin mimetics have been shown to help to reduce both inflammatory and neuropathic pain to a variety of degrees. Recently, Ipamorelin has been shown to help to reduce visceral and somatic hypersensitivity, making it potentially useful in the treatment of hard-to-control GI and other visceral pain[15]. According to Dr. Beverley Greenwood-Van Meerveld, the director of the Oklahoma Center for Neuroscience, treating visceral pain effectively may also help to manage anxiety as the two phenomena may be related. The ability to control one may shed light on the mechanisms that cause the other. Ipamorelin offers an excellent means of exploring this dichotomy as it is well known to affect GHS-Rs in both the central nervous system and the peripheral tissue. The ability to treat visceral pain may also help doctors manage chronic, debilitating pain.

Ipamorelin Onset of Action

Depending on the research in question, the effects of Ipamorelin may be seen within hours or it may take months. For instance, research looking at blood glucose levels and circulating insulin concentrations will show results within minutes of Ipamorelin administration. Research investigating the effects of Ipamorelin on synaptic density, muscle mass, or bone density will require weeks or even months. Though Ipamorelin begins to have an immediate effect on the biochemistry of the body, the impacts of changing that biochemistry may not be seen for some time depending on how slow the particular pathway is. Building neurons, for instance, is a slow process. Thus, even though Ipamorelin has an effect on dendrite growth right away, the full extent of those effects will not be seen until the slow process of dendrite growth is complete. Experiments will need to take into account the rate of change that a particular biological system is capable of sustaining in order to estimate how long a period of time is required in order to judge whether the experiment was successful or not.

Ipamorelin Synergistic Effects

Ipamorelin may be synergistic with a number of hormones. Other GHS-R agonists, like Hexarelin and ghrelin, are generally synergistic with Ipamorelin. In addition, peptides that bind to the growth hormone releasing hormone receptor, such as CJC-1295, can act synergistically with Ipamorelin to dramatically increase growth hormone levels[16-18]. This latter effect is of interest to researchers in fields as diverse as tissue regeneration, anti-aging, and endocrine dysfunction.

Ipamorelin Drawbacks

Unlike other GHS-R agonists, Ipamorelin has no obvious drawbacks in animal studies. Perhaps the biggest drawback, if it can be called that, is that Ipamorelin must be administered via SubQ injection. There is currently no orally active form of the peptide. This can make administration of Ipamorelin, particularly in small animal studies, challenging. Overall, the peptide has demonstrated a robust safety profile and relatively minor side effects in the majority of studies.

Ipamorelin Before and After

For the majority of animals used in Ipamorelin research, Ipamorelin has a net anti-aging effect. Animals given Ipamorelin tend to demonstrate increased lean body mass, decreased fat mass, improved memory and cognitive function (particularly on spatial tasks), increased bone density, and overall increased levels of energy. In most animal studies, before Ipamorelin body composition tends to be what might be described as “soft.” The animals have higher fat mass and tend to be more lethargic. After Ipamorelin administration, animals tend to have a lean, hard look and are more active. This tends to be true in studies even when the investigative aim is to explore bone density or some other aspect of ipamorelin action. Ipamorelin before and after comparisons are similar to before and after comparisons following prolonged exercise. This should not be particularly surprising given that many of the benefits of exercise are mimicked by ipamorelin and vice versa.

Ipamorelin Structure


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Beverley Greenwood-Van Meerveld, Ph.D. – https://medicine.ouhsc.edu/Academic-Departments/Ph…

[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] Cао ЈЈ, Wrоnѕkі ТЈ, Іwаnіес U. “Аgіng іnсrеаѕеѕ ѕtrоmаl/оѕtеоblаѕtіс сеll-іnduсеd оѕtеосlаѕtоgеnеѕіѕ аnd аltеrѕ thе оѕtеосlаѕt рrесurѕоr рооl іn thе mоuѕе.” Ј Воnе Міnеr Rеѕ. 2005 Ѕер;20(9):1659-68.[3]N. K. Aagaard et al., “Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats,” Growth Horm. IGF Res. Off. J. Growth Horm. Res. Soc. Int. IGF Res. Soc., vol. 19, no. 5, pp. 426–431, Oct. 2009.[4]“Why does HGH decline with Age? – Cambridgewellbeing.org | The Well-Being Institute.” https://www.cambridgewellbeing.org/growth-hormone-… (accessed Nov. 14, 2020).[5]“Aging changes in hormone production: MedlinePlus Medical Encyclopedia.” https://medlineplus.gov/ency/article/004000.htm (accessed Nov. 14, 2020).[6]E. Adeghate and A. S. Ponery, “Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats,” Neuro Endocrinol. Lett., vol. 25, no. 6, pp. 403–406, Dec. 2004.[7]D. E. Beck, W. B. Sweeney, M. D. McCarter, and 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., vol. 29, no. 12, pp. 1527–1534, Dec. 2014.[8]B. Greenwood-Van Meerveld, K. Tyler, E. Mohammadi, and C. Pietra, “Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus,” J. Exp. Pharmacol., vol. 4, pp. 149–155, Oct. 2012.[9]M. M. Fowkes, T. Lalonde, L. Yu, S. Dhanvantari, M. S. Kovacs, and L. G. Luyt, “Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor,” Eur. J. Med. Chem., vol. 157, pp. 1500–1511, Sep. 2018.[10]A. Shimatsu, “[Ghrelin-related drugs: clinical perspectives],” Nihon Rinsho Jpn. J. Clin. Med., vol. 62 Suppl 9, pp. 435–438, Sep. 2004.[11]N. B. Andersen, K. Malmlöf, P. B. Johansen, T. T. Andreassen, G. Ørtoft, and H. Oxlund, “The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats,” Growth Horm. IGF Res. Off. J. Growth Horm. Res. Soc. Int. IGF Res. Soc., vol. 11, no. 5, pp. 266–272, Oct. 2001.[12]J. Svensson et al., “The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats,” J. Endocrinol., vol. 165, no. 3, pp. 569–577, Jun. 2000.[13]Y. Yin, Y. Li, and W. Zhang, “The Growth Hormone Secretagogue Receptor: Its Intracellular Signaling and Regulation,” Int. J. Mol. Sci., vol. 15, no. 3, Art. no. 3, Mar. 2014, doi: 10.3390/ijms15034837.[14]V. Martínez Damonte, S. S. Rodríguez, and J. Raingo, “Growth hormone secretagogue receptor constitutive activity impairs voltage-gated calcium channel-dependent inhibitory neurotransmission in hippocampal neurons,” J. Physiol., vol. 596, no. 22, pp. 5415–5428, 2018, doi: 10.1113/JP276256.[15]E. N Mohammadi, T. Louwies, C. Pietra, S. R. Northrup, and B. Greenwood-Van Meerveld, “Attenuation of Visceral and Somatic Nociception by Ghrelin Mimetics,” J. Exp. Pharmacol., vol. 12, pp. 267–274, 2020, doi: 10.2147/JEP.S249747.[16]M. Alba et al., “Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse,” Am. J. Physiol. Endocrinol. Metab., vol. 291, no. 6, pp. E1290-1294, Dec. 2006.[17]M. Ionescu and L. A. Frohman, “Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog,” J. Clin. Endocrinol. Metab., vol. 91, no. 12, pp. 4792–4797, Dec. 2006.[18]M. C. Van Hout and E. Hearne, “Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions,” Subst. Use Misuse, vol. 51, no. 1, pp. 73–84, Jan. 2016.
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