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Ipamorelin is a peptide that is widely used by athletes to increase performance and condition.
Effectiveness of ipamorelin is based on its activity as a growth hormone (GH) activator.
Stimulating the GH system endogenously by triggering release of the body’s own GH – in contrast to using external GH – has markedly fewer side effects as the body will not produce uncontrollable amounts of excess GH.
This makes peptides such as ipamorelin a safer, yet effective, alternative for use.
Ipamorelin may also provide a list of additional health benefits, including stronger bones, and a healthy digestive system.
What Is Ipamorelin?
Ipamorelin is a short synthetic peptide consisting of 5 amino acids (pentapeptide).
Similar to MK-677, ipamorelin acts as a ghrelin mimetic, promoting production and release of growth hormone (GH).
How Does Ipamorelin Work?
Ipamorelin mimics the GH releasing peptide (GHRP) ghrelin by binding to the GHRP receptors and activating GH release.
GH is produced in the pituitary gland, which oversees and regulates the endocrine system, responsible for hormone production and distribution.
The pituitary gland controls hormone levels of essential organs and body parts including the thyroid system, spleen, kidney, ovary, and testis, and – most importantly – activates longitudinal bone growth during childhood and adolescence.
Production of GH is controlled by regulating molecules such as GHRPs and hormones produced and secreted by the hypothalamus, located adjacent to the pituitary gland.
In contrast to other compounds that activate the pituitary GH system, such as GHRP-2 and -6, ipamorelin is more selective in its activation.
Activation of the GH system by ipamorelin by binding to its receptors results in the benefits of GH supplementation, such as increase in muscle mass and performance, without the potential side effects of GH therapy, such as increased risk of cancer.
An additional benefit of ipamorelin is that it is orally stable, in contrast to natural GHRPs such as ghrelin, and can be used orally or nasally, as well as being injected for direct use.
After nasal application, ipamorelin is transported through the nasal epithelium, the cell layer lining the inside of the nose, and approximately 20% of the used compound is available for use in the body (bioavailability). Ipamorelin is also metabolized slower than other GHRPs, making it more stable and thereby effective for longer.
Due to its effectiveness in stimulating performance, ipamorelin is listed on the World Anti-Doping Agency (WADA) prohibited list. It is readily detectable in the urine, even days after application.
While direct evidence for the benefits of ipamorelin is limited to animal studies and very few clinical studies in humans, benefits of this synthetic peptide can be expected to mirror those of ipamorelin’s biological relatives.
Ipamorelin for Growth & Bone Formation
As ipamorelin is a GHRP, its activation of GH should be expected to result in bone growth.
This has not been tested in humans, however, injection of different doses of ipamorelin into rats triggered longitudinal bone growth in a dose dependent manner – the more ipamorelin was injected, the quicker the bone grew over time. In addition, ipamorelin use also led to an increase in body weight. This study confirms the effectiveness of ipamorelin as a GH activator.
Other studies from the same researchers have shown that ipamorelin also increases bone mineral content in adult rats.
These findings show that ipamorelin maybe likely to support childhood growth, and keep bones strong and healthy during adult life and ageing.
Future studies are needed to confirm these assumptions.
Ipamorelin & Food Intake
The ghrelin system, and with it ghrelin mimetics and related molecules such as ipamorelin, are key regulators of eating behavior and food intake. The ghrelin system acts here as a “barometer” of the body’s energy household.
Ghrelin levels spike when the body needs more fuel in the form of food, and declines again after the demand has been satisfied.
Dysregulation of the ghrelin system in food-related disorders such as anorexia, as well as in obesity further adds to the evidence of the importance of ghrelin and its relatives for food intake and energy balance, and makes it a very interesting target to develop treatment approaches for these types of disorders.
However, so far the complexity of the system has delayed approval for treatment strategies using ghrelin-related peptides, but scientists are hopeful that these are on the doorstep.
Preliminary studies have shown that receptors that bind GHRPs are useful targets to treat people with malnutrition.
Ipamorelin may therefore be a suitable candidate to improve body weight and composition in malnourished or undernourished people.
An interesting side effect is that activation of the ghrelin system has also led to the improvement of hand grip strength here, most likely due to the improved body composition as well as due to an increase in circulating GH levels.
Ipamorelin for Constipation
Constipation is a chronic digestive condition that can seriously affect the quality of life. It affects up to a quarter of all people, and is becoming more prevalent. It may be associated with disorders such as irritable bowel syndrome (IBS) or other gastrointestinal disorders.
The GHRP ghrelin is present in the stomach and intestine, and has been shown to increase bowel activity in animal models. However, the problem of ghrelin is that it has limited stability and a short half-life.
Therefore, other GHRPs such as ipamorelin may be more attractive alternatives for treating constipation.
Constipation is particularly prevalent after intestinal surgery, and may lead to complications and weight loss.
Studies in rats have shown that use of ipamorelin after intestinal surgery leads to earlier bowel movements, compared to the control, as well as quicker recovery rates and weight gain.
Based on these outcomes, a proof-of-concept study investigated the effect of ipamorelin in humans after ileus surgery (bowel resection after occlusion). Constipation following ileus surgery can lead to complications and is currently difficult to manage.
Patients were given ipamorelin twice a day for 7 days post-surgery, and the time to the first solid meal was measured to assess bowel motion and appetite. Use of ipamorelin was well tolerated in these patients, and the time to the first solid meal was shorter than in the placebo group (25 hours vs 33 hours), however, the difference was not significant in this study.
A second human clinical study is currently underway that is still awaiting results. These preliminary findings indicate that ipamorelin may be a useful drug to improve patient outcome after bowel resection.
Future studies will likely investigate the effect of ipamorelin on more widespread disorders associated with constipation, such as IBS with constipation (IBS-C).
Ipamorelin & Bodybuilding
Ipamorelin is a compound that has enjoyed widespread use in the bodybuilding community, often in combination with CJC-1295. This is most likely due to its effective impact on increasing GH levels without triggering any of the potentially dangerous side effects of GH use.
The surge in GH plasma concentration following use of ipamorelin may result in the described benefits of GH on body composition. These include increased formation of muscle mass and increased muscle strength, increase in lean body mass, and improvements in performance.
The higher specificity of ipamorelin compared to related compounds may also lead to fewer side effects. Lack of activation of cortisol and other stress-related hormones, which may be associated with the use of other peptides and GHRPs, may make ipamorelin preferable to related agents.
Direct impact of ipamorelin on muscle strength and performance has been shown by its use to counteract steroid-induced decrease in bone formation in rats.
Here, rats had been treated with glucocorticoids, which act as anti-inflammatory and immunosuppressant drugs, and which cause bone deformation and muscle loss due to its catabolic effects. Treatment of these rats with ipamorelin resulted in increased and more rapid bone formation, as well as in an increase in muscle mass and strength.
Despite the diseases background of this animal model, these findings indicate that ipamorelin may have a role in muscle mass formation, and support muscle performance.
However, it has to be noted that ipamorelin is registered as a prohibited drug according to WADA regulations, and is therefore unsuitable to use before competitions.
Ipamorelin & Osteoporosis
Osteoporosis can become a problem for women after menopause, causing an increased risk of fractures and fragility.
While many factors are involved in the development of osteoporosis, hormones play a pivotal role, as they regulate both bone formation and breakdown.
Osteoblasts are cells that “make” bone, while osteoclasts are their counterparts – they break down bone cells. Both types of cells are essential for bone remodelling – during growth, repair and ageing. In addition, both cell types are needed to ensure adequate calcium and phosphate balance.
If the balance of osteoblasts and osteoclasts is disturbed, the effects may impact on bone growth and healing capacity, but also have further ripple effects on teeth, hair, nails, and nerve cells, due to the tipping of the delicate calcium and phosphate equilibrium.
The findings that ipamorelin increases the mineral formation of bones gives an indication of its use to keep bones strong and healthy during adult life, as well as to potentially counteract the development of osteoporosis.
Furthermore, GHRP-6, a peptide that is closely related to ipamorelin, activates osteoblasts and reduces the activity of osteoclasts in female rats. This may not only improve bone strength, but may also slow down the ageing process of bones, as osteoclasts become more active as we get older.
Ipamorelin may therefore be of specific benefit for women during ageing, to reduce the impact of age-mediated decline in bone strength.
Recommended dosage for off-label use is 200 to 300 µg per day, to be taken at the same time each day (preferably in the morning).
Ipamorelin Side Effects
The side effects of ipamorelin may include increase in appetite and weight gain, and nausea, but these may be transient. Further side effects may emerge from future clinical studies.
Ipamorelin is a short peptide ghrelin mimetic that is highly effective in stimulating GH release from the pituitary gland, harnessing the downstream benefits of GH activity, including increase in fat-free mass and muscle performance.
It activates hormone release with a much greater specificity than most other, similar compounds, thereby reducing the risk of side effects.
While evidence for benefits of ipamorelin in humans is still scarce, it has proven safe and well tolerated.
Based on evidence from animal studies and from related molecules, ipamorelin may play specific roles in preventing osteoporosis, during ageing, in digestive disorders, as well as in optimization of body composition and performance.