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Jul 8

Sermorelin vs Ipamorelin: Best Guide in 2022 – PeptideSciences.com

Sermorelin vs Ipamorelin

Sermorelin and ipamorelin peptides are very similar in many ways. Despite their similarities, however, these two peptides are different enough that their applications can be tailored for specific needs. Both peptides stimulate the natural secretion of growth hormone, but they do so via different receptors. As a result of their effects on growth hormone (GH) levels, Ipamorelin and Sermorelin both cause increased fat burning and muscle building, enhanced long bone growth, decreased inflammation, and improved wound healing. However, their actions via different receptors result in these two peptides having slightly different ancillary effects.

Sermorelin vs Ipamorelin: Receptor Science

Sermorelin is an analogue of growth hormone-releasing hormone (GHRH) and binds to the GHRH receptor (GHRH-R). Ipamorelin, however, is a ghrelin analogue and binds primarily to the growth hormone secretagogue receptor (GHS-R). While both peptides can be referred to under the umbrella category of growth hormone releasing peptides, their different receptor binding preferences mean they have different effects on GH levels.

At baseline, Sermorelin potentiates GH release and helps to extend GH highs. It is best thought of as extending GH peaks and prolonging the amount of time that GH levels are elevated while preserving the normal ebb and flow (pulsatile secretion) of GH throughout that day. Ipamorelin, on the other hand, is better thought of as dramatically raising GH levels, sometimes by as much as 13 times above baseline levels. Ipamorelin has dramatic, but short-lived effects on GH levels.

Sermorelin and Growth Hormone Potentiation

The GHRH-R is the primary receptor on the anterior pituitary gland for controlling growth hormone release. When stimulated, it causes the release of growth hormone. Research shows that Sermorelin binding to the GHRH-R is effective at concentrations as low as 0.4x10-15M[1]. This makes Sermorelin an extremely potent GHRH agonist and approximately 50 times more potent than naturally occurring GHRH. This is the reason that it was originally referred to as a super-active analogue of growth hormone releasing hormone[2].

Interestingly, Sermorelin tends to not cause massive increases in GH levels when it is administered. It does, however, augment the duration of GH release. That is to say, while Sermorelin definitely increases GH levels, its primary effect is to extend the duration of GH release, helping to maintain peak levels for longer periods of time[3]. By extending the release of GH, Sermorelin does, in fact, raise GH levels but it also smooths out the peaks of GH release and widens them a bit. This does not, however, obliterate the normal pulsatile secretion of GH, which is important for minimizing side effects. In fact, Sermorelins biggest benefit is the fact that it preservers the normal physiologic pattern of GH release, thus mitigating side effects like swelling, joint pain, and excessive long bone growth[4].

Ipamorelin and Growth Hormone Peaks

Ipamorelin (as well as ghrelin) is an amplifier of GH pulsatility and is speculated to play a role in creating a set point for insulin-like growth factor 1 levels[5]. Research has shown that subcutaneous administration of Ipamorelin causes an intense spike in growth hormone levels just 5-15 minutes after injection followed by a relatively rapid decline. Thus, ipamorelin does not really potentiate GH secretion like Sermorelin does. Instead, ipamorelin is better thought of as boosting maximum levels of growth hormone output for a very short duration of time. Depending on when and how ipamorelin is administered, this could mean augmenting peak GH levels or raising trough levels. Thus, timing of ipamorelin administration can, to some extent, affect the peptides effects.

Ipamorelin, at its ED50 (50% of the maximum effective dose), causes plasma GH levels to increase to approximately 65 ng/mL in animal models. Normally, growth hormone levels in men are below 5 ng/mL while in women they are below 10 ng/mL. This means Ipamorelin administration raises GH levels by anywhere from 6.5 to 13 times the maximum level. In children, growth hormone levels range from 0-20 ng/mL based on age. Ipamorelin has a short half-life of two hours. When administered, it causes maximum GH release after about 40 minutes followed by an exponential decline[6].

This rapid on, rapid off property of Ipamorelin is a holdover from its natural counterpart, ghrelin. Recall that ghrelin and Ipamorelin can both stimulate appetite. This occurs via binding to the GHS-R and subsequent release of neuropeptide Y. Given that it takes time to eat and digest food, it makes sense that ipamorelin would have its maximum effects approximately 40 minutes after injection (or release in the case of ghrelin). This gives the peptide its best chance of making using of nutrients for building muscle, bone, connections between neurons, and more.

Sermorelin vs Ipamorelin: Structure and Route of Administration

Sermorelin is made up of the first 29 amino acids from the much larger, naturally occurring GHRH peptide. It is the smallest fraction of GHRH than retains all of the properties of the parent molecule. Weighing in at 3357.9 g/mol, Sermorelin is a relatively large, heavy peptide that must be injected sub-cutaneous to be absorbed. It is not orally bioavailable. As a result of its large size, Sermorelin has a more significant three-dimensional structure than Ipamorelin and is thus is a little less stable in terms of storage half-life.

Source: PubChem

Ipamorelin is substantially smaller than Sermorelin at just5 amino acids and 711.868 g/mol. It is a derivative of GHRP-1, which is itselfa derivative of met-enkephalin. Though the most common route of administrationfor Ipamorelin is via sub-cutaneous injection, the peptide is also orallyactive and can even be absorbed though the nasal mucosa.

Source: PubChem

Ipamorelin vs Sermorelin: Lean Body Mass

Both Sermorelin and Ipamorelin favor the development of lean body mass over fat mass, but Sermorelin is the more potent of the two. This arises from the fact that Sermorelin is both a growth stimulator and a fat burner while Ipamorelin is a more general growth stimulator. That is not to say that Ipamorelin isnt effective, it is, but ipamorelin isnt as strictly favorable of lean body mass deposition as Sermorelin. This difference arises from the fact that Ipamorelin is a ghrelin analogue and ghrelin favors food intake in general. Its growth hormone boosting properties shift the overall balance away from fat deposition and toward lean body mass deposition, but the Ipamorelin peptide is best thought of as a general weight boosting peptide while Sermorelin is best thought of as a more exclusive booster of lean body mass. In fact, Sermorelin is often referred to as a lipolytic or fat-burning peptide.

Both peptides stimulate the development of bone and other connective tissue, but Ipamorelin appears to have the advantage in this realm. In fact, ipamorelin is so effective in boosting bone density and mineralization that it has been investigated as a potential treatment for corticosteroid-induced bone loss as well as osteoporosis[7], [8].

When it comes to muscle growth, Sermorelin is probably the big winner, though this can be debated endlessly. Sermorelin not only boosts muscle hypertrophy and hyperplasia, it reduces fat mass and thus causes a shift in body chemistry toward lean body weight. In other words, Sermorelin will always favor the production of lean body mass even if diet is not perfectly geared toward muscle development. Ipamorelin, on the other hand, is more of a mixed bag. It will always cause muscle growth, but ipamorelin may channel some of those calories into fat deposition as well.

Ipamorelin vs Sermorelin: Anti-Aging Properties

Both Ipamorelin and Sermorelin, via their GH releasing potential, have potent anti-aging properties. Sermorelin, however, is the clear front runner in this particular face off. Sermorelin has been shown to improve joint function, skin thickness, skin collagen structure, wound healing, cardiac fibrosis, strength, and metabolism. According to Dr. Richard Walker, Ph.D., of the International Society for Advanced Research in Aging, Sermorelin helps to preserve more of the growth hormone axis than most other GHRH analogues, resulting in a more youthful hormone profile. In other words, if you took profiles of GH biochemistry throughout an individuals lifetime, you would find that Sermorelin tends to dial back that chemistry to a more youthful setting.

Ipamorelin as Pain Reliever

One of the biggest differences between Ipamorelin and Sermorelin lies in the fact that Ipamorelin triggers the release of neuropeptide Y. This peptide is an important neurotransmitter in the control of appetite and food preference, but it also plays an important role in how we perceive pain. In fact, the connection between food and good feelings is likely due, in part, to the effects of neuropeptide Y.

Research in rats indicates that Ipamorelin may help to reduce pain perception by has much as 2-fold. This is particularly true of visceral pain, which is to say stomach pain. Visceral pain is difficult to treat, so ipamorelin offers a potential starting point for understanding how to better control the pain associated with conditions like irritable bowel syndrome, Crohns disease, ulcerative colitis, and more. There are also potential applications in neuropathic pain syndromes like diabetic neuropathy and degenerative disk disease[9].

Sermorelin and Sleep

Research in rats shows that Sermorelin is an effective regulator of the sleep cycle. Sleep and aging go hand int hand, with one affecting the other such that older people often have less adequate less restful sleep. Sermorelin appears to achieve its sleep benefits by regulating orexin release from specialized neurons in the brain. Orexin is an important neurotransmitter in sleep regulation and Sermorelin appears to boost orexin secretion. This leads to an increase in non-REM slow-wave sleep, which is associated with more restful sleep, improved immune function, better wound healing, and happier mood[10], [11]. Its effects on sleep may be one of the reasons that Sermorelin is a potent anti-aging peptide.

Sermorelin vs Ipamorelin: Summary

Sermorelin peptides and Ipamorelin peptides are more similar than they are different, but that doesnt mean there arent distinctions between these two growth-promoting peptides. Practically speaking, Sermorelin is the all-around peptide. It promotes lean body mass gains, boosts fat burning, and fights the effects of aging. It is also a more holistic simulator of the GH axis and, as such, helps the body to maintain youth-like patterns of GH secretion.

Ipamorelin is the more potent of the two peptides. Its effects are large, but relatively short-lived. Ipamorelin is a gainer peptide. It builds lean body mass, but also builds overall body mass. It is a potent stimulator of bone growth and has some pain fighting properties as well.

There has been some research investigating the effects of combining Sermorelin and Ipamorelin. Because these peptides affect two different receptors, their actions when combined tend to be synergistic. Unfortunately, the research in this area is limited, so there isnt a great deal of data on how the combination of these two peptides can help to improve appetite, alter body composition, fight off cardiovascular disease, slow the progression of aging, and promote general good health. In the end, both Ipamorelin and Sermorelin have been studied extensively, but individually, for their significant impacts on GH. Both peptides are effective, but have slightly different ancillary effects that have driven researchers in different directions as they explore potential applications for ipamorelin peptides and sermorelin peptides.

Resources

[1] M. L. Heiman, M. V. Nekola, W. A. Murphy, V. A. Lance, and D. H. Coy, An extremely sensitive in vitro model for elucidating structure-activity relationships of growth hormone-releasing factor analogs, Endocrinology, vol. 116, no. 1, pp. 410415, Jan. 1985, doi: 10.1210/endo-116-1-410.

[2] V. A. Lance, W. A. Murphy, J. Sueiras-Diaz, and D. H. Coy, Super-active analogs of growth hormone-releasing factor (1-29)-amide, Biochem. Biophys. Res. Commun., vol. 119, no. 1, pp. 265272, Feb. 1984, doi: 10.1016/0006-291x(84)91647-4.

[3] A. Grossman et al., Responses to analogues of growth hormone-releasing hormone in normal subjects, and in growth-hormone deficient children and young adults, Clin. Endocrinol. (Oxf.), vol. 21, no. 3, pp. 321330, Sep. 1984, doi: 10.1111/j.1365-2265.1984.tb03477.x.

[4] R. F. Walker, Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?, Clin. Interv. Aging, vol. 1, no. 4, pp. 307308, 2006, doi: 10.2147/ciia.2006.1.4.307.

[5] Y. Sun, P. Wang, H. Zheng, and R. G. Smith, Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor, Proc. Natl. Acad. Sci. U. S. A., vol. 101, no. 13, pp. 46794684, Mar. 2004, doi: 10.1073/pnas.0305930101.

[6] J. V. Gobburu, H. Agers, W. J. Jusko, and L. Ynddal, Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers, Pharm. Res., vol. 16, no. 9, pp. 14121416, Sep. 1999, doi: 10.1023/a:1018955126402.

[7] N. B. Andersen, K. Malmlf, P. B. Johansen, T. T. Andreassen, G. rtoft, and H. Oxlund, The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats, Growth Horm. IGF Res., vol. 11, no. 5, pp. 266272, Oct. 2001, doi: 10.1054/ghir.2001.0239.

[8] 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, pp. 56977, Jul. 2000.

[9] 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. 267274, 2020, doi: 10.2147/JEP.S249747.

[10] B. S. Shepherd et al., Endocrine and orexigenic actions of growth hormone secretagogues in rainbow trout (Oncorhynchus mykiss), Comp. Biochem. Physiol. A. Mol. Integr. Physiol., vol. 146, no. 3, pp. 390399, Mar. 2007, doi: 10.1016/j.cbpa.2006.11.004.

[11] A Good Nights Sleep, National Institute on Aging. http://www.nia.nih.gov/health/good-nights-sleep (accessed Nov. 22, 2020).

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Sermorelin vs Ipamorelin: Best Guide in 2022 - PeptideSciences.com

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