Sermorelin Acetate

Fifteen years ago, orexins were identified as central regulators of energy homeostasis. Research indicates that orexins are key modulators of the sleep-wake cycle and that these neuropeptides also affect feelings of satiety and hunger. Given their role in energy homeostasis, it was hypothesized that orexin levels are likely regulated, at least in part, by the growth hormone axis. Recent research supports this fact and suggests that growth hormone releasing hormone analogues, such as sermorelin, may be effective in treating conditions in which orexin release is dysfunctional (e.g. narcolepsy) [1].

Sermorelin Acetate and Aging

Growth hormone is a Goldilocks hormone, which is to say that it has an optimal level for producing the best outcomes. Too much GH increases morbidity and mortality, but so does too little. There is good evidence to suggest that at least part of the reason we age is because growth hormone levels decline over time, leaving us with sub-optimal levels of this important messenger. This decline in GH levels is referred to as somatopause and it has become a major focus of anti-aging science and research.

Somatopause is defined by the common symptoms we associate with aging: difficulty maintaining muscle mass, increased fat deposition, loss of bone density, declining energy and libido, higher cholesterol levels, and changes in skin texture and elasticity. Exercise helps to prevent these aging effects precisely because it keeps GH levels high, but more and more research suggests that exercise can only do so much to offset the roughly 40% decline in GH levels that occurs between the ages of 20 and 701. Supplementation may, in fact, be necessary to achieve optimal GH levels. This, ironically, increases exercise capacity, which makes it easier to maintain GH levels moving forward.

It was initially thought that Sermorelin and similar peptides simply reduced the effects of aging without actually prolonging life. For instance, Sermorelin improved muscle mass and body composition, but researchers thought it unlikely that the peptide could help us live longer. Research in mice, however, shows that Sermorelin, specifically, does improve longevity. The improvement is interesting however, as the research revealed a dramatic increase in average life expectancy but no change in maximum life expectancy2.

The above research is consistent with the idea that Sermorelin helps to maintain optimal body chemistry and thus maximizes lifespan. It does not extend maximum life expectancy, but it does help more individuals to get closer to their maximum lifespan. What is more, Sermorelin improves health and general function, meaning that individuals are more active and functional during their extended lives.

The benefits of Sermorelin in reducing the effects of aging include, but are not limited to:

• improved metabolism,
• improved body composition (more muscle and less fat),
• improved immune function,
• enhanced wound healing,
• better cardiac function, and
• improves sleep.

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 just 5 amino acids and 711.868 g/mol. It is a derivative of GHRP-1, which is itself a derivative of met-enkephalin. Though the most common route of administration for Ipamorelin is via sub-cutaneous injection, the peptide is also orally active 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 isn’t effective, it is, but ipamorelin isn’t 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.

Tesamorelin and Sermorelin are both synthetic growth hormone-releasing hormone (GHRH) analogues. Sermorelin is often used as a treatment for growth hormone deficiency in both children and adults. Sermorelin works by mimicking the action of the natural hormone, growth hormone-releasing hormone (GHRH), to increase the production of growth hormone in the body. This can have various benefits, including promoting growth in children, increasing muscle mass, reducing body fat, improving sleep, and enhancing overall well-being. Sermorelin is typically administered to individuals with growth hormone deficiencies or certain medical conditions.

Tesamorelin is used primarily to treat excess abdominal fat accumulation in people living with HIV/AIDS who have developed lipodystrophy. Lipodystrophy is a condition characterized by abnormal fat distribution in the body. Tesamorelin works by stimulating the pituitary gland to release growth hormone, which can help reduce visceral fat (fat stored in the abdominal area) in these individuals. It is administered through daily injections.

Both peptides are known for their ability to bring about changes in body composition, and both have been linked to improvements in heart health and cognitive function in mouse models. Despite their similarities, however, there are unique differences between these peptides. Understanding the subtleties that arise between these two very similar peptides is helping researchers to better understand physiologic pathways and develop better, more advanced therapeutics.

Tesamorelin vs Sermorelin | A Note on Growth Hormone

Researchers have shown interest in growth hormone (GH) therapy as an alternative approach to address body composition independently of the androgen-dependent gonadal axis. Studies have demonstrated that GH therapy can yield positive effects, including increased lean body mass, reduced adiposity, and improved serum lipid profiles. Despite these promising results, the use of GH therapy remains a subject of controversy and is subject to strict regulation. Potential side effects include joint stiffness, radiculopathy, edema, and a theoretically suggested but unproven increased risk of malignancy. The issue with direct GH supplementation is that it can easily lead to overdose. The body lacks a direct feedback mechanism for regulating GH levels and instead regulates the entire GH axis at the levels of synthesis and secretion. Given the benefits of GH, researchers began seeking alternative ways to stimulate GH release to avoid the potential problems associated with direct GH supplementation.

The result of these efforts was the development of a new class of peptides referred to as growth hormone secretagogues. Growth hormone secretagogue therapy has emerged as a promising substitute for GH therapy. These compounds exhibit numerous favorable effects similar to GH therapy but without the associated adverse side effects or regulatory issues. Growth hormone secretagogues stimulate the body’s own release of GH. This stimulation occurs either through direct mimicry of growth hormone release hormone (GHRH) or interactions with ghrelin/growth hormone secretagogue receptors (GHS-R), distinct from the conventional hypothalamic-pituitary-somatotropic axis. This article focuses on the growth hormone-releasing hormone (GHRH) analogues Tesamorelin and Sermorelin.

Research indicates that GHS treatment can elevate serum GH and IGF-1 levels to levels comparable to those achieved with recombinant GH therapy, resulting in similar reductions in fat and increases in lean muscle mass. Remarkably, specific GHS can uniquely induce the natural pulsatile secretion of GH observed in vivo. This stands in contrast to exogenous GH therapy, which often leads to sustained supraphysiological levels of GH in the bloodstream[1]. As a result, the administration of GHS has the potential to offer many of the same advantages traditionally associated with GH therapy while carrying substantially lower risks.

Sermorelin vs Ipamorelin and Tesamorelin

Sermorelin, Ipamorelin, and Tesamorelin are all peptides that stimulate the release of growth hormone (GH) in the body, but they have some differences in terms of their mechanisms of action and thus the overall effects that they cause. Sermorelin is a synthetic peptide that works by stimulating the secretion of growth hormone-releasing hormone (GHRH) from the hypothalamus. GHRH, in turn, triggers the release of growth hormone from the pituitary gland. Sermorelin is well known for extending growth hormone peaks and increasing growth hormone trough levels. It generally does not increase GH peaks, meaning it does not cause supraphysiologic levels of GH.Ipamorelin is a synthetic peptide that specifically targets the ghrelin/growth hormone secretagogue receptor. It stimulates the release of growth hormone directly from the pituitary gland. It is known for causing very large spikes in GH levels, well above normal physiologic peaks. It is a short-lived peptide, however, and so the GH spikes are short-lived as well.Tesamorelin is a synthetic peptide that is similar in structure to human growth hormone-releasing hormone (GHRH). It stimulates the release of growth hormone from the pituitary gland. Tesamorelin is used clinically for reducing adiposity (fat tissue) and is more similar to Sermorelin than it is to Ipamorelin. Like Sermorelin, it extends the length of time that GH peaks last, but does not generally cause supraphysiologic GH levels.Sermorelin and Tesamorelin are the most similar, but it would be mistake to conflate the properties of these two peptides. Despite the fact that both are GHRH analogues and thus stimulate the release of GH from the anterior pituitary, there are profound differences in overall outcomes produced by these peptides. Whereas Tesamorelin tends to produce weight loss via targeting of fat mass, Sermorelin tends to favor muscle building and balanced fat burning resulting in body composition change, but not necessarily a huge change in weight.These differences are just one example of how peptides from the same class can differ from one another based on simple structural changes made to their amino acid sequences. Researchers have, for years now, been investigating how these subtle changes influence target effects, half-life, off-target effects, bioavailability and other features of these peptides. Now, with enough different growth hormone regulators on the market, research is starting to shift to investigate how combinations of these peptides stack up to one another. Here is a look at how Sermorelin on its own might compare to a combination of Ipamorelin and Tesamorelin. 

Sermorelin vs Ipamorelin and Tesamorelin | Growth Hormone Profiles

The primary action of all of these peptides is to influence levels of circulating growth hormone. Tesamorelin and Sermorelin do this by acting on the GHRH receptor while Ipamorelin influences GH levels by acting on the ghrelin or growth hormone secretagogue receptor (GHS-R). The receptors that these peptides target in addition to how they bind to their specific receptors determines their impact on growth hormone levels.

Sermorelin is very similar in structure to GHRH and thus is similar in function as well. Research shows that Sermorelin can lead to an increase in GH with peak levels occurring about 30 minutes to a few hours after administration. On average, studies have reported GH increases in the range of 2 to 10 times the baseline GH levels following Sermorelin administration, with once-daily administration resulting in increases that are on the lower end of that spectrum. One of the benefits of using Sermorelin is that it promotes a natural, pulsatile release of GH. The body’s natural GH secretion occurs in a pulsatile fashion, with several peaks and troughs throughout the day. Sermorelin therapy aims to replicate this pattern, which is essential for the body’s overall growth and maintenance. Maintenance of pulsatile GH release is one of the primary keys to avoiding off-target effects.

Ipamorelin is a ghrelin mimetic and as such binds to the GHS-R. In clinical and research studies, Ipamorelin has been shown to increase GH levels, but the magnitude of the increase can vary. Typically, after the administration of Ipamorelin, there is a rapid spike in GH levels, and this peak can reach levels several times higher than baseline. Of the three peptides here, Ipamorelin is the most likely to cause massive, but short-lived increases in GH levels. This, of course, makes Ipamorelin useful when targeted GH peaks need to be timed with something like exercise, food intake, or sleep.

The increase in GH levels after Ipamorelin administration tends to be dose-dependent, meaning that higher doses are generally associated with a more significant GH response. The frequency and timing of Ipamorelin administration can also influence GH release. As a short-acting peptide, Ipamorelin can be dosed more frequently than Sermorelin to achieve net increases in GH levels. This is made possible not just by Ipamorelin’s short half-life, but by its near total lack of off-target effects. Ipamorelin is widely regarded in research circles as the most specific of the growth hormone secretagogues and as having the fewest off-target effects.

Tesamorelin is a GHRH analogue. Studies of Tesamorelin have shown that it can lead to an increase in growth hormone levels and this increase is generally within a physiologically normal range. The specific increase in GH levels can depend on factors such as the individual’s baseline GH levels, the dosage of Tesamorelin administered, and the duration of treatment. Like Sermorelin, Tesamorelin can help to preserve the normal pulsatile pattern of GH release from the pituitary gland, acting to extend the duration of GH peaks while having less effect on peak GH levels.