Peptides For Muscle Growth and Body Composition

Researchers interested in exploring the domain of peptides for muscle growth might be interested in the most potent compounds for this purpose.

Numerous therapeutic peptides have been correlated with benefits such as:

• Enhanced muscle growth
• Increased lean mass
• Better body composition
• Improved muscle strength

To assist our readers, we have consolidated the most recent clinical findings to produce this detailed guide on peptides for muscle growth and body composition improvement.

In this comprehensive overview, researchers will become acquainted with the most effective peptides for muscle growth, detailing their mechanisms of action, efficacy, safety parameters, and potential adverse effects.

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Top 3 Peptides For Muscle Growth

Before we delve into the science of peptides for muscle growth, let’s go over three peptides that stand out among the most researched and effective compounds in the field.

1. Sermorelin

Sermorelin is the shortest functional peptide that can stimulate the receptors of growth hormone-releasing hormone (GHRH) to produce growth hormone (GH). GH is an anabolic hormone, and by increasing it, sermorelin has been noted to improve growth in children, for which it held regulatory approval. Likewise, it has been found to increase lean body mass and potentially muscle growth in adults after four months of administration [1].

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2. MK-677

MK-677 (ibutamoren) is an orally active non-peptide compound that works similarly to peptide-based growth hormone secretagogues (GHSs) that mimic the endogenous hormone ghrelin. It is investigated as a potential therapy for growth failure and GH deficiency. Still, studies also report that it can increase lean mass and muscle growth. Trials report a +6.6lb increase in lean body mass after two months of administration [2].

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3. Tesamorelin

Tesamorelin is a peptide that stimulates GH release via the GHRH receptors and is approved for reducing abnormal body fat distribution in patients with HIV/AIDS. Studies have shown that tesamorelin helps these patients avoid significant losses of muscle mass by increasing muscle density and size [3].

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What are Peptides?

Peptides are molecules made of amino acids chained together by peptide bonds. This yields intricate molecular structures with properties dictated by their distinct amino acid sequences.

Peptides typically range between 2-50 amino acids in length and can be considered small proteins [4].

They actively participate in numerous physiological processes, including as vital cellular communicators, hormone modulators, and growth regulators, thus drawing interest from the scientific community [5].

This has led to the development of therapeutic peptides, which are synthetically constructed amino acid sequences that often resemble their natural counterparts.

Yet, synthetic peptides frequently undergo strategic modifications compared to their physiological analogs for enhanced efficacy, selectivity, pharmacokinetics, and safety.

Presently, over 60 peptide-derived pharmaceuticals have received approval for human administration, while hundreds more are currently under rigorous investigative study [6, 7].

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How Do Peptides Work For Muscle Growth?

Several research peptides have shown significant potential for enhancing muscle mass and strength.

One primary mechanism through which certain peptides may foster muscle growth is by upregulating the production and secretion of GH, which subsequently influences the expression of insulin-like growth factor-1 (IGF-1).

IGF-1 is the main anabolic mediator of GH and is mostly produced in the liver under the effects of GH and then released into the circulation. In addition, GH can also stimulate the synthesis of IGF-1 directly inside muscle tissue in a paracrine or autocrine manner.

Studies report that IGF-1 can stimulate muscle anabolism by both increasing muscle protein synthesis (MPS) and reducing muscle protein breakdown (MPB) [8]:

• MPS may be upregulated primarily via the phospholipase B/mTOR pathway, which is the main anabolic pathway in muscle cells.
• MPB may be downregulated by inhibiting the signaling of several catabolic mediators, including myostatin, a protein that is a major suppressor of muscle growth.

In addition, certain peptides may work by interacting directly with muscle growth regulators/inhibitors. For example, the peptide follistatin 344 is under research for its potential to inhibit myostatin and prevent its limiting effects on muscle growth [9].

Yet, further study is warranted to fully comprehend and confirm the interactions of peptides such as myostatin inhibitors within the human body.

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Does Peptide Therapy for Muscle Growth *Actually* Work?

Peptides have shown significant potential for increasing GH, consequently resulting in increased IGF-1 levels and muscle growth. Currently, two related groups of peptides achieve this:

• Growth hormone-releasing hormone (GHRH) analogs can increase GH/IGF-1 levels by mimicking the function of endogenous GHRH, the main physiological regulator of GH synthesis [10].
• Growth hormone secretagogue receptor (GHS-R) agonists can also increase GH/IGF-1 as they activate the ghrelin receptors in the pituitary gland but also in other parts of the body. These pituitary receptors are also called the GHS receptors, and activating them triggers GH synthesis [11].

GHRH analogs like tesamorelin, sermorelin, and CJC-1295 have demonstrated their ability to elevate GH/IGF-1 levels and increase muscle mass in clinical settings:

• Sermorelin, administered at 10mcg/kg/daily for up to 16 weeks in elderly subjects, led to an increase in GH levels by a mean of 107% and IGF-1 levels by a mean of 28% in male participants. There was also an increase of +2.78lb (+1.26kg) in lean mass in the male group[1].
• Tesamorelin, administered at 2mg/daily for two weeks, was reported to cause a 69% increase in total GH levels (area under the curve – AUC) and a 55% increase in the mean pulse area in 13 middle-aged male subjects [12].
• CJC-1295, applied as a single injection in healthy men aged 20-40, increased basal GH levels by 7.5-fold, contributing to an overall increase in GH secretion by 46% and IGF-I levels by 45% [13].

GHS-R agonists like ipamorelin and MK-677 (ibutamoren) have also shown great promise for increasing GH/IGF-1 levels and muscle growth:

• MK-677, administered as 25mg/daily capsules, increased mean 24-h GH concentration by 97% and IGF-1 levels by 88% after 4 weeks of therapy in healthy elderly subjects. Pulsatile GH-release also increased 1.7-fold over 24 hours [14]. Another 8-week study with the same dose in obese subjects reported a +6.6lb increase in lean body mass without affecting fat mass compared to placebo [2].
• Ipamorelin, administered to healthy human volunteers at a single dose of 77mcg/kg, led to a spike in GH that reached 26.6ng/l [15].

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Best Peptides For Muscle Growth and Body Composition

Peptides can play a pivotal role in supporting muscle growth, enhancing performance, and fostering recovery.

As we delve into the topic of peptides for muscle growth, we'll navigate through the most researched peptides in this domain, elucidating their distinct features, roles, and the scientific data backing their efficacy.

Here are the best peptides for muscle growth:

Sermorelin

Sermorelin, or GRF 1-29, is a synthetic analog of growth hormone-releasing hormone (GHRH) developed by EMD Serono for growth hormone (GH) stimulation [16].

While physiological GHRH comprises 44 amino acids, only the first 29 are crucial for pituitary receptor binding and GH release; sermorelin replicates these 29 amino acids, making it the shortest functional GHRH analog [17].

The peptide was approved by the United States Food and Drug Administration (FDA) for diagnostic and therapeutic purposes in growth hormone deficiency. Still, the approval was withdrawn at EMD Serono's request for commercial rather than safety or effectiveness reasons [18].

Sermorelin continues to be researched for a variety of uses, such as muscle growth:

• Research indicates sermorelin's potential for muscle enhancement. A study in elderly males reported a notable +2.78lb lean body weight increase after administration of 10mcg/kg as a once-daily subcutaneous injection for 16 weeks [1].
• Some studies have also shown great potential with twice-daily administration, which some authors favor due to the short 10-minute half-life of sermorelin [19].

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MK-677

MK-677, also known as ibutamoren, is a GHS with a non-peptide structure that functions similarly to growth hormone-releasing peptide-6 (GHRP-6) [20].

It was developed in the 1990s by Merck & Co to target growth hormone deficiency (GHD). Presently, Lumos Pharma is evaluating MK-677 in phase 2 trials for children with GHD [21, 22].

Thanks to its non-peptide structure, MK-677 has 60%+ oral bioavailability. It also possesses a half-life of 4-6 hours, and single daily oral intake can significantly increase GH and IGF-1 levels [23, 24].

Oral ingestion of MK-677 activates the pituitary gland's GHS receptors by crossing the blood-brain barrier, promoting GH release. Clinical studies show that MK-677 significantly raises GH and IGF-1 levels while marginally elevating cortisol and prolactin:

• In a study in young obese participants, MK-677 taken at the dose of 25mg/daily over 8 weeks resulted in a +6.6lb lean body mass gain without affecting fat mass [2].
• Clinical research has also highlighted that MK-677 reduces nitrogen losses and prevents muscle loss during calorie restriction [25].

As of writing, MK-677 lacks approval from the FDA and is categorized as an Investigational New Drug, available strictly for academic or experimental purposes [26].

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Tesamorelin

Tesamorelin is a synthetic analog of growth hormone-releasing Hormone (GHRH), enhanced by a trans-3-hexenoic acid group that amplifies its potency and stability [27]. It has a half-life of 30-40 minutes, and peaks in concentration within 30-60 minutes from administration [12, 28].

Developed by Theratechnologies, this peptide specifically addresses lipodystrophy in HIV/AIDS patients through upregulation of GH, which is known to reduce excess abdominal and visceral fat [29]. As a result of its efficacy, the peptide gained FDA approval in 2010 under brand names Egrifta and Egrifta SV [30, 31].

Tesamorelin is also under active research for other indications related to improving body composition, such as muscle-building and lean mass increase.

For example, one study reported that tesamorelin, at a daily dosage of 2mg, significantly mitigated muscle wasting in HIV/AIDS patients after 26 weeks of treatment. It also significantly increased muscle density and size at various body sites of the participants [3].

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Ipamorelin

Ipamorelin is a pentapeptide formulated by Novo Nordisk and Helsinn Therapeutics. It was designed to replicate ghrelin's effects in the gastrointestinal tract to facilitate peristalsis [32, 33].

Empirical data reveal that ipamorelin notably augments growth hormone/insulin-like growth factor-1 (GH/IGF-1), exhibiting selectivity by not influencing other pituitary hormones. This specific activity persists for approximately 2-3 hours, aligning with ipamorelin's half-life of 2 hours [34].

Initial investigations indicate that the peptide not only elevates appetite and induces weight gain, but also shields against muscle waste in test animals, namely those subjected to catabolic agents [35, 36].

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CJC-1295

CJC-1295 DAC is a tetrasubstituted derivative of the peptide sermorelin that exhibits enhanced pharmacokinetic properties, extending its half-life from 10 to 30 minutes. Additionally, it is commonly modified with the integration of a drug affinity complex (DAC) that prolongs its half-life by binding to plasma proteins, further extending it to eight days [37, 38, 39].

Originally developed by the Canadian biotechnology firm ConjuChem, CJC-1295 DAC aimed to address lipodystrophy in HIV/AIDS patients. The peptide is able to continuously activate the GHRH receptors, leading to enhanced growth hormone (GH) pulse frequency.

For example, a study in 29 men documented elevated GH synthesis for over six days following a single administration of CJC-1295 and identified a cumulative effect upon repeated dosing. Likewise, a single injection led to sustained elevation of IGF-1 levels for a fortnight [40].

Although the peptide has not been researched for its muscle-building properties, its ability to increase IGF-1 is expected to have significant anabolic effects on muscle tissue.

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Follistatin 344

Follistatin-344 (FS-344) is a peptide-based compound made of 344 amino acids that is known to inhibit myostatin. The latter is a protein that is responsible for regulating and limiting muscle growth.

By blocking myostatin, follistatin-344 leads to an increase in muscle mass, which has been observed in laboratory animal studies employing gene therapy with the peptide [9].

Preliminary clinical studies in subjects with muscular dystrophy have also shown that the peptide improved muscle strength without any notable side effects. FS-344 was specifically tested in patients with Becker muscular dystrophy (BMD)—a genetic disease that results in progressive muscle degeneration and weakness [41].

Yet, case studies in individuals using FS-344 for performance enhancement suggest that its use may be associated with significant risks, including central serous chorioretinopathy (CSCR) [42].

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Hexarelin

Hexarelin (aka examorelin, EP-23905 and MF-6003) is another GH secretagogue that triggers the ghrelin receptors to stimulate the release of GH and its anabolic metabolite IGF-1.

Studies in healthy volunteers suggest that when administered before sleep, the peptide can induce a significant increase in GH levels, and that such elevation is greater compared to other peptides and hormones such as GHRH and GHRP-6 [43].

Notably, the researchers have also noted that hexarelin elevated the subjects’ prolactin levels throughout the whole night, and increased ACTH and cortisol levels during the first half of the night [24, 43].

Studies in children with short stature also report that hexarelin stimulates linear growth and spurs weight gain in proportion to the height increase in the tested subjects [44].

Interestingly, animal studies with hexarelin report a 3.3% increase in lean mass and a 13% decrease in body fat, which is in contrast with the total weight gain reported by studies in other GHSs [45].

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GHRP-6

GHRP-6 is the first clinically studied GH secretagogue. It has low oral bioavailability with a half-life of 2-3 hours, and activates both the ghrelin receptors and the CD36 receptors [23].

By activating the ghrelin receptors, the peptide stimulates both GH and hunger levels. The combination of increased GH levels, consequently elevated IGF-1 levels, and increased food intake can contribute to significant weight gain, potentially attributable to increased muscle mass [23].

In addition, its activation of the CD36 receptor may mediate some benefits for tissue recovery and regeneration [46].

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IGF-1-LR3

IGF-1 LR3, also known as Long R3 IGF-1, is a synthetic version of IGF-1, which plays a key role in muscle and tissue growth. This modified peptide is designed for increased effectiveness and stability compared to standard IGF-1.

The “Long” in Long R3 IGF-1 comes from the addition of 13 amino acids to the IGF-1 molecule, which enhances its activity. “R3” refers to the replacement of the third amino acid in IGF-1 with arginine, a change that boosts the hormone's anabolic, or muscle-building, effects.

Animal studies have shown that IGF-1 LR3 binds more effectively to anabolic IGF-1 receptors. When given continuously, IGF-1 LR3 demonstrated up to twice the muscle-building effects of regular IGF-1. This was evidenced by increased weight gain and organ weight in the tested animals [47].

When it comes to pharmacokinetics, research in mice has found that IGF-1 LR3 is completely eliminated from the body within four hours of an intramuscular injection, suggesting a half-life of less than one hour. However, its metabolites were detectable for up to 16 hours after injection [48]. Additionally, animal research indicates that IGF-1 LR3 may help protect against muscle loss and breakdown, making it a potential candidate for preserving muscle mass in various conditions [49].

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Peptides Side Effects and Safety

The growth hormone secretagogues listed above appear to have favorable safety profiles, exhibiting only mild, transitory side due to the increase in GH levels.

Nevertheless, it should be noted that the majority of these compounds are not approved for human use, so researchers should be cautious when incorporating them in their experiments.

Researchers should also note that GH secretagogues are contraindicated in subjects with a history of cancer or active malignancies, as the increase in GH and IGF-1 levels can stimulate the proliferation of cancer cells and disease progression.

Below, we outline the main side effects reported by clinical data for each of the aforementioned peptides:

• MK-677

Studies suggest that the compound can lead to mild, transitory side effects, including [43]:

– Increased hunger (67%)
– Arthralgia (58%)
– Edema of the limbs (44%)
– Myalgia (33%)

Doses higher than 25mg/daily have also been associated with skin dryness and diarrhea [44].

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• Tesamorelin

Phase 3 trials reveal that the peptide can cause the following side effects [45]:

– Injection site reactions (24.5%)
– Edemas on limbs (6.1%)
– Insulin resistance (4.5%)

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• CJC-1295

Studies report mild to moderate side effects, including [40]:

– Injection site reactions
– Headaches
– Diarrhea
– Nausea
– Abdominal pain
– Flushing

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• Sermorelin

Studies in adults have not reported any side effects, except for a case of transient hyperlipidemia in one patient, according to a 16-week study [1].

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• Ipamorelin

Human studies lasting up to one week do not report any side effects associated with the peptide [32]. Yet, longer trials will likely have side effects similar to MK-677, such as increased appetite levels and potentially edema.

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Do Peptides Work Like Steroids Would?

While both peptides and anabolic-androgenic steroids (AASs) can result in a significant increase in lean mass, there are significant differences between the two groups of compounds, including how they work, their safety profiles, and their efficacy.

Below, we provide a comprehensive comparison between peptides and AASs:

• Mechanisms of action: Peptides do not work like AASs as they do not affect the steroid receptors found in the nuclei of muscle cells. Thus, unlike AASs, peptides cannot push muscle growth beyond its genetic potential [46]. Instead, peptides typically drive muscle growth by upregulating the endogenous production of hormones like GH and IGF-1.
• Risks and side effects: Both classes of compounds have specific risks and side effects. Yet, peptides are generally considered safer than AAAs due to their targeted mechanisms of action and the lower risk of causing endocrine imbalances. In comparison, AASs have broad effects, which often affect tissues other than muscles. AASs have been reported to cause gynecomastia, elevated risk of thrombosis, worsened lipid profile, psychological changes, infertility, and more. Many oral AASs may also lead to liver damage [47, 48, 49, 50, 51].
• Effectiveness for muscle growth: As noted, GH secretagogues like MK-677 have been reported to cause up to +6.6lb lean body mass gain within 8 weeks [2]. On the other hand, AASs are much more potent for boosting muscle protein synthesis and muscle growth. Studies involving high-dose therapy with testosterone enanthate for 10 weeks report a mean +13.2lb increase in muscle mass [52]. Research in AASs reports significant increases in muscle mass even during severely restricted dieting and low energy intake [53].

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Other Risks With Muscle Growth Peptides

Researchers should also consider other disadvantages and caveats with research peptides for muscle growth and body composition, related to their legal status, potential undesired properties, and effectiveness:

• GHSs may lead to total weight gain rather than just lean mass increase: Peptides like MK-677 and ipamorelin work by activating the ghrelin receptors, which, apart from stimulating GH/IGF-1 increase, may also lead to an increase in hunger.
  While some researchers may aim at investigating the potential of these peptides for total weight gain, including both fat and muscle mass, those who want to target only lean muscle may prefer focusing their research on GHRH analogs [23].

• Peptides for muscle growth are generally banned by WADA and considered illegal in sports: All of the peptides on our list are banned by the World Anti-Doping Agency (WADA) under the category S2: peptide hormones, growth factors, related substances, and mimetics. This means that these compounds are prohibited both during and outside of competition subject to the WADA Code and related rules [54].
• Peptides for muscle growth may have limited effects under certain conditions: While increasing GH/IGF-1 levels has well-known anabolic effects, some subjects may experience suboptimal results when peptides are not used alongside a proper dietary and exercise regime. Therefore, scientists are recommended to combine peptide therapy with appropriate lifestyle changes into their protocols for muscle growth research.

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Peptides and Muscles | Verdict

Compounds such as tesamorelin, sermorelin, MK-677, ipamorelin, CJC-1295, and follistatin-344 have been shown in preclinical and clinical research to increase muscle mass, lean body mass, and muscle strength.

The available scientific research also suggests that the majority of these compounds have favorable safety profiles, although many of them are yet to be approved for human use.

Scientists conducting research on the implications of peptides for muscle growth are highly advised to obtain their reference materials from a reliable source.

We recommend checking out our top recommended vendor for sourcing research-grade peptides for educational or experimental use.

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