What is MK-677?
MK-677 (ibutamoren) is classed as a non-peptide spiroindoline and spiropiperidine. Yet, it functions in a manner akin to a peptide called growth hormone-releasing peptide-6 (GHRP-6) [1].
Here is what researchers should know about the structure and function of MK-677 [2]:
- Similar to GHRP-6, MK-677 is designed to cross the blood-brain barrier and activate receptors of the ghrelin hormone in the pituitary gland, prompting the release of growth hormone (GH). Thus, it is classified as a growth hormone secretagogue (GHSs).
- Unlike peptide-based GHSs, MK-677’s non-peptide structure gives it oral bioavailability exceeding 60%, allowing it to be administered in an oral form instead of injections.
It was developed in the 1990s by Merck & Co, who sought precisely to create a GHS that could be taken orally but which nonetheless could be useful in treating growth hormone deficiency (GHD) [3].
Lumos Pharma, a company focusing on rare disease treatments, is currently investigating MK-677 in phase-2 clinical trials to evaluate its efficacy in treating childhood-onset GHD [4].
Overall, this GHS appears to have great efficacy and a favorable safety profile. Studies have shown that MK-677 leads to notable increases in GH and insulin-like growth factor 1 (IGF-1) levels while only temporarily raising the levels of hormones like cortisol and prolactin.
When administered orally, MK-677 has a half-life of about 4-6 hours, and it has shown potential benefits such as [2, 5]:
- Enhancing muscle mass
- Improving sleep quality
- Lowering cholesterol levels
MK-677 is still under active research and has not yet been approved by the United States Food and Drug Administration FDA for human use. It is classified as an Investigational New Drug and is available for purchase by qualified professionals for research or educational purposes [6].
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What is Sermorelin?
Sermorelin, also called growth hormone-releasing factor 1-29 (GRF 1-29), is a synthetic peptide mirroring the initial 29 amino acids of endogenous growth hormone-releasing hormone (GHRH) [7].
Sermorelin also mimics the primary function of GHRH, which is to directly stimulate the GHRH receptors in the pituitary gland and induce GH synthesis [8].
Here is what researchers should know about sermorelin:
- Developed in the 1980s by EMD Serono, sermorelin is a truncated yet fully functional version of GHRH’s 44 amino acid chain, prompting GH release [9].
- While shorter in structure, sermorelin exhibits a comparable half-life to GHRH, which is about 10 minutes following injection [10].
- Initially marketed as Geref by EMD Serono, it was FDA-approved as a stimulation test for GHD diagnosis in 1990 and for therapy in children with short stature in 1997 [11].
- In 2008, the FDA withdrew its approval of Geref at the request of EMD Serono. The withdrawal was for commercial reasons and not due to safety or efficacy concerns [11].
Sermorelin is now actively studied in research settings for its growth hormone-increasing potential.
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MK-677 vs. Sermorelin | Comprehensive Comparison
While the two may have some similar effects, MK-677 and sermorelin have vastly different structures and mechanisms.
MK-677 is a non-peptide growth hormone secretagogue with affinity to the ghrelin receptors, while sermorelin is a peptide agonist of the GHRH receptors of the pituitary gland.
Both compounds are highly effective at increasing GH and related hormones, including IGF-1, which is growth hormone’s main anabolic mediator.
Here is what researchers should know about the impact of sermorelin administration on GH and IGF-1 secretion.
- In a study in elderly individuals, sermorelin was reported to cause up to a 107% increase in mean 24-hour GH levels and a 28% increase in mean IGF-1 levels in treated men [12]. In another study in 11 elderly male participants, each receiving sermorelin 2mg/daily as a single subcutaneous injection, elevated GH concentrations remained for about two hours following each injection [13].
- Sermorelin has also been applied as twice-daily injections (morning and evening) at a dose of 1mg per shot. In a study in elderly men that applied this regimen, the researchers reported a 64% increase in the participants’ mean 24-hour GH levels, with a higher increase after the evening injection [14].
Similarly, clinical testing of MK-677 has shown impressive increases in GH and IGF-1 levels, even after a single administration:
- A study in eight healthy volunteers, each given a single 25mg MK-677 dose combined with caloric restriction, reported that the GHS led to a dramatic 55.9ng/ml peak in GH levels [15]. As a reference, physiological GH peaks are within the range of 10-14ng/ml.
- A trial in 32 healthy older adults reported that MK-677 at 25mg/daily increased the mean 24h GH concentration by 97%, while pulsatile GH release increased by 1.7-fold. Moreover, daily administration led to a 55% increase in IGF-1 levels at two weeks and 88% at four weeks [16].
Given these similarities and differences between MK-677 and sermorelin, let’s now delve deeper into the findings of key clinical studies involving both compounds.
Research Applications and Benefits of MK-677
Numerous studies have explored the effects of MK-677 on human health and the benefits related to the significant boost in GH post-administration.
Apart from stimulating the ghrelin receptors of the pituitary gland, MK-677 also acts on other ghrelin receptors in the brain, which may influence appetite levels and sleep quality [17].
Due to its appetite-stimulating effects, MK-677 is not expected to induce fat loss despite the well-known fat-burning properties of elevated GH.
Here’s a summary of key research findings involving this orally active GHS:
- Increased Muscle Growth and Lean Mass: In an 8-week study in 24 overweight young adults, where MK-677 was administered at a dose of 25mg/daily, the researchers observed an increase of +6.6lb in lean body mass without impacting the volunteers’ fat mass [18].
- Reduced Muscle Wasting: Another study in eight healthy subjects highlighted the compound’s ability to significantly decrease nitrogen loss, particularly when following a calorie-restricted diet [15].
- Lower LDL Cholesterol: In a two-year study in 65 elderly volunteers, the daily administration of MK-677 at the dose of 25mg was found to markedly reduce low-density lipoprotein (LDL) cholesterol—or “bad cholesterol.” While the placebo group had a 0.12mmol/l increase in LDL, the MK-677 group saw a decrease of 0.14mmol/l within the first year of the study [19].
- Enhanced Sleep Quality: In a two-week study in eight participants, daily administration of MK-677 at the dose of 25mg led to an increase in deep sleep duration by around 50%, and a 20%+ increase in rapid-eye movement (REM) sleep [20].
Research Applications and Benefits of Sermorelin
Sermorelin has been shown to effectively boost the production of GH and its anabolic mediator IGF-1.
The longest sermorelin clinical study to date spanned 16 weeks and involved 19 elderly individuals who were given 10mcg/kg of sermorelin daily.
Key findings from the study included [12]:
- Increased Lean Body Mass: The male study participants had an average lean mass increase of +2.78lb. However, the female participants did not show similar gains. Despite this discrepancy, enhanced nitrogen retention was noted in both sexes, highlighting the anabolic capabilities of sermorelin.
- Enhanced Skin Thickness: Both the men and women had increased skin thickness, suggesting that the rise in GH also led to an increased activity of collagen-producing skin cells, such as fibroblasts.
Unfortunately, no clinical study to date has confirmed any significant impact on fat mass as a result of sermorelin administration. Yet, sermorelin is posited to induce fat loss as it increases GH levels without affecting appetite [5].
MK-677 Side Effects and Complications
MK-677 has been studied in various clinical settings, and the available research suggests that it is well-tolerated among test subjects.
The longest published MK-677 trial lasted two years and included 65 healthy participants. It involved doses of up to 25mg/daily and reported the following incidence of side effects in the treatment group [19]:
- Increased hunger (67%)
- Joint discomfort (58%)
- Swelling in the lower limbs (44%)
- Muscle soreness (33%)
These side effects were reported as mild and typically diminished within several months of starting MK-677 administration [19].
In another study in nine patients with severe GH deficiency, researchers gave higher doses of 50mg/daily, reporting diarrhea and dry skin as side effects linked to MK-677 [21].
MK-677 has not been authorized for human use and there are no known specific contraindications.
Further, researchers should note that due to their upregulation of GH and IGF-1, GH secretagogues in general may accelerate disease progression in subjects with malignancies.
Sermorelin Side Effects and Complications
Sermorelin has been deemed safe for human use based on the available clinical data and its previous FDA approval for use in children with short stature.
The primary side effects of sermorelin as reported in studies in children have included [7]:
- Facial flushing
- Allergic reactions
- Injections site reactions such as pain, swelling, and induration
Research in adults has also reported similar side effects, with the primary complaints being local effects at the injection site [13, 14].
Only one trial in adults has reported a transient increase in serum lipid levels, which is potentially due to the lipolytic effects of elevated GH levels [12].
Similarly to MK-677, sermorelin could also speed disease progression in subjects with malignancies, due to its effects on GH and IGF-1.
Where to Buy Peptides Online? | 2024 Edition
Researchers interested in exploring the benefits of MK-677 and/or sermorelin may be curious about where to order these compounds online.
Unfortunately, many of the available online vendors offer subpar products that may impede the success of scientific studies.
Our team at Peptideinfo.net has dedicated time and resources to determine the most reputable retailers of research peptides, assessing factors such as quality control, cost, shipping policies, and customer service.
Based on our review of the market, we strongly recommend the following two vendors of research peptides.
Research Peptide for MK-677
Research Peptide is our vendor of choice for MK-677, which is among their top-selling products and is available in a variety of formats and concentrations.
Here are some reasons as to why we trust Research Peptide for MK-677:
- Third-Party Tested MK-677: Research Peptide submits each batch of MK-677 for third-party testing to ensure purity levels of at least 99%. Lab reports are easily available right on the vendor’s MK-677 product pages.
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MK-677 vs. Sermorelin | Verdict
MK-677 and sermorelin differ significantly in their molecular structures, mechanisms of action, and possible outcomes.
MK-677 acts on the ghrelin receptor, while sermorelin is an analog of GHRH and was previously approved as a treatment of growth hormone deficiency in children.
Further, MK-677 has an extended half-life compared to sermorelin and boasts significantly greater oral bioavailability, which allows it to be administered orally once daily.
Regardless of their differences, both compounds are highly effective at increasing GH and IGF-1, which may bring benefits like improved body composition in research subjects.
Researchers looking to investigate the potential of MK-677 and/or sermorelin are well-advised to visit our top recommended vendors.
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