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✔Evidence basedThis article is reviewed by medical professionals for the relevancy and accuracy of the content. Every article is evidence-based and contains references to peer-reviewed studies and academic research.Researchers are continuously exploring innovative alternatives to traditional human growth hormone (hGH) therapy, particularly to address the issues with growth hormone injections.
One promising option that has garnered attention is a growth hormone secretagogue (GHS) known as Ibutamoren, also referred to by its code names MK-677 and L-163,191. Yet, MK-677 has not been approved by regulatory bodies like the US FDA.
Nevertheless, Ibutamoren is under active research as it offers the convenience of being an orally bioavailable stimulant for increasing growth hormone levels, making it a potentially safer and more accessible option.
As research on Ibutamoren progresses, we aim to explore the current evidence, highlighting both the potential benefits and considerations with such compounds as a potential alternative of traditional long-term growth hormone treatment.
What Is MK-677?
Ibutamoren (MK-677) is a GHS, which means it works by mimicking the mechanisms of action of ghrelin, a hormone primarily responsible for stimulating appetite.
Ghrelin and GHS like ibutamoren act on the growth hormone secretagogue receptors (GHS-R) located in the brain, particularly in the pituitary gland. These are not the typical GH-releasing receptors that respond to the growth hormone-releasing hormone (GHRH).
When MK-677 binds to these receptors, it stimulates the natural release of growth hormone. This release increases growth hormone levels significantly, along with insulin-like growth factor 1 (IGF-1), while only causing a brief rise in other pituitary hormones that influence concentrations of cortisol and prolactin.
MK-677 was developed in the 1990s by Merck & Co., a prominent American pharmaceutical company, to create a GHS suitable for oral administration.
The primary purpose of this development was as a treatment for growth hormone deficiency (GHD) effectively without the need for injections.
The only FDA-approved therapy for lack of growth hormone is the administration of growth hormone injections.
Injections is currently the only reliable option for growth hormone replacement therapy because its peptide (made of amino acids) structure is easily broken down in the digestive system, and it cannot pass reliably through the skin or the mucous membranes.
The compound is distinguished as a non-peptide growth hormone secretagogue, which gives it high oral bioavailability, reaching over 60% according to research.
This attribute allows MK-677 to be taken as a form of oral growth hormone therapy rather than via injection, a significant advantage over hGH or peptide-based GHSs.
Lumos Pharma, a biopharmaceutical company specializing in therapies for rare diseases, is currently conducting ongoing studies to investigate MK-677 benefits and health risks in phase-2 clinical trials.
The focus of these trials is on childhood-onset growth hormone deficiency, aiming to assess the effectiveness and safety of MK-677 as an oral treatment for increasing growth hormone levels in children.
Such an oral option would be a popular choice amongst parents, considering the inconvenience of injections for growth hormone-deficient children.
Although research has shown promising results, it is important to note that MK-677 is still categorized as an Investigational New Drug (IND) and has not yet received FDA approval for human use.
Is MK-677 a Steroid?
MK-677 is not approved for human use, and some illegal sellers mislabel it as a SARM (selective androgen receptor modulator) or even a steroid.
However, steroids are synthetic derivatives of testosterone and have a typical steroid structure that directly influences lean muscle growth and other anabolic processes.
In contrast, MK-677 is structurally a spiroindolepiperidine and works by mimicking the action of peptide-based GHSs.
Specifically, evidence-based clinical resources reveal that MK-677 mimics a peptide called growth hormone-releasing peptide-6 (GHRP-6) that activates ghrelin receptors (GHS-R) in the brain and other parts of the body.
MK-677’s activation of ghrelin receptors extends beyond just GH release. Studies show that the compound’s interaction with these receptors throughout the nervous system suggests it may also influence appetite and sleep quality.
MK-677
Increase muscle growth
Improve sleep
Lower cholesterol (LDL) levels
What are the Proven MK-677 Benefits?
Numerous studies indicate that following oral administration of MK-677, growth hormone levels start to rise within 30 to 40 minutes and remain elevated for several hours, potentially reaching a peak of 55.6 ng/ml.
In comparison, the normal standards for the peaks in natural growth hormone level are in the range from 10 to 14 ng/ml. Additionally, MK-677 has a half-life of over 5 hours, contributing to sustained increases in levels of growth hormone release.
In a double-blind randomized study involving 32 healthy elderly participants, ibutamoren resulted in a 55% increase in IGF-1 levels after 2 weeks, rising to 88% by 4 weeks.
MK-677 has garnered interest for its potential benefits for individuals with GHD due to its ability to elevate GH and IGF-1 production over extended periods. These numerous health benefits may include:
- Body Composition: The increase in IGF-1 and growth hormone levels from MK-677 may support muscle growth, supporting a healthy body composition.
- Metabolic Health: Elevated GH levels could enhance metabolic function, possibly reducing excess body fat in obese individuals and improving overall physical health.
- Improvements in Sleep Quality: Since GH is involved in regulating sleep, MK-677 may result in improved sleep quality, particularly non-REM sleep duration in those with GHD.
- Increases in Bone Density: Due to the IGF-1’s role in bone resorption, some studies suggest MK-677 may also increase bone density. It is yet to be studied if it can improve markers of bone turnover in postmenopausal osteoporotic women.
Several trials have noted the specific changes that happen in the body during treatment. Only one study has explored its effects in individuals with health conditions such as growth hormone deficiency (GHD).
In this study, young adults with childhood-onset growth hormone deficiency who took 50mg of MK-677 for 4 days achieved IGF-1 levels similar to those of healthy elderly individuals, suggesting that the compound may be an effective treatment.
Another study involving younger obese males found that two months of oral MK-677 treatment led to an increase in muscle mass of about 3 kg and a temporary rise in basal metabolic rate. However, no significant changes in fat mass were observed during the study or its follow-up.
In a two-year trial involving 65 elderly participants, the study reported a weight gain of 5-7 lbs. over the duration, but there were no changes in fat mass or muscle strength despite increased secretion of growth hormone.
The study also noted a slight reduction in LDL levels and an improvement in bone mineral density, though there were no significant functional improvements in patients with bone fractures.
Short-term trials suggest that the compound may help reverse diet-induced catabolism. Currently, no studies have investigated the effects of MK-677 on catabolic conditions such as protein catabolism, muscle atrophy, or cachexia.
Is MK-677 Safe?
Ongoing phase 2 trials in growth hormone deficiency children are expected to finish by the end of 2024 and to provide comprehensive data on the MK-677 safety.
Long-term studies in healthy older adults have identified the following common ibutamoren side effects:
- Increased appetite
- Mild muscle pain
- Joint pain
- Fluid retention
- Elevated blood sugar levels
- Lower insulin sensitivity
The most frequently reported MK-677 side effect is an increased appetite and hunger pangs, which occur due to the activation of ghrelin receptors. This effect tends to be temporary and usually diminishes with continued use.
Other possible MK-677 side effects include temporary elevations in prolactin, leptin and cortisol levels, as well as increases in thyroid hormones after 1-2 months of treatment. The GHS does not affect the levels of ghrelin or testosterone levels.
Ongoing studies in children with growth hormone deficiency will further investigate MK-677 side effects but most published studies on this GHS have not shown significant adverse effects.
However, one study in elderly adults was prematurely stopped at 24 weeks due to concerns that MK-677 might have contributed to congestive heart failure in people without previous heart failure history.
Below, we explore these and other common concerns associated with ibutamoren side effects.
Can MK-677 Cause Heart Problems?
As mentioned, one clinical trial has noted cardiovascular side effects associated with MK-677 (Ibutamoren) use. In involved subjects over 60 y.o. and the MK-677 groups experienced increase in systolic and diastolic blood pressure.
Specifically, four out of 62 individuals (6.5%) on MK-677 developed congestive heart failure, while only one out of 61 (1.7%) in the placebo group did.
Although increased blood pressure is a risk factor for myocardial hypertrophy and heart enlargement, there is no direct evidence that MK-677 causes heart enlargement. The higher rate of heart failure in the MK-677 group could be linked to their initially elevated blood pressure.
Despite these potential risks, MK-677 does not appear to raise cholesterol levels. Some studies suggest it may reduce LDL ("bad" cholesterol).
Nevertheless, future studies will avoid participants from the elderly population, as well as those with a history of heart failure or other medical conditions like hypertension.
Can MK-677 Cause Brain Damage?
Prolonged use of MK-677 may lead to sustained activation of ghrelin receptors in certain brain regions, raising concerns. However, clinical studies on humans have not shown any negative effects on brain function or emotional health.
On the contrary, some animal research suggests that MK-677 may enhance neurogenesis in the hippocampus, although it did not show protective effects in a rat model of Alzheimer’s disease.
However, there are no studies suggesting any nootropic effects on brain function or cognitive tests. More research on MK-677 and cognitive function is required to fully elucidate its potential.
Does MK-677 Cause Erectile Dysfunction?
MK-677 is a non-selective agonist of the secretagogue receptors, and research shows it can temporarily increase other hormones like prolactin and cortisol levels.
Elevated prolactin can negatively impact libido in both men and women and may lead to infertility and problems with sexual function in men.
However, clinical research, primarily involving older adults, has not reported an increase in erectile dysfunction or infertility compared to a placebo.
Does MK-677 Cause Hair Loss?
No clinical trials have specifically examined whether MK-677 affects hair growth, hair loss, or skin thickness.
However, research shows that MK-677 can significantly increase IGF-1 levels, which may promote hair growth and improve hair strength by stimulating collagen synthesis. The same collagen-boosting effects may also enhance skin thickness.
Does MK-677 Cause Bloating?
MK-677 can cause water retention due to increased hGH levels, potentially leading to limb edema, such as swollen hands and feet. Research indicates that about 2% of participants experience bloating at a 25 mg daily dose, with higher doses likely increasing this incidence.
Additionally, MK-677 may cause bloating by increasing food intake, as it stimulates appetite and food consumption.
The combination of elevated IGF-1, water retention, and increased food intake may also contribute to a condition called “bubble gut” often seen in bodybuilders who use multiple performance-enhancing drugs (PEDs).
This condition, also referred to as Palumboism or "pregnant abs," is characterized by a bulging abdomen despite a lean physique.
What’s the Optimal MK-677 Dosage?
Since MK-677 (Ibutamoren) is not approved for human use, there is no official dosage recommendation.
However, human trials involving MK-677 have typically used daily doses ranging from 10 to 50 mg. Among these, a daily MK-677 dosage of 25 mg is the most common, including in a study that spanned two years.
Bodybuilders who use MK-677 illicitly to achieve an increase in muscle size often favor the 25 mg dose as well. Beginners may start with a lower dose of 10-15 mg per day, gradually increasing their MK-677 dosage as they progress.
This lower range is also sometimes associated with claims of fat loss, although there is no scientific evidence supporting MK-677’s effectiveness in burning fat or aiding in weight loss.
Higher doses of MK-677 may actually lead to an increased risk of ibutamorein side effects such as heightened appetite, elevated blood glucose levels, high blood pressure, and insulin resistance.
The potential toxicity and detrimental health effects from overdosing on Ibutamoren remain unknown.
How Long Does MK-677 Stay in the Body?
Research indicates that MK-677 has an elimination half-life of about 5-6 hours, allowing for once-daily dosing.
Given that it typically takes 4-5 half-lives for a substance to be fully cleared from the body, MK-677 would likely remain in the system for approximately 24-30 hours.
During this time, research reports that MK-677 can be detected in both blood and urine, as it is primarily excreted through urine.
It’s important to note that MK-677 is banned by the World Anti-Doping Agency (WADA) for its potential to increase growth hormone production and can be identified through drug tests.
How Long Does It Take To See Results from MK-677?
Taking MK-677 activates receptors for the hormone ghrelin, leading to an increase in growth hormone production within an hour.
However, research indicates that it takes about two weeks for any measurable changes in the body, such as alterations in body composition, to occur, and up to two months for noticeable results.
In clinical studies, ibutamoren is typically administered in the morning, potentially to avoid interference with the biological rhythms of growth hormone secretion.
However, many bodybuilders prefer taking it in the evening. Taking the peptide at night before bedtime will minimize the increased hunger cravings, as most people typically do not consume any meals at night.
Long-term effects of MK-677, according to research, include:
- Increased lean body mass
- Reduced LDL cholesterol levels
- Increased bone density
What Happens if You Stop Taking MK-677?
Stopping MK-677 use does not result in side effects. Your hGH and IGF-1 levels will simply return to pre-treatment levels, and there is no withdrawal from their hormonal effects.
Many bodybuilders and athletes who use MK-677 illegally tend to cycle on and off to reach their personal goals, despite the lack of scientific evidence supporting this practice.
Ibutamoren does not suppress the endocrine system, so post-cycle therapy (PCT) is unnecessary even after long-term use in clinical trials.