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Ibutamoren, aka MK-677 is one of many investigational new compounds, that is being tested for several different indications, yet is most commonly known for its off label use a performance enhancing drug. Ibutamoren is an agonist of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren mimics the actions of growth hormone releasing peptide-6 to increase serum levels of serum insulin-like growth factor-I (IGF-I) Ibutamoren, is unique as a dual agonist, yet it is not a traditional peptide. Interested, keep reading.
Ibutamoren, known by its pharmaceutical name MK-677, is a potent, long lasting, orally active, selective, non-peptide agonist, of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren, mimics the action growth hormone and has been shown to increase the secretion of several hormones including insulin-like growth factor-I (IGF-I). Ibutamoren increases plasma levels of hormones, without affecting cortisol levels.
Ibutamoren, is currently being developed by pharmaceutical giant Merck & Co for a variety of indications, including muscle wasting, fibromyalgia, chronic kidney disease, and growth hormone deficiency.
Ibutamoren is one of the most fascinating new pharmaceuticals currently under investigation. Chemically, MK-677 mimics the hunger hormone ghrelin, and functions as a neuropeptide in the central nervous system and crosses the blood-brain barrier.
Growth hormone secretagogues facilitate the release of hormones. Hormone optimization has numerous health benefits including but not limited to improving body composition, increasing muscle mass, promoting fat loss, improving sleep parameters, supporting gut health, stimulating libido, and promoting joint health. Other forms of peptides may help and benefit brain health, and skin health.
Secretagogues are agents or peptides that promote the secretion and release of hormones, neurohormones, chemical neurotransmitters, enzymes, or other molecules synthesized and secreted by cells.
Growth hormone secretagogues (GHS) are synthetic, non-natural peptidyl and non-peptidyl molecules. GHS help facilitate the natural release of hormones such as human growth hormone and IGF-1, insulin-like growth factor, which is a hormone that manages the effects of human growth hormone.
MK-677 is a synthetic nonpeptidyl GHS, that has shown to work directly by mimicking the growth hormone secretion action of ghrelin.
Studies have shown that MK-677 sustains increased pulsatile GH and IGF-1 secretion to levels seen in young adults. The likely mechanism is activation of the ghrelin receptor by MK-677, with feedback by IGF-I preventing excess GH production.
Studies have found, that MK-677 may be a therapeutic agent to help increase muscle mass. A decrease in circulating plasma levels of growth hormone, especially as you age, have been directly correlated with an increase in body fat and loss of lean body mass. Growth hormone is a lipolytic and acts to reduce and redistribute body fat, as well as increase protein synthesis [R].
A study investigating the effects of MK-677 on body composition in older adults, administered 25mg of MK-677 to 65 study participants for 12 months.
The results found, that with MK-677 orally administered, increased fat free mass after 12 months. Fat-free mass accounts for all your body parts that do not contain fat, including organs, bones, tendons, ligaments, muscles, blood, connective tissues, and nerves.
However, it is important to note, that the concomitant increase in intracellular water, which reflects body cell mass (R), is the likely mechanism for the increase in FFM [R].
Growth Hormone reduces abdominal visceral fat (AVF) in GH-deficient adults [R] and abdominally obese, postmenopausal women [R], but not normal elderly subjects [R]. Despite increasing GH levels, MK-677 did not affect AVF.
GH induces several mechanisms for better sleep. The somatotropic axis consisting of growth hormone (GH), insulin-like growth factors (IGF-I and -II), and their associated carrier proteins are intricately involved in normal sleep, as evidenced by the fact that hypothalamic growth hormone-releasing hormone (GHRH) has sleep promoting effects and pituitary growth hormone (GH) release is strongly associated with slow-wave sleep (SWS) [R].
A small study from 1997, published in the journal Nueuroendocrinology researchers found that study participants with high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV sleep and in a more than 20% increase in REM sleep as compared to placebo [R].
Safety and efficacy studies find MK-677 to be well tolerated and safe. However, some of the common reported side effects include
- Joint Pain
- Muscle Pain
- Increased appetite
- Transient edema
Studies show that GH secretion, takes place in a dose dependent manner. Low doses of 5mg, do not show significant increase in IGF. 25mg per day has been shown as an established therapeutic dose for GH secretion [R].
Currently, Ibutamoren MK-677 is under development by Lumos Pharmaceutical and currently in Phase II for the indication of growth hormone deficiency. Studies have found, that ibutamoren is more potent and powerful than other growth hormone secretagogues [R]. It is currently also under investigation for nonalchoholic-fatty liver disease (NASH), sarcopenia, and chronic renal failure.
Ibutamoren, shows significant promise, as a potential therapeutic for growth hormone replacement therapy, and does have significant benefit, on producing endogenous growth hormone. Peptidyl and non-peptidyl development of growth hormone secretagogues, aim to produce a better alternative than endogenous growth hormone, with far fewer side effects.
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