MK-677, also known as Ibutamoren, is a potent, long-acting, orally active, non-peptide growth hormone secretagogue (GHS). Unlike traditional peptides that require injection, MK-677 can be taken orally while still effectively stimulating growth hormone release.
Mechanism of Action
MK-677 works by mimicking the action of ghrelin, the "hunger hormone," binding to ghrelin receptors (GHSR) in the brain. This triggers multiple downstream effects:
- Increases GHRH production from the hypothalamus
- Reduces somatostatin (the hormone that inhibits GH release)
- Amplifies GHRH signaling in the pituitary gland
- Promotes sustained GH pulsatility rather than a single spike
Importantly, MK-677 does not suppress natural GH production or affect cortisol levels, making it distinct from exogenous GH administration.
Research Findings
Growth Hormone & IGF-1 Effects
Clinical studies have demonstrated that MK-677 can increase plasma GH levels by 2- to 10-fold and IGF-1 levels by 1.5- to 3-fold, with effects lasting 6-11 days after a single dose. In a 12-month study of healthy older adults, 25mg/day increased fat-free mass by 1.1 kg compared to placebo.
Body Composition
The ghrelin mimetic MK-677 enhanced pulsatile GH secretion and significantly increased fat-free mass over 12 months with general tolerability. However, improvements in strength and function were not statistically significant despite the increased muscle mass.
Sleep Quality
MK-677 has been shown to increase REM sleep duration and improve overall sleep quality, likely related to its effects on GH secretion patterns which naturally peak during deep sleep.
Bone Density
Research suggests potential benefits for bone mineral density, particularly in elderly populations and postmenopausal women, through increased IGF-1 signaling.
Regulatory Status
MK-677 is NOT approved for human use by the FDA. Products sold as dietary supplements containing ibutamoren are considered illegal and adulterated. In 2017, both the FDA and European Commission granted Orphan Drug Designation for MK-677 in growth hormone deficiency.
MK-677 is prohibited at all times under WADA's Prohibited List as a growth hormone secretagogue.
Safety Profile
Common effects include increased appetite, water retention, mild muscle pain, and elevated fasting glucose. Long-term safety data in humans remains limited.
Research Applications
- Growth hormone deficiency
- Sarcopenia
- Cachexia
- Sleep disorders
- Bone density research