What Is MK-677 (Ibutamoren)?
MK-677, also known as Ibutamoren and Oratrope, is a potent, orally active, selective agonist of the ghrelin receptor. This makes it a growth hormone secretagogue and ghrelin mimetic. It is not a ghrelin analogue, however, as it is not a peptide and therefore shares no structural similarities to ghrelin. Research shows that MK-677 increases the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), but does not affect cortisol levels. This means that MK-677 activates the GH axis and therefore promotes an increase in lean body mass. It is under investigation as a treatment for growth hormone deficiency, muscle and bone wasting, and appetite stimulation. MK-677 is valued for its long half-life and excellent oral bioavailability. Research in humans shows that IGF-1 levels remain elevated for up to 24 hours after a single dose of MK-677.
MK-677 and Somatopause
It has been shown that without intervention, growth hormone secretion and muscle mass decline starting at mid-puberty. This ultimately leads to the frailty and loss of muscle function we see in the elderly. The progressive decline of GH and IGF-1 with age is referred to as somatopause. On average, a male at 70 years of age will produce about 60% of the growth hormone he produced at age 18. This can lead to changes in body composition, loss of bone density, and more. Interestingly, estrogen and progesterone appear to increase GH and IGF-1 levels, thereby reducing the effects of somatopause in women as they age.
MK-677 and Bone Density
Research in young, obese males shows that MK-677 significantly alters bone function by increasing both bone deposition and resorption. Similar results are seen in elderly test subjects. These findings are a classic indication of increased bone remodeling and can be either good or bad depending on the setting. Increased bone remodeling can lead to improved bone strength and resistance to fracture when paired with weight/resistance training, for instance.
MK-677 and Neurological Function
Research in animals has demonstrated that IGF-1 is an important component in the clearance of amyloid beta from the central nervous system. Amyloid beta plaques that result from a build-up of amyloid beta are a hallmark of Alzheimer’s disease (AD) and are indicative of disease severity. It is interesting that AD is a disease of the elderly because IGF-1 levels in the brain have been shown to decrease with age and are even lower in patients suffering from AD. The ability to raise IGF-1 levels could, therefore, provide an effective treatment or preventative for AD.
MK-677 and Sleep
MK-677 has more robust effects on sleep than any of the GHRPs. Research in young adults shows that MK-677 increases stage 4 sleep duration by 50% and increase REM sleep by 20%. In older adults, the results are even more profound, with REM sleep increasing by as much as 50% and REM latency decreasing substantially.
MK-677 and Heart Health
It has long been known that aging leads to impairment of stem cell function. Endothelial progenitor cells (EPCs) are stem cells important in the regeneration of blood vessels. A decline in EPCs has been thought to be a risk factor for the development of atherosclerosis, which can lead to high blood pressure and heart attack among other problems. Research in mice shows that increased GH levels can help to reverse the age-related decline in EPCs and may therefore be useful in preventing heart disease.