MK-677, also known as Ibutamoren, is not a SARM but a potent, orally-active, long-acting, selective non-peptide agonist of the ghrelin receptor that acts as a growth hormone secretagogue in vivo . What this means is that like ghrelin, it directly promotes an increase in appetite as well as a sharp increase in human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) secretion, and produces a sustained increase in plasma levels of these hormones without affecting cortisol levels [2,3].
MK-677 Health Research
MK-677 is under investigation as a potential treatment for low levels of HGH and IGF-1 in children or elderly adults with growth hormone deficiency [3,4,5]. MK-677 has demonstrated in human studies that it can increase both muscle mass and bone density, as well as accelerate the growth of connective tissues, making it a promising treatment for frailty in the elderly [6,7].
MK-677 is also being investigated for nootropic effects and the potential to protect the brain from Alzheimer’s disease. MK-677, as a ghrelin mimetic, is an active neuropeptide in the central nervous system and crosses the blood-brain-barrier. In mice, it has been shown to improve sleep quality and protect the brain from β-Amyloid proteins .
MK-677 Investigational Benefit Summary:
1. Mimics Ghrelin to increase and sustain appetite, HGH, and IGF-1 levels
2. Accelerates growth of skeletal muscle and connective tissue, and increases bone mineral density
3. Nonsteroidal and does not interfere with the hypopituitary testicular axis (HPTA)
4. Protects the brain from β-Amyloid proteins, showing potential to decrease risk of Alzheimer’s disease
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2. Copinschi G, Van Onderbergen A, L’Hermite-Balériaux M, Mendel CM, Caufriez A, Leproult R, Bolognese JA, De Smet M, Thorner MO, Van Cauter E (August 1996). “Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men”. The Journal of Clinical Endocrinology and Metabolism. 81 (8): 2776–82. doi:10.1210/jcem.81.8.8768828. PMID 8768828.
3. Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, et al. (December 1996). “Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects”. The Journal of Clinical Endocrinology and Metabolism. 81 (12): 4249–57. doi:10.1210/jcem.81.12.8954023. PMID 8954023
4. Thorner MO, Chapman IM, Gaylinn BD, Pezzoli SS, Hartman ML (1997). “Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging”. Recent Progress in Hormone Research. 52: 215–44, discussion 244-6. PMID 9238854.
5. Chapman IM, Pescovitz OH, Murphy G, Treep T, Cerchio KA, Krupa D, Gertz B, Polvino WJ, Skiles EH, Pezzoli SS, Thorner MO (October 1997). “Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults”. The Journal of Clinical Endocrinology and Metabolism. 82 (10): 3455–63. doi:10.1210/jc.82.10.3455. PMID 9329386.
6. Murphy MG, Bach MA, Plotkin D, Bolognese J, Ng J, Krupa D, Cerchio K, Gertz BJ (July 1999). “Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group”. Journal of Bone and Mineral Research. 14 (7): 1182–8. doi:10.1359/jbmr.19126.96.36.1992. PMID 10404019
7. Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ (March 2001). “Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women”. The Journal of Clinical Endocrinology and Metabolism. 86 (3): 1116–25. doi:10.1210/jcem.86.3.7294. PMID 11238495.
8. Jeong YO, Shin SJ, Park JY, et al. MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease. Int J Mol Sci. 2018;19(6):1800. Published 2018 Jun 18. doi:10.3390/ijms19061800