Research Applications
Growth Hormone Deficiency
Phase 2 clinical trials demonstrated MK-677 increases GH and IGF-1 to youthful levels in GH-deficient adults. It produces IGF-1 increases comparable to injectable GH replacement with the advantage of oral dosing.
Sarcopenia and Muscle Wasting
Studies in elderly subjects demonstrated MK-677 (25 mg/day) increased lean body mass, muscle strength, and functional capacity. The GHRS-MK-0677 trial showed significant improvements in body composition in adults over 60 years.
Osteoporosis and Bone Health
Clinical trials demonstrated MK-677 increases bone turnover markers and bone mineral density in postmenopausal women and elderly subjects. Enhanced osteoblast activity through IGF-1 signaling drives increased bone formation.
Hip Fracture Recovery
Studies in elderly hip fracture patients showed MK-677 improved functional recovery and lean body mass, though results on fracture healing itself were mixed.
Sleep Quality
MK-677 significantly increases stage 4 (deep/slow-wave) sleep duration by approximately 50% and REM sleep by 20%. This sleep-promoting effect is attributed to enhanced nocturnal GH pulsatility and is one of the most consistently reported benefits.
Cognitive Function Research
IGF-1 signaling supports neuronal survival and synaptic plasticity. Research in the elderly has explored MK-677's potential to improve cognitive function through sustained IGF-1 elevation, though results have been mixed.
Mechanism of Action
GHS-R1a Agonism (Ghrelin Mimetic)
MK-677 binds to and activates the GHS-R1a (ghrelin/growth hormone secretagogue receptor) as a potent non-peptidic agonist. Despite being structurally unrelated to ghrelin or peptide GH secretagogues, MK-677 activates the same Gq/11-coupled signaling cascade: PLC activation, IP3-mediated calcium release, PKC activation, and GH granule exocytosis from pituitary somatotrophs.
Sustained GH and IGF-1 Elevation
Unlike injectable peptide secretagogues that produce acute GH pulses lasting 2-3 hours, MK-677's oral bioavailability and 4-6 hour plasma half-life produce sustained GH elevation over 24 hours. This results in consistent IGF-1 increases of 40-97% from baseline — maintained with chronic daily dosing without significant tachyphylaxis.
Hypothalamic Actions
MK-677 stimulates GHRH neurons and suppresses somatostatin release at the hypothalamic level, amplifying endogenous GH pulsatility in addition to direct pituitary stimulation. This dual action contributes to the robust and sustained GH response.
Appetite Stimulation
As a ghrelin mimetic, MK-677 activates hypothalamic NPY/AgRP neurons, producing significant appetite stimulation. The orexigenic effect is particularly pronounced during the first weeks of use and partially attenuates over time but remains clinically relevant.
Preserved Pulsatility
Despite sustained GH elevation, MK-677 preserves the pulsatile nature of GH secretion and maintains somatostatin feedback regulation, producing a more physiological GH profile than exogenous GH replacement.
Biological Pathways
PLC/IP3/Calcium/PKC (Somatotroph)
GHS-R1a activation engages Gq/11-PLC-IP3 signaling, producing calcium-dependent GH exocytosis. The sustained receptor activation by MK-677 (due to its oral bioavailability and long half-life) provides extended GH release compared to short-acting peptide agonists.
GH/JAK2/STAT5/IGF-1 Endocrine Axis
Sustained GH release drives continuous hepatic IGF-1 production through JAK2/STAT5 signaling. The resulting 40-97% IGF-1 increase activates the full IGF-1R signaling cascade (PI3K/Akt/mTOR, MAPK/ERK) in target tissues.
AMPK/Hypothalamic Energy Sensing
MK-677 activates hypothalamic AMPK through GHS-R1a signaling, modulating energy balance toward increased food intake and nutrient storage. This contributes to both the appetite stimulation and the anabolic effects on lean body mass.
GH-Mediated Lipolysis
GH activates hormone-sensitive lipase in adipocytes through a JAK2-dependent mechanism, promoting fat mobilization. However, the concurrent insulin resistance induced by sustained GH elevation can partially offset lipolytic benefits.
Dosage Information
Calculation Results
Syringe Fill Level (100u syringe)
Protocols
No protocols featuring this peptide yet.
Browse All ProtocolsStability & Storage
MK-677 is a non-peptidic small molecule, making it significantly more stable than peptide compounds. It is supplied as a white crystalline powder or in capsule/liquid oral formulations. Store at room temperature (15-25°C) in a cool, dry place. Protect from light and moisture.
In powder form, MK-677 is stable for 2+ years when stored properly. Liquid oral solutions (typically in polyethylene glycol or ethanol vehicles) should be stored at room temperature and used within 3-6 months. No reconstitution required — MK-677 is orally bioavailable.
The mesylate salt form (ibutamoren mesylate) provides enhanced aqueous solubility and stability. Unlike peptides, MK-677 is not susceptible to proteolytic degradation and can survive gastric acid exposure, enabling effective oral administration.
Side Effects & Precautions
Increased Appetite and Weight Gain
MK-677 significantly stimulates appetite, particularly during the first 4-8 weeks of use. Caloric intake increases of 300-700 kcal/day have been reported. This can lead to unwanted weight gain if diet is not carefully controlled.
Water Retention and Bloating
Fluid retention is common, particularly during initial use. This includes facial puffiness, ankle edema, and abdominal bloating. GH-mediated sodium retention in the kidneys is the primary mechanism.
Insulin Resistance
MK-677 impairs insulin sensitivity and may increase fasting blood glucose by 5-15 mg/dL. This is a direct effect of sustained GH elevation, which antagonizes insulin signaling in skeletal muscle and liver. Individuals with pre-diabetes or diabetes require careful monitoring.
Lethargy and Drowsiness
Many users report increased sleepiness, particularly during daytime. While enhanced sleep quality at night is generally beneficial, daytime drowsiness can impair function. Dosing before bedtime mitigates this effect.
Numbness and Tingling
Carpal tunnel-like symptoms from GH-mediated fluid retention affecting nerve compression areas. Dose-dependent and reversible.
Joint Pain
Mild to moderate arthralgia occurs in some users, attributed to GH effects on connective tissue. Typically transient.
Prolactin Elevation
MK-677 may modestly increase prolactin levels in some individuals. Usually not clinically significant but should be monitored with chronic use.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Regulatory Status
MK-677 (ibutamoren) is not approved by the FDA or any major regulatory authority for clinical therapeutic use. Merck conducted extensive Phase 2 clinical trials across multiple indications but did not pursue Phase 3 development or seek regulatory approval.
Despite lack of approval, MK-677 is widely available from research chemical companies and supplement retailers. Its non-peptidic, orally available nature has contributed to widespread availability and use outside of clinical settings.
WADA prohibits MK-677 under category S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics) of the prohibited list. It is specifically named as a GH secretagogue and is banned both in-competition and out-of-competition. Several positive doping cases have involved MK-677 detection.
MK-677 is not currently a scheduled controlled substance in the United States, though it is sometimes marketed misleadingly as a "SARM" or "selective androgen receptor modulator" — which is pharmacologically incorrect.
Research Studies
MK-677 (Ibutamoren Mesylate) Stimulates the GH-IGF-1 Axis in Elderly Subjects
Chapman IM, Bach MA, Van Cauter E, et al.
Two-Year Treatment with MK-677 Increases BMD in Elderly Women
Murphy MG, Bach MA, Plotkin D, et al.
MK-677 Increases Sleep Quality and Stage IV Sleep Duration
Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, et al.
Oral Administration of MK-677 in Sustained Recovery of Hip Fracture
Bach MA, Rockwood K, Zetterberg C, et al.
Effects of Ibutamoren Mesylate on Body Composition in Obese Adults
Svensson J, Lönn L, Jansson JO, et al.
Related Peptides
Sermorelin
Sermorelin Acetate, GRF 1-29 +3 more
CJC-1295
CJC-1295 DAC, CJC-1295 with DAC +3 more
GHRP-2
Growth Hormone Releasing Peptide 2, Pralmorelin +3 more
GHRP-6
Growth Hormone Releasing Peptide 6, Growth Hormone Releasing Hexapeptide +3 more
Hexarelin
Examorelin, HEX +2 more
Ipamorelin
IPA, NNC 26-0161 +2 more