MK-677

MK-677, also known as Ibutamoren or Nutrobal, is a non-peptide ghrelin mimetic that stimulates growth hormone secretion through oral administration. Unlike injectable peptide secretagogues, MK-677 can be taken as a capsule or liquid, making it uniquely convenient. Originally developed by Merck as a potential treatment for growth hormone deficiency, muscle wasting, and osteoporosis, MK-677 has been extensively studied in clinical trials. While it has not achieved regulatory approval, research has demonstrated significant increases in GH and IGF-1 levels with chronic oral administration. The compound's long half-life allows for once-daily dosing, producing sustained elevation of growth hormone levels over 24 hours. This differs from injectable secretagogues that produce acute GH pulses.

MK-677 works through ghrelin receptor activation: **Ghrelin Mimetic**: MK-677 binds to the ghrelin receptor (GHS-R1a) in the pituitary and hypothalamus, mimicking the action of endogenous ghrelin on growth hormone release. **Sustained Action**: Unlike ghrelin which has a very short half-life, MK-677's 24-hour half-life provides continuous receptor stimulation and sustained GH elevation. **IGF-1 Increase**: Through chronic GH elevation, MK-677 significantly increases circulating IGF-1 levels, which mediates many anabolic effects. **GH Pulsatility**: Despite continuous receptor occupation, some degree of GH pulsatility is maintained, though blunted compared to intermittent peptide administration. **Appetite Stimulation**: As a ghrelin mimetic, MK-677 activates appetite centers, often leading to increased hunger—particularly in the initial weeks of use.

MK-677 has extensive clinical research: **IGF-1 Elevation**: Studies show MK-677 increases IGF-1 levels by 40-60% in most populations, with effects sustained during chronic administration. **Body Composition**: Clinical trials in elderly subjects demonstrated increased lean body mass and some reduction in fat mass over 12 months of treatment. **Bone Health**: Research in postmenopausal women showed improvements in bone turnover markers and bone mineral density with 18 months of treatment. **Sleep Quality**: Studies have documented increased REM sleep and overall sleep quality, likely mediated through central ghrelin receptor effects. **Muscle Preservation**: In various catabolic conditions, MK-677 has shown ability to preserve lean tissue and prevent muscle wasting. **GH Profile**: Studies confirm significant and sustained increases in GH levels, with peak levels approximately 2-fold higher than baseline.

MK-677 dosing is well-established from clinical trials: **Standard Dose**: 25mg once daily has been used in most clinical studies. **Dose Range**: Research has employed doses from 5-25mg daily, with dose-dependent increases in GH and IGF-1. **Timing**: Evening administration is often preferred due to enhanced sleep effects, though it can be taken any time. **Duration**: Clinical trials have lasted up to 2 years without loss of efficacy or significant safety concerns. **No Cycling Required**: Unlike injectable secretagogues, MK-677 has shown sustained efficacy without apparent receptor desensitization in long-term studies.

MK-677's side effect profile reflects its ghrelin mimetic activity: **Common**: - Increased appetite (especially weeks 1-4) - Water retention and bloating - Mild lethargy (often improves with time) - Numbness or tingling in hands **Less Common**: - Elevated fasting blood glucose - Insulin resistance (with long-term use) - Joint pain or stiffness - Vivid dreams **Metabolic Considerations**: Long-term MK-677 use may impair insulin sensitivity. Monitoring of fasting glucose is advisable. **Contraindications**: Diabetes or pre-diabetes, active cancer, congestive heart failure (due to water retention).