MK-677 (Ibutamoren)
Ghrelin Receptor Agonist · Oral Growth Hormone Secretagogue
Overview
Oral compound activating ghrelin receptors to trigger growth hormone release while preserving natural production. Achieves superior oral bioavailability exceeding 60% with a 24-hour half-life, making it unique among GH secretagogues for its convenient once-daily oral dosing.
Selectively binds GHS-R1a receptors in hypothalamus and pituitary, triggering pulsatile growth hormone release while maintaining natural circadian patterns.
Restores youthful growth hormone levels in elderly subjects with 97% increase in 24-hour secretion.
Sustained 40-72% IGF-1 elevation over extended periods.
20% REM increase in younger adults; 50% improvement in elderly.
Demonstrates +2.69g/day nitrogen retention versus -8.97g/day placebo, protecting lean mass during caloric restriction.
Mechanism
Oral compound activating ghrelin receptors to trigger growth hormone release while preserving natural production. Achieves superior oral bioavailability exceeding 60% with a 24-hour half-life, making it unique among GH secretagogues for its convenient once-daily oral dosing.
Selectively binds GHS-R1a receptors in hypothalamus and pituitary, triggering pulsatile growth hormone release while maintaining natural circadian patterns.
Restores youthful growth hormone levels in elderly subjects with 97% increase in 24-hour secretion.
Research areas
- Oral compound activating ghrelin receptors to trigger growth hormone release while preserving natural production. Achieves superior oral bioavailability exceeding 60% with a 24-hour half-life, making it unique among GH secretagogues for its convenient once-daily oral dosing.
- Selectively binds GHS-R1a receptors in hypothalamus and pituitary, triggering pulsatile growth hormone release while maintaining natural circadian patterns.
- Restores youthful growth hormone levels in elderly subjects with 97% increase in 24-hour secretion.
- Sustained 40-72% IGF-1 elevation over extended periods.
- 20% REM increase in younger adults; 50% improvement in elderly.
- Demonstrates +2.69g/day nitrogen retention versus -8.97g/day placebo, protecting lean mass during caloric restriction.
- Increases fat-free mass with preferential lean tissue accrual.
- 15% basal metabolic rate elevation documented at 2 weeks.
- 39-45% increase in bone formation markers within 6-8 weeks.
Research notes
- Appetite stimulation (>50% of users)
- Water retention (30-40%)
- Lethargy (20-30%)
- Fasting glucose elevation (5-15mg/dL)
- Note on testosterone suppression: at doses up to 20 mg daily, MK-677 is unlikely to cause significant testosterone suppression on its own. Above 20 mg daily, the likelihood of suppression and other side effects (insulin resistance, water retention, lethargy) increases. The case report documenting 85.7% testosterone suppression involved co-administration with LGD-4033, a SARM known to be profoundly suppressive, making the SARM the likely primary driver of that suppression.
- Shortness of breath, chest pain, or unusual fatigue
- Blood glucose levels >100mg/dL or diabetes symptoms
- Liver enzyme elevation (ALT/AST >2x upper normal)
- Severe fluid retention or unexplained swelling
- Any concerning cardiovascular symptoms
- Heart disease or congestive heart failure
- Diabetes or pre-diabetes
- Active cancer
- Severe cardiovascular disease
- Pregnancy or breastfeeding
Pharmacokinetics
- Oral compound activating ghrelin receptors to trigger growth hormone release while preserving natural production. Achieves superior oral bioavailability exceeding 60% with a 24-hour half-life, making it unique among GH secretagogues for its convenient once-daily oral dosing.
References
- pubmed.ncbi.nlm.nih.gov/9467534/
- pubmed.ncbi.nlm.nih.gov/9467542/
- pubmed.ncbi.nlm.nih.gov/10404019/
- pubmed.ncbi.nlm.nih.gov/18981485/
- pubmed.ncbi.nlm.nih.gov/9349662/
- pubmed.ncbi.nlm.nih.gov/8768828/
- pubmed.ncbi.nlm.nih.gov/8954023/
FAQs
Why is MK-677 oral when most peptides are injected?
MK-677 is not actually a peptide—it's a small-molecule non-peptide ghrelin receptor agonist with excellent oral bioavailability (>60%) and a 24-hour half-life. This allows convenient once-daily oral dosing without injections, making it uniquely practical among GH secretagogues.
Does MK-677 increase testosterone suppression when combined with SARMs?
At doses up to 20mg daily, MK-677 alone causes minimal testosterone suppression. However, one case report documented 85.7% testosterone suppression when combined with LGD-4033 (a SARM). The SARM was likely the primary driver of suppression, not MK-677.
How much does MK-677 increase appetite?
Appetite stimulation affects >50% of users at 25mg doses. This is direct ghrelin mimicry—the same mechanism that increases GH. If appetite stimulation is problematic, reduce dose to 12.5mg or use ipamorelin instead for cleaner GH elevation without hunger.
Does MK-677 cause water retention?
Yes. 30-40% of users experience water retention from MK-677's GH stimulation and sodium retention effects. This appears within the first 2-4 weeks. Sodium management and adequate hydration help minimize bloating, and effects often diminish over time as the body adapts.