MK-677
Ghrelin Receptor Agonist · Oral Growth Hormone Secretagogue
Oral compound that triggers growth hormone release by activating ghrelin receptors, with natural production preserved. Oral bioavailability runs above 60% and half-life is 24 hours, which makes once-daily oral dosing convenient and sets it apart among GH secretagogues.
Overview
Oral compound that triggers growth hormone release by activating ghrelin receptors, with natural production preserved. Oral bioavailability runs above 60% and half-life is 24 hours, which makes once-daily oral dosing convenient and sets it apart among GH secretagogues.
Binding is selective for GHS-R1a receptors of the hypothalamus and pituitary; growth hormone release follows in pulses, and natural circadian patterns are kept intact.
Research indications
What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.
IGF-1 stays elevated 40–72% over extended periods.
In elderly subjects, growth hormone returns to youthful levels, with 24-hour secretion up 97%.
REM rises 20% in younger adults and improves 50% in the elderly.
At 2 weeks, a 15% elevation of basal metabolic rate was documented.
Fat-free mass rises, with accrual weighted toward lean tissue.
Nitrogen retention of +2.69 g/day was demonstrated against -8.97 g/day on placebo, which protects lean mass under caloric restriction.
Bone formation markers rise 39–45% inside 6–8 weeks.
- Class
- Non-peptide ghrelin receptor agonist
- Research status
- Well studied
- Molecular weight
- 624.77 Da
- Half-life
- ~24 h
- Typical dose
- 12.5 mg daily starting; titrated to 25 mg
- Frequency
- Once daily, typically at bedtime on an empty stomach
- Cycle length
- 8–12 weeks for body composition goals
- Storage
- Room temperature in cool, dry place; no refrigeration required
Molecular data
- Type
- Non-peptide ghrelin receptor agonist
- Molecular weight
- 624.77 Da
- Half-life
- 1440 min
Levels in single-dose multiples. A shape, not a pharmacokinetic prediction.
Dosing reference
Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.
| Context | Route | Amount | Frequency |
|---|---|---|---|
| Body composition/anti-aging | Oral (bedtime, empty stomach) | 25mg | 1x daily |
| Sleep quality improvement | Oral (30 minutes before bed) | 25mg | 1x nightly |
| Conservative initiation | Oral (assess tolerance) | 12.5mg | 1x daily |
Interactions
GH pathways complement, giving pulsatile and baseline elevation together.
GH release is stimulated by both, by different mechanisms.
Baseline elevation from MK-677 pairs with the pulsatile spikes of GHRP-2.
Mechanisms do not compete; recovery effects are enhanced.
Localized healing is complemented by systemic growth factors.
Effects are redundant, benefits not proportional.
Insulin sensitivity falls with MK-677, so blood glucose monitoring is required.
A case report on the combination records testosterone suppression of 85.7%, with liver enzymes significantly elevated.
What to expect
Safety
Mechanistic flags — properties of the pathway, not observed adverse events.
- Water retention (30-40%)
- Lethargy (20-30%)
- Fasting glucose up 5–15 mg/dL
- Appetite stimulated in >50% of users
- A note on testosterone suppression: taken alone at up to 20 mg daily, MK-677 is unlikely to suppress testosterone significantly. Past 20 mg daily, suppression grows more likely, as do insulin resistance, water retention and lethargy. In the case report where 85.7% testosterone suppression was documented, LGD-4033 was given alongside — a SARM known for profound suppression, which leaves the SARM as the likely primary driver of that suppression.
- Any concerning cardiovascular symptoms
- Breathlessness, chest pain, or fatigue that is unusual
- Blood glucose >100 mg/dL, or symptoms of diabetes
- Liver enzymes elevated (ALT/AST >2× upper normal)
- Fluid retention that is severe, or swelling that is unexplained
- Diabetes or pre-diabetes
- Active cancer
- Severe cardiovascular disease
- Pregnancy or breastfeeding
- Congestive heart failure or heart disease
Quality checklist
What to confirm before trusting a batch of research material. A verification aid — not an endorsement of any supplier.
- Third-party Certificate of AnalysisIndependent lab · dated · lot-matched.
- HPLC purity ≥ 98%Reverse-phase trace included.
- Mass-spec confirms 624.77 g/molMALDI-TOF or ESI-MS.
- Counterion stated (acetate ≫ TFA)TFA salts can confound bioassays.
- Endotoxin / sterility statementRelevant once reconstituted.
- Lyophilised · cold-chain shippedStored −20 °C, shipped on ice.
- Labelled “research use only”No therapeutic or dosing claims.
Recorded signals for this compound · 8
- ✓Capsules of pharmaceutical grade, professionally labeled
- ✓Expiration dates and batch numbers
- ✓Documentation of third-party testing
- ✓Purity >98% documented on the certificate of analysis
- !A 'for research only' label may mean quality control is absent
- ×Claims of dietary supplement status — the FDA prohibits MK-677 in supplements
- ×No certificates of analysis, leaving purity or source unknown
- ×Prices unusually low, which suggests counterfeit product
FAQ
What makes oral dosing possible for MK-677 when most peptides are injected?
MK-677 is not a peptide at all: it is a small-molecule, non-peptide ghrelin receptor agonist, with oral bioavailability >60% and a half-life of 24 hours. Once-daily oral dosing follows from that, no injections involved, which is uniquely practical among GH secretagogues.
How large is the appetite increase on MK-677?
Appetite stimulation reaches >50% of users at 25 mg. The mechanism is direct ghrelin mimicry — the same one that raises GH. Where the stimulation is problematic, the dose can drop to 12.5 mg, or ipamorelin be used instead for cleaner GH elevation without hunger.
Is water retention common on MK-677?
Yes. Water retention occurs in 30–40% of users, out of the GH stimulation and sodium retention MK-677 produces. Onset falls inside the first 2–4 weeks. Bloating is minimized by sodium management and adequate hydration, and the effect often diminishes over time as the body adapts.
References
- 1Effects 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 menCopinschi, G., et al. · Journal of Clinical Endocrinology & Metabolism · 1996
Randomized, double-blind crossover in 9 healthy young men. 7-day oral MK-677 (5 and 25mg) increased 24-hour GH profiles dose-dependently while preserving circadian patterns.
Human RCTPubMed 8768828 ↗ - 2Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjectsChapman, I.M., et al. · Journal of Clinical Endocrinology & Metabolism · 1996
Randomized, double-blind trial in 32 elderly subjects (64-81 years). 25mg/day MK-677 for up to 4 weeks increased mean 24-hour GH by 97% and restored IGF-I concentrations to young adult levels.
Human RCTPubMed 8954023 ↗ - 3Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in manCopinschi, G., et al. · Neuroendocrinology · 1997
In young adults, 25mg MK-677 increased stage IV sleep duration by 50% and REM sleep by 20%. In older adults, REM sleep increased nearly 50% with decreased REM latency. Sleep deviations dropped from 42% to 8%.
Human RCTPubMed 9349662 ↗ - 4Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditureChapman, I.M., et al. · Journal of Clinical Endocrinology & Metabolism · 1998
24 obese males treated with 25mg/day for 8 weeks showed sustained increases in GH, IGF-I, fat-free mass, and a transient increase in basal metabolic rate at 2 weeks.
Human RCTPubMed 9467542 ↗ - 5MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolismMurphy, M.G., et al. · Journal of Clinical Endocrinology & Metabolism · 1998
Double-blind crossover in 8 healthy volunteers under caloric restriction. 25mg/day MK-677 for 7 days reversed nitrogen wasting (+2.69g/day vs -8.97g/day placebo) and significantly increased IGF-I.
Human RCTPubMed 9467534 ↗ - 6Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adultsMurphy, M.G., et al. · Journal of Bone and Mineral Research · 1999
187 elderly adults (65+) across three placebo-controlled studies. 9 weeks of MK-677 increased serum osteocalcin by 29.4%, bone-specific alkaline phosphatase by 10.4%, and urinary NTX by 22.6%.
Human RCTPubMed 10404019 ↗ - 7Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trialNass, R., et al. · Annals of Internal Medicine · 2008
12-month RCT in 65 healthy adults (60-81 years). MK-677 increased GH and IGF-I to young adult levels, increased fat-free mass while placebo group declined, and was generally well tolerated.
Human RCTPubMed 18981485 ↗
An official communication flagging notable cardiovascular risk with MK-677 and its status as an investigational drug.
In a single-subject case report, combined LGD-4033 and MK-677 use raised total and lean body mass while worsening serum lipids and liver enzymes, with testosterone suppressed 85.7% alongside the SARM.
A male patient in his early 30s developed transaminitis after two months taking MK-677; liver enzymes returned to baseline once the drug was stopped, supporting hepatic monitoring during use.