Section 01
What it's used for
Raising GH levels, small trial
In a trial of nine men with severe growth hormone deficiency, oral MK-677 raised IGF-1 by 52% at a 10 mg dose and 79% at 50 mg. Levels did not reach normal range, and the trial did not compare it to injectable GH treatment.
▸Clinical wording
A clinical trial in nine severely GH-deficient adult men found that oral MK-677 raised GH and IGF-1 levels, with IGF-1 rising 52% at the 10 mg dose and 79% at the 50 mg dose from a deficient baseline. The study did not show that these increases reached normal ("youthful") levels, and it did not compare MK-677 to injectable GH replacement.
More lean mass, not more strength
In a year-long trial of healthy older adults, MK-677 (25 mg/day) increased lean body mass by 1.1 kg versus a 0.5 kg loss with placebo. The same trial found this extra mass did not improve muscle strength or physical function.
▸Clinical wording
A randomized trial in healthy older adults found that MK-677 (25 mg/day) increased lean body mass over 12 months (+1.1 kg vs -0.5 kg with placebo). However, the same trial explicitly reported that this increase in fat-free mass did not translate into improvements in muscle strength or functional performance.
Bone markers up, density unclear
In postmenopausal women with osteoporosis, MK-677 alone raised bone-turnover markers vs placebo. Density gains (4.2% vs 2.5% at the hip) appeared only with alendronate added — MK-677 alone was not tested against placebo for bone density.
▸Clinical wording
In a clinical trial in postmenopausal osteoporotic women, MK-677 alone increased bone turnover markers relative to placebo (osteocalcin +22%, urinary NTx +41%). Bone mineral density gains were only reported for MK-677 combined with alendronate versus alendronate alone (4.2% vs 2.5% at the femoral neck); the trial did not report whether MK-677 alone increases bone mineral density versus placebo.
IGF-1 up, recovery mostly unchanged
Two trials in elderly hip-fracture patients found MK-677 raised IGF-1 substantially, but most recovery measures did not improve — only walking speed improved in one trial. Neither trial measured lean mass or actual fracture healing.
▸Clinical wording
Two clinical trials in elderly hip fracture patients found that MK-677 substantially raised IGF-1 levels but produced no significant improvement on most measures of functional recovery — one trial reported no significant differences on functional performance measures, and the other found only gait speed improved significantly, not stair-climbing power. Neither trial reported lean body mass data, and neither measured fracture healing itself.
Deeper sleep, a consistent finding
MK-677 significantly increased deep (slow-wave) sleep by about 50% and REM sleep by 20% in studies, likely by boosting nighttime growth-hormone release patterns. This is one of its most consistently reported effects.
▸Clinical wording
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.
Alzheimer's trial: no benefit shown
In a trial of 563 people with mild-to-moderate Alzheimer's disease, MK-677 raised IGF-1 by 60-73% over 12 months but showed no significant difference from placebo on any cognitive or functional test. The result was uniformly negative.
▸Clinical wording
IGF-1 signaling supports neuronal survival and synaptic plasticity, motivating research into MK-677 for cognitive decline. A randomized clinical trial in 563 patients with mild-to-moderate Alzheimer's disease found that despite raising IGF-1 by 60-73% over 12 months, MK-677 produced no significant difference from placebo on any cognitive or functional endpoint (CIBIC-plus, ADAS-Cog, ADCS-ADL, CDR-sob). The result was uniformly negative, not mixed.
Section 02
Mechanism of Action
Copying the hunger hormone's signal
- It is not a peptide, yet it switches on the same receptor as the hunger hormone ghrelin.
- The receptor releases calcium inside pituitary cells through the usual chain of messengers.
- That calcium pushes stored growth hormone out of the cell.
▸Clinical wording
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.
A round-the-clock rise instead of spikes
- Injected peptide secretagogues give a short burst of growth hormone lasting a few hours.
- This compound works by mouth and stays in blood long enough to lift levels across the day.
- Reported increases in the downstream growth factor run from 40 to 97 percent above starting values.
- Daily use is described as keeping that rise without the response fading.
▸Clinical wording
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.
Acting on the brain as well
- In the brain it stimulates the nerve cells that send the release order for growth hormone.
- It also lowers the braking hormone that normally holds that release back.
- Working on brain and pituitary together is described as producing a larger, longer response.
▸Clinical wording
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.
Hunger goes up, not down
- Because it copies the hunger hormone, it switches on the brain's hunger-driving nerve cells.
- Appetite rises noticeably, most strongly during the first weeks of use.
- The effect weakens partly over time but stays large enough to matter.
▸Clinical wording
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.
The natural rhythm stays intact
- Growth hormone is normally released in waves rather than as a steady stream.
- Even with levels raised overall, that wave pattern and its feedback brake remain.
- The resulting profile is described as closer to natural than injected growth hormone.
▸Clinical wording
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.
Section 03
Biological Pathways
- PLC/IP3/Calcium/PKC (Somatotroph)GHS-R1a activation engages Gq/11-PLC-IP3 signaling for calcium-dependent GH exocytosis; MK-677's oral bioavailability and long half-life sustain this activation, extending GH release versus short-acting agonists.
- GH/JAK2/STAT5/IGF-1 Endocrine AxisSustained GH release drives continuous hepatic IGF-1 production via JAK2/STAT5 signaling; the resulting 40-97% IGF-1 increase activates the IGF-1R cascade (PI3K/Akt/mTOR, MAPK/ERK) in target tissues.
- AMPK/Hypothalamic Energy SensingMK-677 activates hypothalamic AMPK through GHS-R1a signaling, shifting energy balance toward increased food intake and nutrient storage, contributing to appetite stimulation and anabolic effects on lean mass.
- GH-Mediated LipolysisGH activates hormone-sensitive lipase in adipocytes via a JAK2-dependent mechanism, promoting fat mobilization; concurrent insulin resistance from sustained GH elevation may partially offset these benefits.
Section 04
Dosage Information
| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Oral — healthy older adults | Two-year randomised trial, 65 adults aged 60–81 | 25 mg once daily for 24 months — about 280–360 µg/kg for a 70–90 kg adult. Lean mass rose 1.1 kg in a year; placebo lost 0.5 kg | The extra lean mass brought no gain in strength or function. Fasting glucose rose 0.3 mmol/L and insulin sensitivity fell — both held for the full two years. |
| Oral — dose-finding in older adults | 14 and 28 days, 32 healthy adults aged 64–81 | 2, 10 and 25 mg once daily. On 25 mg, IGF-1 went from 141 to 265 µg/L in four weeks and fasting glucose from 5.4 to 6.8 mmol/L | Where the 10–25 mg window comes from — and it is a hormone-response study: weeks long, no health outcome measured, and the glucose rise was there by day 28. |
| Oral — hip-fracture recovery | Phase 2b in 123 elderly patients after hip fracture | 25 mg once daily for 24 weeks in 62 patients against 61 on placebo — about 280–360 µg/kg for a 70–90 kg adult | Stopped early over a heart-failure signal in the treated group; safety was judged unfavourable. IGF-1 rose, walking speed barely moved, stair power not at all. |
| Oral — Alzheimer disease | 12-month randomised trial in 563 patients, mild to moderate | 25 mg once daily for 12 months; blood IGF-1 rose 60% by week 6 and 73% at one year | The largest and longest trial of this compound missed every goal it set: 25 mg held IGF-1 up for a full year, and that on its own changed nothing. |
| Oral — self-administration | Circulating practice outside any trial | 10–25 mg once daily, usually 25 mg at bedtime on an empty stomach, in blocks of weeks to months. It works by mouth and is not injected | Rare case of practice matching the trials — but those ran in people aged 60–81, after hip fracture or with dementia, and at 25 mg measured a glucose rise. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
MK-677 is a non-peptidic small molecule (ibutamoren mesylate), which makes it considerably more stable than peptide compounds and resistant to gastric acid and proteolytic breakdown. Supplied as a white crystalline powder or in capsule/liquid formulations, it is kept at room temperature (15-25°C) in a cool, dry place, protected from light and moisture; the powder form stays stable for 2+ years when stored properly.
After opening
Liquid oral solutions, typically in polyethylene glycol or ethanol vehicles, are kept at room temperature once opened and used within 3-6 months. No reconstitution is needed, as MK-677 is orally bioavailable.
Section 07
Side Effects & Precautions
MK-677's side effects follow from sustained growth hormone elevation: appetite and fluid changes, shifts in insulin sensitivity, sleep changes, and effects on connective tissue and hormones.
Appetite, weight, and fluid retention
- MK-677 significantly stimulates appetite, particularly during the first 4-8 weeks of use, with reported increases in caloric intake of 300-700 kcal/day.
- This can lead to unwanted weight gain if diet is not controlled.
- Fluid retention is common, especially early in use — facial puffiness, ankle swelling, and abdominal bloating — from GH-mediated sodium retention in the kidneys.
Insulin resistance
MK-677 impairs insulin sensitivity and may raise fasting blood glucose by 5-15 mg/dL. This is a direct effect of sustained GH elevation, which works against insulin signaling in skeletal muscle and the liver; the effect is more relevant for people who already have prediabetes or diabetes.
Sleepiness
Many users report increased sleepiness, particularly during the daytime, which can impair function; sleep quality at night is often improved as well.
Joint pain and nerve symptoms
- Numbness and tingling resembling carpal tunnel syndrome can occur from GH-mediated fluid retention around nerve-compression areas; it is dose-dependent and reversible.
- Mild to moderate joint pain (arthralgia) occurs in some users, attributed to GH effects on connective tissue, and is typically transient.
Prolactin elevation
MK-677 may modestly raise prolactin levels in some individuals; this is usually not clinically significant, and prolactin is typically monitored with chronic use.
Section 08
Regulatory Status
Unlike the injectable growth-hormone peptides it is often grouped with, it is an orally active, non-peptidic secretagogue: Merck ran it through Phase 2 trials for several indications but never advanced to Phase 3 or filed for approval.
FDA / United States
Not approved
Merck's Phase 2 programme covered growth-hormone deficiency, hip-fracture recovery and age-related muscle loss, but development stopped there and no application for approval ever followed.
Controlled-substance status
Not scheduled
The DEA does not list ibutamoren as a controlled substance, though sellers sometimes mislabel it a «SARM» — a different, pharmacologically unrelated drug class.
WADA
Prohibited under S2.2.4
It is named explicitly among growth hormone secretagogues, banned at all times, in and out of competition, and several athletes have tested positive for it.
Availability
Sold openly despite no approval
Its oral, non-peptide chemistry lets ibutamoren move through supplement and research-chemical retail channels that injectable, unapproved GH-axis peptides cannot use.
Being unscheduled in the United States is not the same as being approved, and rules differ for athletes, service members and other jurisdictions. Regulatory status changes over time — check current sources before relying on any of this.
Section 09
Research Studies
- [1]Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagoguePatchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, et al. · Proceedings of the National Academy of Sciences · 1995
- [2]A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone ReleaseHoward AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. · Science · 1996
- [3]Peptidomimetic Regulation of Growth Hormone SecretionSmith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, et al. · Endocrine Reviews · 1997
- [4]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 subjectsChapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, et al. · Journal of Clinical Endocrinology & Metabolism · 1996
- [5]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 menCopinschi G, Van Onderbergen A, L'Hermite-Balériaux M, Mendel CM, Caufriez A, Leproult R, et al. · Journal of Clinical Endocrinology & Metabolism · 1996
- [6]Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in manCopinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, et al. · Neuroendocrinology · 1997
- [7]MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolismMurphy MG, Plunkett LM, Gertz BJ, He W, Wittreich J, Polvino WM, et al. · Journal of Clinical Endocrinology & Metabolism · 1998
- [8]Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditureSvensson J, Lönn L, Jansson JO, Murphy G, Wyss D, Krupa D, et al. · Journal of Clinical Endocrinology & Metabolism · 1998
- [9]The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fractureBach MA, Rockwood K, Zetterberg C, Thamsborg G, Hébert R, Devogelaer JP, et al. · Journal of the American Geriatrics Society · 2004
- [10]Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trialNass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE, Clasey JL, et al. · Annals of Internal Medicine · 2008
Section 10
Frequently Asked Questions
In a two-year trial in adults aged 60 to 81, 25 mg daily increased lean body mass by 1.1 kg versus a 0.5 kg loss on placebo. But the same trial explicitly found that extra lean mass did not translate into greater strength or better functional performance — more mass on the scale, not more measured capability.
Yes, consistently across trials. A 28-day dose-finding study found fasting glucose rose from 5.4 to 6.8 mmol/L at 25 mg, and the two-year trial in older adults found fasting glucose up 0.3 mmol/L with reduced insulin sensitivity sustained for the full two years — described as a direct consequence of sustained growth-hormone elevation antagonizing insulin signaling.
IGF-1 rises within weeks — 52 to 79% within about a month in one dose-finding study, 60% by week six in a year-long Alzheimer's trial. Sleep changes (more deep sleep, more REM) are described as an early and consistent effect. Body-composition change was measured at one year in the long-term trial, so how soon lean-mass change appears within that year isn't reported.
This isn't answered in the sourced trials — none of them included a post-discontinuation follow-up or washout period; every outcome was measured while dosing continued. What reverses and how quickly after stopping isn't something the cited research establishes.
There's no data on this in the sourced material one way or the other — every cited trial enrolled adults, mostly aged 60 and older, or people with hip fractures or Alzheimer's disease. None of the safety findings, including blood-sugar changes and a heart-failure signal that stopped one elderly trial early, were measured in adolescents, so the adult findings can't be read as evidence of safety in a younger age group.
Appetite increases substantially, sometimes by 300 to 700 kcal a day, especially in the first month or two. Water retention, daytime drowsiness, carpal-tunnel-like numbness, and joint pain are also reported. In one elderly hip-fracture trial, the treated group showed a heart-failure signal serious enough that the trial was judged unsafe and its safety profile unfavorable.
It has never received FDA approval for any use despite multiple Merck-run phase 2 trials, and it is not a scheduled controlled substance in the US, though it is sometimes mislabeled as a SARM, which is pharmacologically incorrect. WADA prohibits it by name under category S2 as a growth hormone secretagogue, banned both in and out of competition, and it has turned up in positive doping cases.