MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
MK-677 Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
MK-677 (ibutamoren, MK-0677, Nutrobal) is a non-peptide ghrelin-receptor (GHS-R1a) agonist and orally active growth hormone secretagogue. It mimics ghrelin to amplify pulsatile GH release and raise IGF-1 toward young-adult levels for about 24 hours per dose (PMID 8954023, PMID 18678844-era trials). The most-studied dose is 25 mg once daily, often started at 10 mg and titrated. Trials show increased fat-free mass, deeper slow-wave/REM sleep, higher bone-turnover markers, and reversal of diet-induced nitrogen loss, but no gains in strength or physical function and consistent rises in fasting glucose with reduced insulin sensitivity. It is dosed orally (~60-70% bioavailable); the subcutaneous reconstitution scheme here is an educational measurement reference only. MK-677 is not FDA- or EMA-approved, is WADA-prohibited, and is sold for research use only.
Reconstitute: Add 1 mL bacteriostatic water → 20 mg/mL concentration.
Typical dose: 10-25 mg once daily orally
Easy measuring: At 20 mg/mL, 1 unit = 0.01 mL = 0.2 mg (200 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution or commercial liquid refrigerated at 2-8 °C and used within ~4 weeks. Capsules stored at room temperature, protected from light and moisture.
Half-life: Parent compound ~4-6 h (Cmax 1-3 h); pharmacodynamic GH/IGF-1 elevation sustained ~24 h, supporting once-daily dosing.
Route: Oral (10/25 mg capsules or 25 mg/mL solution), ~60-70% bioavailable; modeled here as a subcutaneous reconstitution reference for measurement only.
Status: Not FDA- or EMA-approved; investigational/research use only; prohibited by WADA. Educational content, not medical advice.
About MK-677
MK-677 (ibutamoren) is a small-molecule ghrelin-receptor agonist that acts as an orally active growth hormone secretagogue, mimicking the hormone ghrelin to drive pulsatile GH release and sustained IGF-1 elevation [1][2]. Clinically, and in every published human trial, it is taken by mouth as 10 mg or 25 mg capsules or a 25 mg/mL oral solution once daily; the subcutaneous reconstitution figures below are an educational measurement reference only, not the real-world route.\n\nThis guide models a 20 mg vial reconstituted with 1.0 mL of bacteriostatic water (20 mg/mL) so doses map cleanly onto a U-100 insulin syringe: 10 mg ≈ 50 units, 15 mg ≈ 75 units, and 25 mg ≈ 125 units (which exceeds one syringe and would be split). Most protocols start low at 10 mg/day to gauge appetite and fluid-retention response, then titrate toward the 25 mg/day clinical-trial standard [2][3].\n\nFrequency: Once daily, at a consistent time (many prefer the evening because of pronounced effects on slow-wave sleep). MK-677 is not FDA- or EMA-approved and is presented here for educational purposes only.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner wall of the 20 mg MK-677 vial; do not aim the stream directly at the powder, and avoid vigorous shaking.
Gently swirl or roll the vial until the solution is completely clear; the result is a 20 mg/mL concentration (200 mcg per insulin-syringe unit).
Store refrigerated at 2-8 °C; draw the prescribed number of units per dose (10 mg ≈ 50 units, 15 mg ≈ 75 units, 25 mg ≈ 125 units, which is split across two injections).
Educational note: MK-677 is clinically taken ORALLY once daily — these subcutaneous reconstitution figures are a measurement reference only; for subcutaneous educational modeling, inject slowly without aspirating and wait a few seconds before withdrawing the needle.
Interactive MK-677 Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 1mL water yields 20.00 mg/mL. To evaluate a 250mcg dose, pull to 1.3 units (1 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Weeks 1-2 — titration start | 10000 mcg (10 mg) | 50 units (0.50 mL) |
| Weeks 3-4 — common maintenance | 15000 mcg (15 mg) | 75 units (0.75 mL) |
| Week 5+ — clinical-trial standard | 25000 mcg (25 mg) | 125 units (1.25 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (MK-677, 20 mg each):
- check8 weeks at 10 mg/day ≈ 28 vials (560 mg total)
- check12 weeks at 15 mg/day ≈ 63 vials (1,260 mg total)
- check16 weeks at 25 mg/day ≈ 140 vials (2,800 mg total) — the high count illustrates why MK-677 is dosed orally in practice
Insulin Syringes (U-100):
- checkOnce-daily dosing: 7 syringes per week
- check8 weeks ≈ 56 syringes; 12 weeks ≈ 84 syringes; 16 weeks ≈ 112 syringes
- checkDoses of 25 mg exceed one 1 mL syringe (≈125 units) and need a split (2 × ~63 units), roughly doubling syringe use
Bacteriostatic Water (30 mL bottles): Use 1 mL per 20 mg vial for reconstitution.
- check8 weeks (10 mg/day) ≈ 28 mL ≈ 1 bottle
- check12 weeks (15 mg/day) ≈ 63 mL ≈ 2-3 bottles
- check16 weeks (25 mg/day) ≈ 140 mL ≈ 5 bottles
Alcohol Swabs:
- check1-2 swabs per dose (vial top + injection site)
- check8 weeks ≈ 60-120 swabs; 12 weeks ≈ 90-170 swabs
- check16 weeks ≈ 120-230 swabs; keep extras for re-swabbing multi-use vials
Mechanism of Action (MOA)
MK-677 is a spiropiperidine small molecule (L-163,191) engineered by Merck chemists to mimic the growth-hormone-releasing peptide GHRP-6 while remaining orally active and metabolically stable [1]. It is not a peptide; it is a non-peptidic agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the same receptor activated by the endogenous hormone ghrelin. By binding GHS-R1a on pituitary somatotrophs and on hypothalamic neurons, MK-677 amplifies the natural pulsatile release of growth hormone: it increases GH pulse amplitude, potentiates the action of growth-hormone-releasing hormone (GHRH), and blunts inhibitory somatostatin tone [1][2]. The downstream consequence is a rise in hepatic insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3. In healthy elderly subjects, 25 mg/day increased 24-hour mean GH by roughly 97% and restored IGF-1 into the young-adult range within two to four weeks [2].\n\nBecause it preserves the pulsatile, feedback-regulated pattern of GH secretion rather than flooding the system with exogenous GH, MK-677 raises IGF-1 without fully overriding negative feedback, although it does not prevent the metabolic consequences of sustained GH/IGF-1 elevation, notably reduced insulin sensitivity and higher fasting glucose [2][3].\n\nPharmacokinetics: MK-677 is orally bioavailable at roughly 60-70%, reaches peak plasma concentration (Cmax) in about 1-3 hours, and the parent molecule has a relatively short elimination half-life of approximately 4-6 hours. Its pharmacodynamic footprint is far longer: a single daily dose sustains elevated GH and IGF-1 for about 24 hours, which is why once-daily dosing is sufficient [2][3]. Metabolism is primarily hepatic via CYP3A4 oxidation, so strong CYP3A4 inhibitors or inducers can shift exposure.\n\nBecause it also activates ghrelin receptors outside the GH axis, MK-677 produces ghrelin-like effects: marked stimulation of appetite, modest sodium and fluid retention (transient peripheral edema and arthralgia, especially early), and changes in sleep architecture. Controlled polysomnography showed roughly 50% increases in stage IV slow-wave sleep in young subjects and increased REM duration in older subjects [6]. Documented anabolic effects include increased fat-free mass and body weight, reversal of diet-induced nitrogen wasting, and elevated markers of bone formation and resorption [3][4][5]. Importantly, despite these biomarker changes, controlled trials did not demonstrate improvements in muscle strength, physical function, or — in the case of Alzheimer's disease — disease progression, even though IGF-1 target engagement was confirmed [3][7].\n\nThe real-world route is oral; the subcutaneous reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method. MK-677 is not approved by any major regulator and is restricted to research use [8].
Clinical Trial Efficacy Highlights
- starPatchett, Nargund and colleagues (1995) characterized L-163,191 (MK-0677) as a potent, orally active non-peptide GH secretagogue that releases GH from rat pituitary cells with an EC50 of roughly 1.3 nM, acting through the same mechanism as GHRP-6 but distinct from GHRH, and elevating GH in dogs at oral doses as low as 0.125 mg/kg without significant effects on cortisol, prolactin, thyroxine or LH [1].
- starChapman and colleagues (1996, JCEM) gave healthy elderly subjects daily oral MK-677 for up to four weeks; 25 mg/day enhanced pulsatile GH release, raised 24-hour mean GH by approximately 97%, and restored serum IGF-1 into the normal young-adult range, while also significantly increasing fasting glucose and IGF-binding protein 3 [2].
- starNass and colleagues (2008, Annals of Internal Medicine) ran a 2-year double-blind randomized trial in 65 healthy adults aged 60-81 using 25 mg/day; MK-677 increased fat-free mass by about 1.1-1.6 kg relative to placebo and sustained GH/IGF-1 in the young-adult range, but produced no gains in strength or function and increased fasting blood glucose with reduced insulin sensitivity [3].
- starMurphy and colleagues (1998, JCEM) showed that 25 mg/day for 7 days reversed diet-induced protein catabolism in calorically restricted healthy young men, shifting nitrogen balance from net wasting toward positive balance and significantly increasing IGF-1, supporting an anabolic, nitrogen-sparing effect during caloric restriction [4].
- starThe MK-677 Study Group (Murphy et al., 1999, Journal of Bone and Mineral Research) pooled 187 elderly adults across three placebo-controlled studies and found that once-daily MK-677 raised IGF-1 and increased biochemical markers of both bone formation and bone resorption, indicating stimulation of overall bone turnover [5].
- starCopinschi and colleagues (1997, Neuroendocrinology) used polysomnography in a 7-day randomized trial and reported that MK-677 increased stage IV slow-wave sleep by roughly 50% in young subjects and increased REM sleep duration in older subjects, while reducing the frequency of abnormal sleep episodes in both groups [6].
- starSevigny and colleagues (2008, Neurology) randomized 563 patients with mild-to-moderate Alzheimer's disease to 25 mg/day MK-677 or placebo for 12 months; despite confirmed target engagement (a clear rise in serum IGF-1), MK-677 did not slow disease progression, illustrating that biomarker elevation does not guarantee clinical benefit [7].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningMarkedly increased appetite is the most consistent effect, driven by ghrelin-receptor activation; this can promote weight gain and complicate fat-loss goals [3].
- warningFluid and sodium retention can cause transient peripheral edema, joint and muscle aches (arthralgia/myalgia), and a sensation of fullness or puffiness, typically most pronounced in the first weeks of use [2][3].
- warningReduced insulin sensitivity and rising fasting glucose were observed across trials at 25 mg/day, a clinically important metabolic concern; people with prediabetes, diabetes, or metabolic syndrome are at particular risk [2][3].
- warningLethargy, daytime drowsiness, headache, and altered sleep can occur, partly reflecting the compound's pronounced effects on slow-wave and REM sleep [6].
- warningSustained elevation of GH and IGF-1 raises theoretical long-term concerns (e.g., effects on glucose metabolism, soft-tissue growth, and potential tumor promotion); the FDA has also warned of a potential for congestive heart failure in susceptible individuals, with at least one trial program raising cardiac safety questions.
- warningDespite biomarker improvements, controlled trials showed no improvement in muscle strength or physical function and no benefit in Alzheimer's disease progression, so claimed performance/anti-aging benefits are not supported by clinical endpoints [3][7].
- warningMK-677 is metabolized largely via hepatic CYP3A4; strong CYP3A4 inhibitors or inducers may alter exposure, and combining with other GH secretagogues or insulin-affecting agents can compound metabolic risk.
- warningRegulatory/research status: MK-677 is NOT approved by the FDA or EMA for any use, cannot legally be sold as a dietary supplement, is prohibited by WADA, and is sold only for research; long-term human safety is not established [8].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical MK-677 dosage?expand_more
In published human trials the standard MK-677 dosage is 25 mg once daily by mouth (Chapman 1996, Nass 2008, Sevigny 2008). Many people start lower, around 10 mg/day, to gauge appetite stimulation and fluid retention, then titrate up over a few weeks. The practical range is about 10-25 mg once daily. Because it is dosed in milligrams rather than micrograms, MK-677 is taken orally as capsules or a 25 mg/mL solution; the subcutaneous figures on this page are an educational measurement reference only.
Is MK-677 FDA approved?expand_more
No. MK-677 (ibutamoren) is not approved by the FDA or EMA for any indication. It was investigated by Merck and others but never reached approval. The FDA classifies it as an unapproved drug that cannot legally be sold as a dietary supplement, it is on the WADA Prohibited List, and the FDA has warned of safety risks including potential congestive heart failure. It is sold only for research use, and this page is educational, not medical advice.
What is the half-life of MK-677?expand_more
The parent molecule has a relatively short elimination half-life of about 4-6 hours, with peak plasma concentration (Cmax) reached roughly 1-3 hours after an oral dose. However, the pharmacodynamic effect is much longer: a single daily dose keeps growth hormone and IGF-1 elevated for about 24 hours, which is why once-daily dosing is effective. Oral bioavailability is approximately 60-70%, and the compound is cleared mainly by hepatic CYP3A4 metabolism.
How is MK-677 reconstituted and administered?expand_more
Clinically MK-677 is swallowed (capsule or oral solution), so no reconstitution is needed in real-world use. For the educational subcutaneous model on this site, a 20 mg vial is mixed with 1.0 mL of bacteriostatic water to give 20 mg/mL; draw the water slowly down the vial wall, swirl gently until clear, and refrigerate. At that concentration 10 mg ≈ 50 units and 15 mg ≈ 75 units on a U-100 insulin syringe, while a 25 mg dose (≈125 units) exceeds one syringe and would be split.
Can MK-677 be stacked with other compounds?expand_more
In research and anecdotal practice MK-677 is sometimes combined with injectable GH secretagogues (e.g., ipamorelin or CJC-1295) or SARMs, but this is not supported by controlled safety data and raises specific risks. Stacking compounds that elevate GH/IGF-1 or affect glucose metabolism can worsen insulin resistance, fluid retention, and fasting glucose, all of which MK-677 already causes. Because it is metabolized by CYP3A4, drugs that inhibit or induce that enzyme can change exposure. There is no validated stacking protocol; treat any combination as experimental.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing MK-677, plus the universal dosing calculator.
Academic References & Study Citations
Patchett AA, Nargund RP, Tata JR, et al. Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc Natl Acad Sci U S A. 1995;92(15):7001-7005. View Scientific Paper →
Chapman IM, Bach MA, Van Cauter E, et al. Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab. 1996;81(12):4249-4257. View Scientific Paper →
Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008;149(9):601-611. View Scientific Paper →
Murphy MG, Plunkett LM, Gertz BJ, et al. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 1998;83(2):320-325. View Scientific Paper →
Murphy MG, Weiss S, McClung M, et al. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group. J Bone Miner Res. 1999;14(7):1182-1191. View Scientific Paper →
Copinschi G, Leproult R, Van Onderbergen A, et al. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology. 1997;66(4):278-286. View Scientific Paper →
Sevigny JJ, Ryan JM, van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. 2008;71(21):1702-1708. View Scientific Paper →
Operation Supplement Safety (OPSS), U.S. Department of Defense. Performance Enhancing Substance: MK-677 (Ibutamoren) — unapproved drug, not legal in dietary supplements, WADA-prohibited. View Scientific Paper →