MK-677 (Ibutamoren / Ibutamoren Mesylate)
PeptideThe divergence of −20 points is explained by the community placing high value on subjective sleep and body composition effects [c1, c2], whereas the medical assessment is substantially limited by absent long-term safety data, insulin resistance risk, and lack of regulatory approval [s7, s8, s11, s12].
Unlock full information
Dosages, side effects, studies and more — free after registration.
Register for freeRating Scales
TL;DR
MK-677 consistently raises GH and IGF-1 levels and increases lean body mass across multiple controlled trials — that is its strongest and most reproducible finding. However, insulin resistance is not a rare side effect but a mechanistically expected, documented risk that warrants serious consideration with long-term use. In Germany the substance is unapproved, its sale for human consumption is illegal, and it is explicitly banned in competitive sport as a growth hormone secretagogue. Product quality from unregulated sources is a genuine concern: contamination and mislabelled dosing have been documented.
Description
Oral ghrelin receptor agonist that stimulates GH and IGF-1 secretion. Not approved for human use; experimental application in bodybuilding and biohacking community [s1, s2].
MK-677 (Ibutamoren) is a synthetic, non-peptidic, selective agonist at the ghrelin receptor (GHS-R1a). The compound was originally developed by Merck & Co. and investigated in clinical trials for applicability in growth hormone deficiency, sarcopenia, and osteoporosis [s1, s3, s5]. Unlike exogenous growth hormone (HGH), MK-677 stimulates endogenous, pulsatile GH secretion from the pituitary gland, thereby secondarily elevating circulating IGF-1 levels [s1, s2]. Clinical studies demonstrated a significant increase in lean body mass in healthy older adults after 12 months [s3], as well as improvements in REM and deep sleep phases in young subjects [s6]. A systematic review including 5 studies confirmed positive effects on GH/IGF-1 levels and muscle mass in older individuals [s5]. Clinically relevant safety concerns include insulin resistance, water retention, increased appetite, and a theoretical risk of promoting pre-existing tumors through elevated IGF-1 levels [s7, s8]. The FDA has explicitly warned against uncontrolled use, as products are frequently contaminated or mislabeled [s11]. MK-677 is actively used in the biohacking and bodybuilding community, despite not being approved as a medicinal product for human use in any country [s11, s12].
Legal Status (DE)
In Germany, MK-677 (Ibutamoren) is neither approved as a medicinal product nor marketable as a dietary supplement. Under German law, it is classified as an unapproved substance with medicinal product character (AMG). Sale for human consumption is unlawful. Ibutamoren is listed in the annex of the German Anti-Doping Act (NADAG) as a growth hormone secretagogue, explicitly prohibiting its use in competitive sports under doping control [s12, s13]. Possession of small quantities for personal use may fall into a legal grey area under criminal law, but is not permitted under regulatory frameworks [s13].
Mechanism of Action
MK-677 binds selectively and with high affinity to the ghrelin receptor (GHS-R1a), which is primarily expressed in the hypothalamus and anterior pituitary [s1, s2]. As a full agonist at GHS-R1a, MK-677 mimics the action of the endogenous hunger hormone ghrelin, but without its peptide structure and thus with significantly higher oral bioavailability [s1, s2]. At the hypothalamic level, GHS-R1a activation stimulates the release of Growth Hormone Releasing Hormone (GHRH) while simultaneously suppressing somatostatin, the physiological GH inhibitor [s1]. In the pituitary, MK-677 acts directly on somatotropic cells, thereby amplifying pulsatile GH secretion [s3]. The elevated circulating GH subsequently stimulates hepatic synthesis and secretion of IGF-1 (Insulin-like Growth Factor 1) [s1, s5]. IGF-1 mediates anabolic effects in muscle and bone tissue: it promotes protein synthesis, inhibits proteolysis, and stimulates osteoblast activity [s5]. Oral bioavailability is established; the half-life is approximately 24 hours, enabling once-daily dosing [s4]. Hepatic metabolism occurs primarily via CYP3A4 [s4]. Since GHS-R1a is also expressed in the gastrointestinal tract and limbic system, this accounts for the pronounced appetite-stimulating effect as well as potential influences on mood and cognition [s1, s9]. GH secretion induced by MK-677 does not measurably increase endogenous cortisol production; however, it negatively affects insulin sensitivity through GH-induced insulin resistance [s7, s8].
Dosing
Muskelaufbau / Körperzusammensetzung (ältere Erwachsene, klinische Studiendosis)
- Dose
- 25 mg daily
- Frequency
- 1× täglich
- Route
- oral
- Duration
- 12 Monate (klinische Studie)
- Timing
- Evening, approx. 30 minutes before bedtime (to minimize hunger effect)
- With food
- optional
Schlafqualität (klinische Studiendosis, junge Erwachsene)
- Dose
- 25 mg daily
- Frequency
- 1× täglich abends
- Route
- oral
- Duration
- 2 Wochen (klinische Studie)
- Timing
- Evening before bedtime
- With food
- optional
GH/IGF-1-Stimulation (niedrige Dosis, explorativ)
- Dose
- 10 mg daily
- Frequency
- 1× täglich
- Route
- oral
- Duration
- variabel
- Timing
- Evening
- With food
- optional
Doses up to 50 mg/day have been investigated in clinical studies [s3, s10]. A dose of 25 mg/day represents the most commonly used clinical study dose [s3, s6]. Doses exceeding 25 mg are not supported by controlled human studies demonstrating improved efficacy and are associated with increased risk of adverse effects. MK-677 is not approved for human use; any application occurs outside the regulatory framework [s11, s12].
Evening administration is recommended, as GH is physiologically secreted in a pulsatile manner during sleep and the appetite-stimulating effect is more manageable at that time [s6, c1]. The half-life of approximately 24 hours permits once-daily dosing [s4]. No regulatory-approved dosing regimen exists, as no approval has been granted [s12].
Calculate reconstitution, plan dosing, look up injection technique
Side Effects
| Side Effect | Frequency | Severity |
|---|---|---|
| Gesteigerter Appetit / Hungergefühl Direct consequence of GHS-R1a activation in the gastrointestinal tract and hypothalamus, generating ghrelin-like hunger signals. Reported nearly universally [s1, s2, c1, c2]. | häufig | leicht |
| Wasserretention / periphere Ödeme GH-induced renal sodium retention leads to fluid accumulation, particularly during the adaptation phase. Consistently reported in clinical studies and community [s3, s7, c1]. | häufig | leicht |
| Insulinresistenz / Erhöhung des Nüchternblutzuckers GH increases hepatic and peripheral insulin resistance. In clinical studies, fasting blood glucose rose by an average of ~5 mg/dL. Long-term use carries an increased risk of type 2 diabetes [s7, s8, s11]. | häufig | moderat |
| Gelenk- und Muskelschmerzen (Arthralgie, Myalgie) Possibly mediated by elevated GH/IGF-1 levels and fluid accumulation in joint capsules. Described by users and in studies [s7, s11]. | gelegentlich | leicht |
| Tagesmüdigkeit / Lethargie Reported particularly during the adaptation phase; possible consequence of deepened nocturnal sleep (slow-wave sleep) or GH secretion [c1, c2]. | gelegentlich | leicht |
| Herzinsuffizienz-Exazerbation (bei Risikopatienten) In a clinical study with elderly patients (hip fracture), an increased rate of heart failure was observed in the MK-677 arm. Causality unclear, but clinically relevant for at-risk populations [s3, s8]. | selten | schwer |
| Potenzielle Förderung präexistenter IGF-1-sensitiver Tumoren Chronically elevated IGF-1 levels are associated with increased tumor growth risk (particularly prostate, colon, and breast carcinoma). Direct evidence for carcinogenesis by MK-677 in humans is lacking; however, the theoretical risk cannot be excluded [s8, s9]. | theoretisch | schwer |
| Taubheitsgefühl / Parästhesien (Karpaltunnelsyndrom-ähnlich) GH-associated carpal tunnel syndrome due to tissue swelling; described by users and in studies [s7, s11]. | gelegentlich | leicht |
Contraindications
Chronically elevated IGF-1 levels can promote the growth of existing tumors. In patients with known carcinoma or predisposition, this is considered an absolute contraindication [s8, s9].
MK-677 impairs insulin sensitivity and increases fasting blood glucose. In pre-existing glucose metabolism disorders, there is an increased risk of metabolic decompensation [s7, s8].
In a clinical trial with elderly patients (hip fracture), heart failure events occurred more frequently in the MK-677 arm [s3].
No safety data available for pregnancy or lactation. Growth factor activation could affect embryonic/fetal development [s12].
GH/IGF-1 elevation with open epiphyseal plates can lead to uncontrolled bone growth and acromegaly-like changes [s12].
Further elevation of already increased GH/IGF-1 levels is contraindicated [s1, s12].
Interactions
Synergistic
Combined stimulation of the GH axis via different receptors can produce synergistic GH secretion; increased risk of side effects (insulin resistance, edema) [s1].
Frequently combined in the community for muscle building; additive anabolic effects possible, but cumulative side effect and legal risks [c3].
MK-677 and GHRP-2 both act via the GHS-R1a receptor; combination may lead to additive or supra-additive GH secretion, but carries the risk of receptor desensitization with long-term use.
MK-677 and GHRP-6 share the same receptor pathway; combinations may produce synergistic GH secretion, but long-term use carries the risk of receptor overstimulation or desensitization.
MK-677 and ipamorelin share GHS-R1a as their primary receptor; the combination may produce enhanced GH release, particularly when a GHRH analogue is additionally employed.
Hexarelin and MK-677 both stimulate GH release via the ghrelin receptor; combined use can augment GH secretion but also increases the risk of side effects such as insulin resistance.
Combining a GHRH analogue such as CJC-1295 with MK-677 simultaneously activates two distinct receptor systems, producing synergistic GH secretion of up to 3–5-fold compared to single administration.
BPC-157 and MK-677 act via complementary mechanisms; BPC-157 promotes local tissue regeneration and healing, while MK-677 supports systemic anabolic and regenerative processes via GH/IGF-1.
Berberine may counteract MK-677-induced insulin resistance by improving insulin sensitivity via AMPK activation; this combination is recommended in the community to reduce metabolic side effects.
CJC-1295 without DAC activates the GHRH receptor, MK-677 the GHS-R1a; dual-receptor stimulation produces synergistic GH secretion of 2–3-fold compared to single administration. Both mechanisms of action complement each other.
Sermorelin acts as a GHRH analogue via the GHRH receptor, MK-677 via GHS-R1a; combining both receptor pathways may synergistically enhance GH secretion. This combination is described for broad anabolic and regenerative support.
Tesamorelin is a GHRH analogue and activates a different receptor pathway than MK-677; the combination can produce synergistic GH release via dual receptor stimulation. Particularly relevant for body composition and visceral fat reduction.
TB-500 promotes tissue regeneration and angiogenesis at the cellular level, while MK-677 systemically elevates GH/IGF-1 and supports anabolic processes. The combination is used in the community for accelerated muscle and tissue building.
Caution
MK-677 increases insulin resistance and fasting blood glucose; dose adjustment of antidiabetic agents is necessary, increased hypoglycemia risk possible with concurrent insulin administration [s7, s8].
MK-677 is metabolized via CYP3A4; inhibitors can increase plasma levels and potentiate the risk of adverse effects [s4].
Both substances negatively affect insulin sensitivity; additive diabetogenic effect possible [s7].
GH/IGF-1 alterations may affect hepatic metabolism; interaction potential is theoretical [s4].
MK-677 raises blood glucose and reduces insulin sensitivity; concurrent use of metformin may be beneficial to attenuate this effect, but requires medical supervision and possible dose adjustment.
Both substances influence the endocrine axis at different levels; uncontrolled combination may promote hormonal imbalances and should only be undertaken under medical supervision.
MK-677 does not suppress testosterone production and does not require PCT with enclomiphene; concurrent use is generally not indicated and may unnecessarily burden the endocrine axis. Enclomiphene is not required following MK-677 use.
MK-677 affects the endocrine GH/IGF-1 axis; ashwagandha modulates cortisol and testosterone via the HPA axis. As MK-677 may initially slightly elevate cortisol levels according to some reports, ashwagandha could theoretically attenuate this effect; however, the evidence for a direct interaction is limited.
Studies
Tier A — High Evidence
Outcome: No significant difference in CIBIC-plus score or ADAS-Cog after 12 months; target engagement confirmed (IGF-1 increase), but no clinical benefit for AD progression.
Community Evidence
Top reported benefits
- Markedly improved sleep quality and deeper sleep
- Enhanced muscle growth and post-workout recovery
- Increased appetite (considered beneficial during bulking phases)
- Improved skin appearance and nail growth
- Increased energy and well-being after adaptation phase
Top reported issues
- Marked increase in appetite, particularly during the first weeks
- Water retention / bloated appearance
- Lethargy and daytime somnolence (especially initially)
- Numbness in the hands (carpal tunnel-like)
- High cost and uncertain product quality from grey-market sources
Significant quality variability in freely available products; contamination and inaccurate dosage labeling have been documented [s11, c4]. Long-term safety unknown; insulin resistance is recognized as a relevant risk by experienced users. The community is increasingly discussing legal risks in Germany and the DACH region [c3, c4]. Some users report depressive mood or anxiety, which could mechanistically be associated with chronic GHS-R1a activation [s9, c1].
Scientific Sources
- Ibutamoren - Wikipedia
Wikipedia contributors (2024). WikipediaCLink - MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism
Murphy MG, Bach MA, Plotkin D, et al. (1998). Journal of Clinical Endocrinology & MetabolismAPMID:9467534 - Is MK-677 Legal? Ibutamoren FDA Status & Legal Guide 2026
Telehealth Ally Editorial Team (2025). telehealthally.comBLink - Ibutamoren — Doping-Lexikon, Deutsche Sporthochschule Köln
DSHS Köln Institut für Biochemie (2024). dshs-koeln.deBLink - Ibutamoren MK677 — Rechtsstatus Deutschland
Diverse Autoren (2025). nnbgkt.info / bmvgig.guruCLink - Pharmacological targeting of age-related changes in skeletal muscle tissue
Sakuma K, Yamaguchi A (2020). PMC / Ageing Research ReviewsBLink - Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Xing C, Qu Q, Jiang H, et al. (2021). Nature CommunicationsCDOI - Growth Hormone Secretagogues as Potential Therapeutic Agents to Restore Growth Hormone Secretion in Older Subjects
Nass R, et al. (2023). Journals of Gerontology: Series ABLink - Performance Enhancing Substance: MK-677 (Ibutamoren)
OPSS / U.S. Department of Defense (2024). opss.orgBLink - Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML, MK-677 Protocol 30 Study Group (2008). NeurologyAPMID:19015485DOI - Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Xing C, Qu Q, Jiang H, et al. (2021). Nature CommunicationsCDOI - Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized Trial
Nass R, Pezzoli SS, Oliveri MC, et al. (2008). Annals of Internal MedicineAPMID:18981485DOI - MK-677 Half Life — Understanding Ibutamoren Dosing
Real Peptides Editorial Team (2024). realpeptides.coCLink - Major Approaches: The Use of GH Secretagogue (MK-677) for Muscle Mass Gain in Elderly — A Brief Systematic Review
Authorea Authors (2021). Authorea PreprintsBLink - Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man
Copinschi G, Leproult R, Van Onderbergen A, et al. (1997). NeuroendocrinologyAPMID:9349662 - Beyond the Hype: Potential Health Risks of MK-677
Get Smart About Drugs / DEA Educational Foundation (2025). getsmartaboutdrugs.govBLink - MK-677: Risks, Research, and Safer Alternatives
BodySpec Editorial Team (2024). bodyspec.comCLink - MK-677 And Cancer: How Strong Is The Evidence?
MediSearch Editorial Team (2024). medisearch.ioCLink
Community Sources
Storage
Unopened
Store at room temperature (15–25 °C), dry and protected from light.
Opened
Keep sealed; avoid moisture for capsule forms; store powder tightly closed at room temperature.
Notes
Commercial MK-677 products from the grey market are not regulated with respect to purity and dosing accuracy. Significant discrepancies between declared and actual active ingredient content have been reported [s11, c4].