MK-677 (Ibutamoren)

Growth Hormone Secretagogue (Non-Peptide, Oral GHS)research

Also known as: Ibutamoren, Ibutamoren Mesylate, MK-0677, L-163,191, Nutrobal

An orally active, non-peptide growth hormone secretagogue that mimics ghrelin to raise GH and IGF-1 levels for up to 24 hours per dose, with notable effects on sleep, appetite, and body composition.

Overview

MK-677 (Ibutamoren) is technically not a peptide but a non-peptide, orally bioavailable growth hormone secretagogue that mimics the action of ghrelin by binding to the GHS-R1a receptor. It is included in peptide discussions because it activates the same pathway as peptide GHRPs but can be taken orally rather than injected. MK-677 produces sustained elevation of GH and IGF-1 levels for up to 24 hours after a single oral dose, without significantly affecting cortisol levels. Originally developed by Merck for treatment of GH deficiency, frailty, and osteoporosis, it has been studied in multiple clinical trials but never received FDA approval. It is one of the most popular compounds in the biohacking and bodybuilding communities due to its oral convenience, potent sleep-enhancing properties, and significant effects on body composition. Notable considerations include strong appetite stimulation and potential effects on blood glucose and insulin sensitivity.

Mechanism of Action

MK-677 acts through: (1) Mimicking endogenous ghrelin by binding to the GHS-R1a receptor on pituitary somatotrophs, stimulating GH release; (2) Produces pulsatile GH release pattern, preserving physiological secretion dynamics; (3) Raises IGF-1 levels by 40-90% with sustained use, through increased GH-mediated hepatic IGF-1 synthesis; (4) Does not suppress the hypothalamic-pituitary axis or natural GH production; (5) Activates ghrelin pathways in the hypothalamus, strongly stimulating appetite (orexigenic effect); (6) Increases duration and quality of REM and stage 4 (deep) sleep; (7) Unlike injected GHRPs, bypasses first-pass metabolism issues due to its non-peptide structure.

Molecular Formula

C27H36N4O5S

Molecular Weight

528.66 g/mol

Dosage Protocols

Dose Range

10mg25mg

Frequency

Once daily

Route

oral

Cycle Length

8-12 weeks on, 4 weeks off (or ongoing with monitoring)

Take before bed to enhance deep sleep and coincide with natural nocturnal GH surge. Most users find 15-25mg optimal. Strong appetite stimulation may occur 30-60 minutes after dosing.

Source: Clinical trial data and community protocols

Side Effects

EffectSeverity
Increased appetitemoderate
Water retention / bloatingmild
Lethargy / drowsinessmild
Numbness / tingling in extremitiesmild
Elevated fasting blood glucosemoderate
Insulin resistancemoderate
Joint painmild
Vivid dreamsmild

Pros & Cons

Oral administration — no injections needed, unique among GH secretagogues

Dramatically improves sleep quality, particularly deep sleep stages

Sustained 24-hour GH/IGF-1 elevation from a single daily dose

Extensive clinical trial data in humans (multiple Phase 2 studies)

Does not suppress natural GH production or desensitize the pituitary

Strong appetite stimulation can lead to unwanted weight gain if not managed

Can impair insulin sensitivity and raise fasting blood glucose with chronic use

Water retention and bloating are common, especially in the first few weeks

Not FDA-approved despite extensive clinical research

Effects on blood sugar make it potentially risky for pre-diabetic individuals

Research Studies

Legal Status

Not FDA-approved. Sold as a research chemical. Not scheduled as a controlled substance in most countries. Banned by WADA. Available widely online, but regulatory status varies by jurisdiction.

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