MK-677
Ibutamoren · Ibutamoren mesylate · MK-0677 · L-163,191 · Nutrobal
Oral ghrelin mimetic that raises GH and IGF-1 for a full 24 hours from one daily dose.
Typical dose
10 mg
Once daily
Range
5–25
mg
Half-life
6 h
see Dosing
Evidence
Human trials
Oral
What it is
MK-677 is not a peptide. It is an orally active non-peptide molecule that mimics ghrelin at the growth hormone secretagogue receptor, and it is the only compound in this section that reliably raises GH and IGF-1 without an injection.
The human data is unusually good for something sold as a research chemical. In a two-year randomised trial in healthy older adults, 25 mg daily restored IGF-1 to young-adult levels and added roughly 1 kg of fat-free mass over the first year. The same trial supplies the main caution: insulin sensitivity declined and mean fasting glucose rose by about 5 mg/dL.
The two effects everyone notices are appetite and sleep. Hunger can be severe and is the single most common reason people quit; deeper slow-wave sleep is the most common reason they stay. Separately, a Phase 2b hip-fracture trial was stopped early over a congestive heart failure signal in frail elderly patients, which is worth knowing even though that population does not map neatly onto healthy trainees.
How it works
MK-677 binds GHS-R1a in the pituitary and hypothalamus, the same receptor ghrelin uses. It amplifies natural GH pulses rather than replacing them, so release stays pulsatile and the pituitary's own feedback loops remain intact. That is why it does not shut the axis down the way injected GH does and why it needs no recovery period after stopping.
Because it acts on a different receptor from GHRH analogues such as CJC-1295 or sermorelin, the two combine additively. Combining it with a GHRP such as ipamorelin or GHRP-2 does not, since those compete for the same receptor.
Dosing
25 mg is the trial dose and also the point where appetite, fluid retention and glucose drift become hardest to manage. Most people capture the bulk of the IGF-1 response at 10-12.5 mg with far fewer side effects.
Preparation
OralMK-677 is taken orally — there is nothing to reconstitute, so the dosing calculator does not apply.
Oral compound, so there is nothing to reconstitute. It is sold as capsules or as a liquid in an ethanol or PEG carrier; liquid concentrations vary widely between vendors, so confirm the stated mg per mL before dosing by dropper.
Storage
Sealed
Powder and capsules keep for years cool, dry and out of direct light at normal room temperature.
Once opened
Liquid preparations are fine at room temperature unopened, but refrigerate after opening and use within a few months. Alcohol and PEG carriers degrade with heat and light.
Reported benefits
- ▪Raises GH and IGF-1 substantially with no injections
- ▪Noticeably deeper slow-wave sleep for most users
- ▪Increases fat-free mass, around 1 kg over a year at 25 mg under trial conditions
- ▪Strong appetite stimulation, useful in a bulk or for anyone who struggles to eat enough
- ▪Preserves pulsatile release and does not suppress the natural GH axis
- ▪Backed by genuine randomised human trials, including a two-year study
Side effects
- ▪Appetite increase that many people find difficult to control
- ▪Fluid retention with a puffy face and hands, and rapid scale weight that is not tissue
- ▪Falling insulin sensitivity and rising fasting glucose, the clearest documented risk
- ▪Lethargy and morning grogginess, particularly with pre-bed dosing
- ▪Numbness or tingling in the hands, from fluid rather than nerve injury
- ▪Vivid dreams and, for a minority, disrupted rather than improved sleep
- ▪A congestive heart failure signal ended a trial early in frail elderly hip-fracture patients
Do not use if
- ▪Type 2 diabetes, prediabetes or significant existing insulin resistance
- ▪Active malignancy or recent cancer history, given the sustained IGF-1 elevation
- ▪Existing congestive heart failure or significant cardiac disease
- ▪Untreated sleep apnoea, which fluid retention and soft-tissue growth can worsen
Evidence level — Human trials
Controlled human clinical data exists.
Never approved for human use, sold as a research chemical, banned in sport by WADA, and not a lawful dietary supplement ingredient in the United States.
Commonly run with
CJC-1295 with DAC
Albumin-binding GHRH analogue that lifts GH and IGF-1 for days from one injection.
1000 mcg · 1-2x weekly
CJC-1295 no-DAC
Short-acting GHRH fragment that sharpens one GH pulse, almost always run with a GHRP.
100 mcg · 1-3x daily
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
MK-677 FAQ
Does MK-677 need to be cycled?+
Not for hormonal recovery, since it does not suppress the GH axis. The reason to take breaks is metabolic: fasting glucose and insulin sensitivity drift the wrong way over months. Running 8-16 week blocks and checking fasting glucose or HbA1c in between is the sensible compromise.
Why did I gain 5 kg in two weeks?+
Water and food. MK-677 causes real fluid retention and a large appetite increase, and both hit hardest in the first fortnight. Judge it on how you look and how your lifts move at week 8, not on the scale at week 2.
Can I stack it with ipamorelin or GHRP-2?+
There is little point. MK-677 and the GHRPs are all agonists at the same GHS-R1a receptor, so they compete rather than add. Stacking with a GHRH analogue such as CJC-1295 or sermorelin does make sense, because that is a separate receptor and the two amplify each other.
Is the blood sugar risk overstated?+
No. In the two-year trial, insulin sensitivity fell and mean fasting glucose rose by about 5 mg/dL in healthy older adults at 25 mg. That is small on average, but the average hides individuals who moved a lot. If you already sit near the prediabetic range, this is the wrong compound.
Morning or night?+
Either. Pre-bed is traditional because of the sleep effect, but the roughly 24-hour duration means timing barely changes the IGF-1 response. People who wake groggy or ravenous usually do better moving the dose to the morning.
References
- 1.Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial — Annals of Internal Medicine (2008) PMID 18981485
- 2.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 — Journal of Clinical Endocrinology and Metabolism (1996) PMID 8954023
- 3.MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study — Archives of Gerontology and Geriatrics (2011) PMID 21067829
More gh secretagogues
CJC-1295 no-DAC
Short-acting GHRH fragment that sharpens one GH pulse, almost always run with a GHRP.
100 mcg · 1-3x daily
CJC-1295 with DAC
Albumin-binding GHRH analogue that lifts GH and IGF-1 for days from one injection.
1000 mcg · 1-2x weekly
GHRP-2
Potent, well-studied GHRP with a bigger pulse than ipamorelin and more cortisol.
100 mcg · 2-3x daily
GHRP-6
The original GHRP: solid GH release and the strongest hunger response of the group.
100 mcg · 2-3x daily