THE 30-SECOND OVERVIEW
At a glance
MK-677 is unusual among the compounds sold for growth-hormone research in one respect: its dose is not a convention borrowed from forums. It is a figure that appears, almost unchanged, across two decades of randomised trials. That makes the question easier to answer and, at the same time, easier to misread, because a trial dose is a study design choice, not a recommendation.
What MK-677 is
MK-677, also called ibutamoren or MK-0677, is an orally active small molecule that mimics ghrelin at the growth hormone secretagogue receptor GHS-R1a. It is not a peptide. It reaches the pituitary through the gut rather than a needle, which is the whole reason it was developed, and it is why the published dosing is expressed in plain milligrams by mouth rather than in units per kilogram of an injected solution.
We stock it in two oral formats: a measured MK-677 liquid at 25mg per mL, and MK-677 tablets at 15mg each. Both are for laboratory research only.
The dose the trials converged on
The first dose-ranging work was Chapman and colleagues in 1996. Thirty-two healthy adults aged 64 to 81 received placebo or 2, 10 or 25mg of MK-677 once daily, in study periods of 14 and 28 days. The response was dose-dependent. At 25mg, mean 24-hour growth hormone concentration rose 97 percent, and serum IGF-1 climbed from 141 to 219 micrograms per litre at two weeks and 265 at four weeks, which the authors described as the normal range for young adults. The 2mg and 10mg groups moved less.
That 25mg figure then became the default. Copinschi's group used 5 and 25mg at bedtime for seven days in young men (1996) and 2, 5 and 25mg in the sleep study that followed (1997). Svensson used 25mg daily for eight weeks in obese men (1998). Murphy used 25mg daily for seven days during caloric restriction (1998), and 10 or 25mg in elderly bone-marker studies, with one arm stepping from 25 to 50mg (1999). Nass used 25mg once daily for two years in healthy older adults (2008). Both hip-fracture trials, Bach (2004) and Adunsky (2010), used 25mg a day. The 563-patient Alzheimer's trial used 25mg daily for 12 months (Sevigny, 2008).
So the honest summary is that the adult research record is a 25mg once-daily record, with a small amount of 2 to 10mg dose-ranging data underneath it and one brief excursion to 50mg.
Weight-based dosing in children
The paediatric work is the exception, and it is expressed per kilogram. Codner and colleagues (2001) gave 18 prepubertal children with growth hormone deficiency 0.2mg per kg per day for seven days, or 0.8mg per kg per day for seven to eight days. At the higher amount, median peak growth hormone rose 3.8 micrograms per litre and IGF-1 rose 12 micrograms per litre from baseline, with no change in prolactin, glucose, thyroid hormones, cortisol or insulin over that short window.
The same compound was later taken forward as LUM-201 for paediatric growth hormone deficiency. Bright and colleagues (2021, 2022) reported on a 68-child randomised trial and on a single-dose stimulation test in which LUM-201 produced a median peak growth hormone of 15.0 nanograms per mL against 5.5 for standard diagnostic stimuli. That programme is ongoing and its dosing sits outside the adult figure above.
Once daily, and often at bedtime
Two design choices recur alongside the 25mg number. The first is once-daily administration, which follows from the pharmacology: a single oral dose in the Chapman study raised growth hormone by amplifying the pulses that were already there, increasing pulse height and the trough between pulses without changing how many pulses occurred.
The second is timing. Copinschi's studies gave the drug at bedtime, because growth hormone secretion concentrates in the first hours of sleep. In the 1997 sleep study, 25mg at bedtime for seven days increased stage IV sleep by roughly 50 percent and REM sleep by more than 20 percent in young adults, and increased REM by nearly 50 percent in adults aged 65 to 71 over 14 days. A study that ignores timing is discarding a variable the mechanism says matters.
What 25mg produced, and what it did not
The IGF-1 response is consistent. Increases of roughly 40 percent in obese men (Svensson, 1998), 55 to 94 percent in elderly subjects (Murphy, 1999), 84 percent in hip-fracture patients (Bach, 2004), 60 to 73 percent in the Alzheimer's cohort (Sevigny, 2008) and 65 percent above placebo in haemodialysis patients (Campbell, 2018) all came from the same once-daily figure.
The clinical outcomes are less consistent, and that matters for anyone reading the dose as a promise. In the two-year Nass trial, fat-free mass rose 1.1kg against a 0.5kg decline on placebo, yet strength and function did not change. Both hip-fracture trials raised IGF-1 substantially without a statistically significant improvement in most functional measures, and the 2010 trial was stopped early over a heart-failure signal in a small number of patients. The Alzheimer's trial showed target engagement and no effect on progression. A dose can be pharmacologically effective and clinically inconclusive at the same time.
The trials also recorded costs. Chapman saw fasting glucose rise from 5.4 to 6.8 mmol per litre at four weeks. Svensson found fasting glucose unchanged but an impaired oral glucose tolerance test at two and eight weeks. Nass reported a 0.3 mmol per litre rise in fasting glucose, reduced insulin sensitivity, an appetite increase that faded over a few months, and transient mild oedema and muscle pain. Our companion article on what the trials recorded as side effects goes through these one by one.
Converting a research figure to a laboratory amount
If a protocol reproduces a published quantity, the arithmetic depends on format. The MK-677 liquid is 25mg per mL, so 25mg is 1.0mL, 10mg is 0.4mL, 5mg is 0.2mL and 2mg is 0.08mL, drawn with a calibrated pipette or dropper. The 15mg tablets are pre-measured, which suits a fixed-amount design and does not suit a dose-ranging one. These are concentration calculations, not recommendations, and nothing here describes a route or schedule for human use.
What the research does not establish
The 25mg record is almost entirely adults over 60, obese men, and patients. Healthy young adults appear only in the seven-day Copinschi crossovers. Nothing in the published record characterises the compound in the populations it is most often discussed for.
There is no dose-response work above 25mg beyond the two-week 50mg arm in Murphy's bone-marker study, so the shape of the curve past that point is unknown.
And the longest exposure is two years, in 65 people. Every question about longer use is open.
The takeaway
MK-677 has one of the most consistent dosing records in the secretagogue literature: 25mg once daily by mouth, often at bedtime, across trials from 1996 to 2018, with weight-based figures in children. The record is strong on what the dose does to growth hormone and IGF-1 and weak on what that translates into. Read it as a description of study designs, not as a protocol. For programmes that compare it with peptide secretagogues, MK-677 vs ipamorelin covers the receptor they share.
All products are intended for research use only. Not for human consumption. Must be 21 years of age or older to purchase.
References
1. Chapman, I. M., Bach, M. A., Van Cauter, E., et al. (1996). 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 subjects. Journal of Clinical Endocrinology and Metabolism, 81(12), 4249-4257.
2. Copinschi, G., Van Onderbergen, A., L'Hermite-Balériaux, M., et al. (1996). 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 men. Journal of Clinical Endocrinology and Metabolism, 81(8), 2776-2782.
3. Copinschi, G., Leproult, R., Van Onderbergen, A., et al. (1997). Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology, 66(4), 278-286.
4. Murphy, M. G., Plunkett, L. M., Gertz, B. J., et al. (1998). MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. Journal of Clinical Endocrinology and Metabolism, 83(2), 320-325.
5. Svensson, J., Lönn, L., Jansson, J. O., et al. (1998). Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. Journal of Clinical Endocrinology and Metabolism, 83(2), 362-369.
6. Murphy, M. G., Bach, M. A., Plotkin, D., et al. (1999). Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. Journal of Bone and Mineral Research, 14(7), 1182-1188.
7. Codner, E., Cassorla, F., Tiulpakov, A. N., et al. (2001). Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children. Clinical Pharmacology and Therapeutics, 70(1), 91-98.
8. Bach, M. A., Rockwood, K., Zetterberg, C., et al. (2004). The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. Journal of the American Geriatrics Society, 52(4), 516-523.
9. Nass, R., Pezzoli, S. S., Oliveri, M. C., et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9), 601-611.
10. Sevigny, J. J., Ryan, J. M., van Dyck, C. H., et al. (2008). Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology, 71(21), 1702-1708.
11. Adunsky, A., Chandler, J., Heyden, N., et al. (2011). 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, 53(2), 183-189.
12. Campbell, G. A., Patrie, J. T., Gaylinn, B. D., Thorner, M. O., & Bolton, W. K. (2018). Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study. Nephrology Dialysis Transplantation, 33(3), 523-530.
13. Bright, G. M., Do, M. T., McKew, J. C., Blum, W. F., & Thorner, M. O. (2021). Development of a predictive enrichment marker for the oral GH secretagogue LUM-201 in pediatric growth hormone deficiency. Journal of the Endocrine Society, 5(6), bvab030.
14. Bright, G. M., & Thorner, M. O. (2022). A GH secretagogue receptor agonist (LUM-201) elicits greater GH responses than standard GH secretagogues in subjects of a pediatric GH deficiency trial. Hormone Research in Paediatrics, 95(1), 76-81.
