Does MK-677 safely raise growth hormone and build muscle?

What MK-677 is

MK-677, also called ibutamoren, was developed in the 1990s. Researchers described it as an orally active, non-peptide mimic of growth-hormone-releasing peptides, and later as a ghrelin mimetic, because it acts on the same receptor as the natural hunger hormone ghrelin. It is often sold alongside peptides, but chemically it is not one.

A 2018 review of growth hormone secretagogues explained the appeal: unlike injected growth hormone, these drugs prompt the pituitary gland to release its own hormone in pulses that remain subject to the body's normal feedback controls. The same review noted that few long-term, rigorously controlled studies had examined how well these drugs work or how safe they are.

Sources: PubMed 9467534 · PubMed 18981485 · PubMed 28400207

The part that holds up: growth hormone and IGF-1 rise

This is well documented. In a 1996 placebo-controlled trial in 32 healthy adults aged 64 to 81, MK-677 increased 24-hour growth hormone levels in a dose-dependent way by boosting the natural pulses, and at the highest dose tested it brought IGF-1 up into the normal range for young adults within four weeks. In an eight-week trial in 24 obese but otherwise healthy men, IGF-1 rose by about 40% compared with placebo.

Larger and longer trials showed the same effect. In 563 people with Alzheimer's disease, IGF-1 was about 60% higher at six weeks and 73% higher at 12 months. In a small crossover trial in hemodialysis patients, IGF-1 rose 65% more on MK-677 than on placebo. So the hormone-raising part of the claim is supported.

Sources: PubMed 8954023 · PubMed 9467542 · PubMed 19015485 · PubMed 28340044

More lean mass, but not more strength

The best test of the muscle claim is a two-year, placebo-controlled trial of 65 healthy adults aged 60 to 81, published in 2008. After one year, fat-free mass fell by 0.5 kg on placebo and rose by 1.1 kg on MK-677. But the increase in fat-free mass did not lead to any change in strength or physical function. Body weight rose more on MK-677, and so did fat in the arms and legs. The authors noted that the study was too small and short to judge functional outcomes properly.

Shorter trials point the same way. Fat-free mass increased in obese men over eight weeks while total and abdominal fat did not change, and in eight healthy volunteers on a calorie-restricted diet, a week of MK-677 reversed nitrogen loss, a sign of protein breakdown. Fat-free mass counts everything that is not fat, including water, so it is not a direct measure of muscle, and none of these studies tested people who were training to build muscle.

Sources: PubMed 18981485 · PubMed 9467542 · PubMed 9467534

When it was tested on real-world outcomes

MK-677 has been tested against clinical goals several times, with disappointing results. In a 2004 trial of 161 older adults recovering from hip fracture, IGF-1 rose by 84% on MK-677 compared with 17% on placebo, but there were no significant differences in physical function or daily living measures. A second hip-fracture trial in 123 older patients found a small improvement in gait speed but no improvement in most other function tests, and it was stopped early because of a safety signal of congestive heart failure in a small number of patients. The authors concluded that MK-677 has an unfavorable safety profile in this group.

In the 563-person Alzheimer's trial, a year of treatment did not slow disease progression on any measure, despite the large rise in IGF-1. In 292 postmenopausal women with low bone density, adding MK-677 to the osteoporosis drug alendronate improved bone density more than alendronate alone only at the femoral neck of the hip, not at the spine or other sites, and growth hormone-related side effects were noted.

Sources: PubMed 15066065 · PubMed 21067829 · PubMed 19015485 · PubMed 11238495

The safety signals

In the two-year trial in healthy older adults, fasting blood sugar rose and insulin sensitivity fell on MK-677. The most common side effects were increased appetite, which faded after a few months, and mild, temporary swelling of the lower legs and muscle pain. Cortisol levels also rose. In the eight-week trial in obese men, a glucose tolerance test showed worse glucose handling, and in the four-week trial in older adults, fasting glucose increased.

The 2018 review highlighted the blood sugar concern and said that the safety of long-term use, including cancer rates and death, still needs to be studied. A 2025 case report described liver inflammation in a healthy man in his early 30s who had been using MK-677 as a supplement for about two months. His liver tests returned to normal after he stopped. A single case cannot show cause, but it is a reminder that unsupervised use falls outside anything the trials examined.

Sources: PubMed 18981485 · PubMed 9467542 · PubMed 8954023 · PubMed 28400207 · PubMed 40675653

What regulators and sport say

The FDA has placed ibutamoren mesylate on its list of bulk substances that may present significant safety risks in compounding. It states that the drug poses significant safety risks because of the potential for congestive heart failure in certain patients, and it cites the hip-fracture trial that was terminated early for that reason.

The World Anti-Doping Agency names ibutamoren (MK-677) among growth hormone secretagogues that are prohibited at all times. Taken together, the evidence supports the idea that MK-677 raises growth hormone and lean mass, but not that it builds functional muscle or that it is safe for unsupervised long-term use.

Sources: fda.gov · PubMed 21067829 · wada-ama.org

Profiles

MK-677 profile →

References

1. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab · 1998 · PMID 9467534
2. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med · 2008 · PMID 18981485
3. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev · 2018 · PMID 28400207
4. 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. J Clin Endocrinol Metab · 1996 · PMID 8954023
5. Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab · 1998 · PMID 9467542
6. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology · 2008 · PMID 19015485
7. Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study. Nephrol Dial Transplant · 2018 · PMID 28340044
8. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc · 2004 · PMID 15066065
9. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr · 2011 · PMID 21067829
10. Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab · 2001 · PMID 11238495
11. Hepatotoxicity induced by MK-677. BMJ Case Rep · 2025 · PMID 40675653

Other sources

• https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
• https://www.wada-ama.org/en/prohibited-list

These are original summaries of published research, written with AI assistance and checked against the cited sources. They are not medical advice and have not been reviewed by a clinician. Every PubMed reference was checked against PubMed's record for title, year and journal. All claim checks · Editorial standards