Ibutamoren (MK-677)

Ibutamoren, also known as MK-677, is a non-peptide compound that mimics the action of ghrelin, a naturally occurring hormone that stimulates growth hormone release. Unlike peptides, it is a small molecule and does not contain amino acids. It was originally developed to increase growth hormone and insulin-like growth factor 1 (IGF-1) levels in the body.

Its purported benefits include promoting muscle growth, improving bone density, enhancing recovery, and supporting better sleep quality. Some studies also suggest it may help increase appetite and improve body composition by increasing lean mass while reducing fat.

The compound Ibutamoren (MK-677) has been shown in human and animal studies to stimulate the release of growth hormone (GH) and increase insulin-like growth factor 1 (IGF-1) levels. For example, in a caloric-restriction human trial, MK-677 improved nitrogen balance compared with placebo, indicating reduced protein catabolism ¹. In a 12-month randomized trial in older adults, MK-677 enhanced pulsatile GH secretion and increased fat-free mass (lean body mass) ². These findings indicate that MK-677’s main physiological effect is to elevate GH/IGF-1 and support lean mass accrual under certain conditions.

Beyond hormone levels, MK-677 has been found to improve body composition by increasing fat-free mass in older adults. In the 12-month trial it significantly increased lean body mass, though it did not show strong evidence of improved muscle strength or functional performance ³. Animal studies suggest limited growth-plate or long-term height benefit after several weeks of dosing, indicating effects may be context-specific ⁴. In sum, the main benefits of MK-677 appear to include enhanced GH/IGF-1 secretion and resultant increases in lean body mass under selected conditions.

The compound Ibutamoren (MK‑677) has been associated with adverse metabolic and hormonal effects in clinical studies. In a trial involving older adults, fasting blood glucose increased by about 0.3 mmol/L and insulin sensitivity declined during use ⁵. Another study in obese males found that glucose homeostasis was impaired during treatment with MK-677 for eight weeks ⁶. Thus one of the main negative effects is its impact on glucose metabolism and insulin responsiveness.

Additional reported side effects include increased appetite, fluid retention, and elevated bone turnover markers. In one human trial, increased appetite and mild lower extremity edema and muscle pain were reported ⁷. Other evidence from elderly adults showed increased markers of bone resorption and bone formation with MK-677 administration ⁸. In sum, the main negative side effects of MK-677 include impaired glucose metabolism, increased hunger and fluid retention, and elevated bone turnover.

Ibutamoren (MK-677) functions primarily by acting as an agonist at the ghrelin receptor (GHS-R1a) in the hypothalamus and pituitary, which mimics the hormone ghrelin and triggers increased secretion of growth hormone (GH). In human trials, oral MK-677 elevated 24-hour GH concentrations by nearly 100 % in older adults and increased serum insulin‑like growth factor 1 (IGF-1) into young-adult ranges ⁹. Once GH is elevated it stimulates downstream production of IGF-1 (primarily by the liver) which mediates many of the anabolic and growth-related effects. Animal work also shows that sustained administration may induce compensatory increases in hypothalamic somatostatin expression, which can blunt GH responsiveness over time ¹⁰.

Ibutamoren is not approved by the Food and Drug Administration (FDA) for human therapeutic use. It has been identified as an investigational compound. For example, FDA warned that a product contained ibutamoren which is “an active ingredient not approved by FDA … safety and efficacy have not been established ¹¹." In sports, the World Anti‐Doping Agency (WADA) includes ibutamoren (MK‑677) in its Prohibited List under section S2 (Peptide hormones, growth factors, related substances & mimetics) as an example of a growth hormone secretagogue (GHS) ¹².