MK-677 (Ibutamoren)
MK-677 (Ibutamoren) scored 4.8 / 10 (⚖️ Neutral) on the BioHarmony scale as a Substance → Research Compound.
MK-677 (ibutamoren) is an oral, once-daily growth-hormone secretagogue that raises IGF-1 by about 50 to 97 percent and adds roughly 1.1 kg of fat-free mass, per the Nass 2008 two-year trial, but it also raises fasting glucose and never won FDA approval.
What is MK-677 (Ibutamoren)?
MK-677, also called ibutamoren, is an oral, once-daily growth-hormone secretagogue that lands at a Neutral 4.8 because its real strengths and real harms almost perfectly cancel out. It works by activating the ghrelin receptor, which nudges your own pituitary to release more growth hormone and raises IGF-1 into the young-adult range, per Patchett 1995. What makes it stand out from the injectable peptides people compare it to is the evidence behind it. It has been through multiple double-blind, placebo-controlled human trials, including a 2-year study and a 563-patient pivotal trial. That is far more human data than most things in this category have.
Here is the honest tension, and it runs through this whole report. The deep evidence base is exactly what should make MK-677 attractive, but most of that evidence is bad news. It reliably raises the hormones it is supposed to raise. It just kept failing to turn that into anything you would actually feel. The lean mass it builds did not improve strength. The disease trials it ran flopped. And it carries a metabolic cost that shows up every single time. So this is not a hyped peptide with no data. It is a well-studied drug whose own studies are the reason to be cautious.
Terminology
A few terms decide how you read this report, because MK-677 gets mislabeled constantly and because the gap between "the hormone went up" and "the outcome improved" is the whole story here.
- Growth-hormone secretagogue: A compound that prompts your body to release its own growth hormone, rather than injecting growth hormone directly. MK-677 is one.
- GHS-R1a: The growth-hormone-secretagogue receptor, also called the ghrelin receptor. This is what MK-677 activates, which is also why it stimulates appetite.
- IGF-1: Insulin-like growth factor 1. The downstream signal growth hormone produces. It is the marker users track and the pathway behind the cancer caution.
- Fat-free mass: Everything in your body that is not fat, including muscle and water. A rise in fat-free mass is not the same as a strength gain, a distinction that matters a lot for MK-677.
- SARM: Selective androgen receptor modulator. MK-677 is often sold alongside SARMs and mislabeled as one, but it is not a SARM. It does not act on androgen receptors at all.
- Insulin sensitivity: How well your cells respond to insulin to clear glucose. MK-677 lowers it, which is the core metabolic problem.
- Edema: Fluid retention and swelling. The basis of the puffy "MK bloat" look people report.
How do you take MK-677 (Ibutamoren)?
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 1 route and 4 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| Oral | Tablet or capsule, taken once daily, often pre-sleep | No approved clinical dose; every efficacy trial used 25 mg once daily | 10 to 25 mg once daily |
Protocols
Conservative starter Anecdotal
- Dose
- 10 to 12.5 mg
- Frequency
- Once daily, pre-sleep
- Duration
- 8 to 12 weeks
The low-and-slow entry point. Most people start here to soften the hunger spike and the puffy water-retention look before deciding whether to go higher. Not an approved dose.
Standard trial-matched Mixed
- Dose
- 25 mg
- Frequency
- Once daily, pre-sleep
- Duration
- 8 to 16 weeks, then a break
Matches the dose used in every published efficacy trial, including Nass 2008 and Sevigny 2008. Pre-sleep timing aligns the growth-hormone pulse with natural nocturnal secretion and leans on the sleep data. Not an approved dose.
Cycled block Anecdotal
- Dose
- 10 to 25 mg
- Frequency
- Once daily, or 5 days on and 2 off
- Duration
- 8 to 16 week blocks with breaks
Cycling is a community heuristic to limit glucose drift, appetite, and water retention. There is no clinical basis for any particular on-off schedule. Not an approved dose.
Morning-dose variant Anecdotal
- Dose
- 10 to 25 mg
- Frequency
- Once daily, morning
- Duration
- 8 to 16 weeks
Some users move the dose to the morning to avoid next-day grogginess or the puffy water-retention look on waking. No head-to-head timing trial exists. Not an approved dose.
How this score is calculated →
What are the benefits of MK-677 (Ibutamoren)?
Upside contribution: 2.28
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 3.4 | 0.850 | |
| Breadth | 15% | 3.2 | 0.480 | |
| Evidence | 25% | 3.7 | 0.925 | |
| Speed | 10% | 3.4 | 0.340 | |
| Durability | 10% | 2.0 | 0.200 | |
| Bioindividuality | 15% | 3.2 | 0.480 | |
| Total | 3.275 |
Upside Rationale
The upside comes from one genuinely strong place and several merely plausible ones. The strong place is evidence: MK-677 has more real human trial data than anything else in the growth-hormone-secretagogue class, and that data reliably shows it raising IGF-1 and adding lean mass. The strongest single result is the 2-year frailty trial, which added about 1.1 kg of fat-free mass over a year, per Nass 2008. The key boundary, which I will keep returning to, is that the biomarker and body-composition wins repeatedly did not become functional wins. So the upside is real but shallow: it does what it says to your hormones and your scale, with thin proof that this matters for how you feel or perform.
Efficacy (3.4/5.0): Efficacy is mid-high because the biomarker and body-composition effects are real and replicated, while the functional payoff is missing. The 2-year Nass 2008 trial in 65 older adults raised IGF-1 into the young-adult range and added about 1.1 kg of fat-free mass versus a small loss on placebo, with body weight up 2.7 kg. Earlier work in healthy elderly showed 25 mg per day lifting 24-hour growth hormone about 97 percent, per Chapman 1996. Those are solid, repeatable effects on the things MK-677 targets. The reason it does not score higher is that the same frailty trial found the added lean mass did not change strength or function, and every disease endpoint failed. It is a reliable biomarker mover, not a proven outcome mover.
Breadth of Benefits (3.2/5.0): Breadth is moderate because the growth-hormone axis touches several systems, even if proof thins out fast. The documented effects span lean mass and body composition, per Nass 2008, deeper sleep, per Copinschi 1997, and bone remodeling, per Svensson 1998. It also showed an anti-catabolic, nitrogen-sparing effect during caloric restriction in a separate crossover study. That is genuine mechanistic reach. The limit is that the disease-specific bets, frailty function, Alzheimer's, and hip-fracture recovery, all failed or were halted, so the breadth of real benefit is narrower than the breadth of mechanism. Wide net, modest catch.
Evidence Quality (3.7/5.0): Evidence is MK-677's signature strength and the reason it out-scores its peptide peers. It has multiple double-blind, placebo-controlled human RCTs, including a 2-year trial in 65 adults, per Nass 2008, and a 563-patient pivotal Alzheimer's study, per Sevigny 2008. Compare that to ipamorelin or the CJC-1295 peptides, which rest mostly on mechanism, small studies, and anecdote. The score is held below the top because the trial program was Merck-funded and, more importantly, because the outcomes were consistently negative. High-quality evidence that mostly says "this did not work" is still high-quality evidence, and that is what lifts this dimension while capping the overall score.
Speed of Onset (3.4/5.0): Speed is a relative strength on biomarkers and slower on the physique. Growth hormone rises within hours of the first dose, with peak GH of 55.9 micrograms per liter on day one, per Murphy 1998. Sleep changes show up within roughly a week, per Copinschi 1997, and IGF-1 plateaus over two to four weeks. The body-composition shift, the thing most people are actually after, takes months to become visible. So the hormonal action is fast, the felt effects are medium, and the look-in-the-mirror change is slow.
Durability (2.0/5.0): Durability is low, because this is a maintain-to-keep-it tool. The effect is reversible receptor activation, so once you stop, growth hormone and IGF-1 normalize within weeks and most of the lean-mass gain washes out. The Nass trial dosed continuously for the full 2 years precisely because the benefit depends on ongoing dosing. There is no published evidence of a durable, drug-free benefit after a cycle ends. You keep the results only as long as you keep taking it.
Bioindividuality Upside (3.2/5.0): Response varies more in tolerability than in efficacy. The IGF-1 rise is fairly consistent across people in the trials, so most users will move the biomarker. What varies widely is how they handle it: appetite surge, water retention, grogginess, and glucose drift hit some people hard and barely touch others. Older adults with lower baseline growth hormone tend to notice more, while the side-effect load is what usually decides whether someone stays on or doses down. So the predictable part is the hormone response, and the unpredictable part is whether you tolerate getting it.
What are the risks & downsides of MK-677 (Ibutamoren)?
Downside contribution: 2.50 (safety risks weighted extra)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety | 30% | 3.3 | 0.990 | |
| Side effects | 15% | 3.3 | 0.495 | |
| Cost | 5% | 2.4 | 0.120 | |
| Effort | 5% | 1.8 | 0.090 | |
| Opportunity | 5% | 3.0 | 0.150 | |
| Dependency | 15% | 3.0 | 0.450 | |
| Reversibility | 25% | 2.2 | 0.550 | |
| Total | 2.845 | |||
| Harm subtotal × 1.4 | 3.479 | |||
| Opportunity subtotal × 1.0 | 0.360 | |||
| Combined downside | 3.839 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 2.499 |
Downside Rationale
The downside is dominated by intrinsic harm, not by cost or hassle, and that harm is what cancels the evidence advantage. The dominant cluster is metabolic: MK-677 raises fasting glucose and lowers insulin sensitivity in every long study, which is a certainty rather than a risk. On top of that sit common edema and appetite effects, and one serious congestive-heart-failure signal that halted a Merck trial, per Adunsky 2011. The people most exposed are anyone pre-diabetic, anyone with cardiac history, and anyone with cancer risk, since IGF-1 is mitogenic. The concerns are mostly intrinsic to the mechanism, which is why they show up so reliably, and they are the reason a well-evidenced drug still lands only at Neutral.
MK-677 grows lean tissue that the body does not seem able to use. The increased fat-free mass did not result in changes in strength or function, the very thing the frailty program was built to prove. Nass 2008
Safety Risk (3.3/5.0): Safety risk is meaningful and built from three layers. First, certain metabolic harm: fasting glucose rose from 5.4 to 6.8 mmol per liter at four weeks, per Chapman 1996, and insulin sensitivity fell over one to two years, per Nass 2008. Second, common but mild edema and appetite effects. Third, and most serious, a congestive-heart-failure signal that terminated a hip-fracture Phase IIb early, with the authors calling the safety profile unfavorable, per Adunsky 2011. That signal hit frail, comorbid elderly patients, so it may not fully generalize to healthy users, which is why this sits at 3.3 rather than higher. But a fluid-retaining drug that stressed weak hearts enough to stop a trial earns real caution. Absolute contraindications: heart failure, active cancer, and poorly controlled diabetes.
Side Effect Profile (3.3/5.0): Side effects are common, dose-related, and the usual reason people quit or dose down. The big three are a sharp appetite surge, water retention and facial puffiness known as MK bloat, and grogginess or lethargy, especially at 25 mg. The Nass 2008 trial listed increased appetite and transient mild lower-limb edema as the most frequent effects. Carpal-tunnel-type tingling from fluid pressure also appears. Most of these are reversible and fade or respond to a lower dose, but they are frequent enough to drive real-world discontinuation.
Financial Cost (2.4/5.0): Cost is low to moderate and ongoing for ibutamoren. Grey-market research-chemical ibutamoren is generally cheaper per month than branded injectable peptides, and the oral format avoids needles and supplies. The real cost is that you are paying for unregulated, often unverified product, and you should add third-party testing plus periodic glucose and IGF-1 labs to the budget. Not expensive per dose; the recurring spend on an unapproved compound is the framing.
Time/Effort Burden (1.8/5.0): Effort is MK-677's clearest advantage. It is an oral tablet or capsule taken once a day, with no reconstitution, no injections, no cold-chain storage, and no fasted-timing rituals. That is a major convenience edge over every injectable peptide in this category. The only real friction is sourcing verified product and remembering a daily dose.
Opportunity Cost (3.0/5.0): Opportunity cost is genuine because better-validated options exist for the same goals. Tesamorelin is FDA-approved with a cleaner metabolic profile where its indication applies, per Falutz 2007. For body composition and function, resistance training, protein, and sleep move the same outcomes with far more certainty and no glucose penalty. Money, attention, and a tolerated glucose hit spent on an outcome-failed, non-approved drug could go to levers with proven returns. That trade-off is the opportunity cost.
Dependency/Withdrawal (3.0/5.0): Dependency is functional, not addictive. There is no craving or withdrawal syndrome, but the benefit persists only while you dose, so stopping returns you to baseline. That is reliance on continued use to hold any gain, similar to other growth-hormone-axis tools. The lack of a true withdrawal pattern keeps this mid-range rather than high.
Reversibility (2.2/5.0): Reversibility is mostly good but slower than the short peptides. Stop the drug and IGF-1 and growth hormone normalize within weeks, with no documented permanent harm, which is genuinely reassuring on safety. The mild negative is that the benefits reverse along with the risks, so the lean-mass gains wash out too. It is slower to clear than the roughly 30-minute peptides, since MK-677 has about a 24-hour half-life, but it is still a clean stop with no taper required.
Is MK-677 (Ibutamoren) worth it?
MK-677 sits at a Neutral 4.8 because it is the best-evidenced growth-hormone secretagogue you can name and still not a clear win, which is an unusual place to land. The practical read: if you want oral convenience, deeper sleep, and lean-mass support, and you genuinely accept a certain glucose cost plus a cardiac caveat, it is a reasonable monitored experiment on verified product. If you are chasing proven strength, function, or longevity, the data actively argues against it, and a cleaner path exists. The score is justified because a strong evidence base full of negative results is exactly that, strong and discouraging at the same time.
Merck developed MK-677 for years and never brought it to market. Despite evidence of target engagement, it was ineffective at slowing the progression of Alzheimer disease, the cleanest sign that raising IGF-1 is not the same as helping. Sevigny 2008
✅ Best for: Experienced users who value an oral, once-daily option over injections and will not miss the needle. People whose main goals are deeper sleep and lean-mass support rather than maximal strength, since the strength evidence is absent. Older adults with lower baseline growth hormone, who tend to respond more on the hormone markers. Anyone with clean fasting glucose and no cardiac history who will actually track glucose, HbA1c, and IGF-1 on a schedule. Users who can source third-party-tested material and verify identity, given documented mislabeling.
❌ Avoid if: You have diabetes, pre-diabetes, or metabolic syndrome, because MK-677 reliably worsens glucose control. You have heart failure or significant cardiac disease, given the congestive-heart-failure signal that halted a trial and the fluid-retaining mechanism. You have active or prior cancer, since IGF-1 is mitogenic and chronically raising it is a theoretical tumor-promotion risk. You compete in tested sport, since it is banned at all times under WADA category S2. You cannot verify source quality, because grey-market products are frequently mislabeled and sometimes contain other unapproved drugs entirely.
What is MK-677 (Ibutamoren) best for?
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
| Use Case | Score | Summary |
|---|---|---|
| ○ Body Composition / Fat Loss Primary | 4.2 | Body composition is MK-677's best-documented effect, which is why it scores highest, but the win comes with an asterisk. The 2-year Nass 2008 trial added about 1.1 kg of fat-free mass versus a small loss on placebo, the cleanest body-composition data in this class. The catch is that the same trial saw body weight rise 2.7 kg with no drop in visceral or total fat, and limb fat actually increased more on the drug. So it builds lean tissue and adds some weight and water at the same time, rather than leaning you out. The added mass also came with no strength or function gain, so this is body-composition movement on a scale and scan, not a proven performance benefit. |
| ○ Muscle Growth / Hypertrophy Primary | 3.6 | Muscle growth is supported by the lean-mass data but undercut by what that mass did, which is why it lands mid-range. The Nass 2008 trial confirmed about 1.1 kg of fat-free mass over a year, a real, replicated effect that beats the injectable peptides for human proof. But the authors stated plainly that the added fat-free mass did not produce any change in strength or function. Some of the gain is intracellular water rather than contractile tissue. So you can expect a fuller, slightly heavier look, but the evidence does not show it translates into the strength most people are chasing. |
| ○ Sleep Quality Primary | 4.0 | Sleep is one of MK-677's more consistent and pleasant effects, which earns it a high score. In young subjects, Copinschi 1997 showed roughly a 50 percent increase in deep stage-IV sleep and over a 20 percent rise in REM at the 25 mg dose, with older subjects gaining about 50 percent more REM. That maps onto the common community report of deeper, heavier sleep, often with vivid dreams. The trade-off is morning grogginess in the first week or two for some people, which usually fades. Pre-sleep dosing is the standard timing precisely because of this effect. |
| ○ Recovery / Repair Primary | 3.4 | Recovery rests on growth-hormone and IGF-1 physiology plus the nitrogen-balance data rather than a dedicated human recovery trial. Murphy 1998 showed MK-677 reversed diet-induced muscle breakdown, flipping nitrogen balance positive during caloric restriction, which is a real anti-catabolic signal. Better sleep also plausibly aids recovery. But no controlled trial has measured tendon healing, training recovery, or soft-tissue repair on MK-677 directly, and the hip-fracture recovery study was mixed and halted early. So the recovery case is mechanistically sound and partly evidenced, but not proven for the outcomes most people want. |
Frequently Asked Questions
What is MK-677, and how does it actually work?
MK-677, or ibutamoren, is an oral, once-daily growth-hormone secretagogue that activates the growth-hormone-secretagogue receptor, the same receptor the hormone ghrelin uses. It is not a SARM and not a peptide; it is a small molecule you swallow. By acting on that receptor, it amplifies your own pulsatile growth-hormone release and raises IGF-1, per Patchett 1995. Because it works through the ghrelin receptor, it also stimulates appetite. Its big convenience edge over ipamorelin and other injectables is the once-daily oral dose.
How much MK-677 do people take, and when?
Every published efficacy trial used 25 mg once daily, and grey-market practice commonly runs 10 to 25 mg once daily, often pre-sleep, per Chapman 1996. None of these are approved doses. Many people start near 10 to 12.5 mg to blunt the appetite surge and water retention before titrating up. Pre-sleep timing leans on the sleep data and the natural overnight growth-hormone pulse, while a few users dose in the morning to avoid grogginess. Cycling in 8 to 16 week blocks is a community habit, not a clinical rule.
What does the human evidence on MK-677 actually show?
MK-677 has the deepest human-evidence base in its class, including a 2-year trial and a 563-patient pivotal study, far more than the injectable peptides. The 2-year Nass 2008 trial added about 1.1 kg of fat-free mass and raised IGF-1 into the young-adult range. The honest catch is that the same trial found this lean mass produced no strength or function gain, and the disease trials failed. So the evidence is strong on biomarkers and body composition, weak on proven real-world outcomes.
Does MK-677 raise blood sugar or cause insulin resistance?
Yes, MK-677 consistently raises fasting glucose and lowers insulin sensitivity in every long study, which is a real harm rather than a quirk. Fasting glucose climbed from 5.4 to 6.8 mmol per liter at four weeks in Chapman 1996, and insulin sensitivity dropped over one to two years in Nass 2008. This is mechanistically expected, since growth hormone opposes insulin. The effect generally reverses once you stop, but anyone with pre-diabetes or metabolic syndrome should treat this as a strong reason to avoid it.
What is MK-677 bloat and water retention?
MK-677 bloat is the water retention and facial puffiness that many users notice in the first weeks, and it is a documented adverse event, not just an anecdote. The Nass 2008 trial listed transient mild lower-limb edema among the most frequent effects, alongside increased appetite. It comes from the growth-hormone axis holding onto sodium and water. Lowering the dose, dosing in the morning, or cycling usually eases it, and it reverses once you stop. Some people also report carpal-tunnel-type tingling from the same fluid effect.
Why did the MK-677 Alzheimer's and frailty trials fail?
The trials failed because raising IGF-1 did not translate into clinical benefit, which is the program's core lesson. The 563-patient Sevigny 2008 Alzheimer's trial found no cognitive or functional improvement despite IGF-1 rising about 73 percent. The 2-year Nass 2008 frailty trial grew lean mass but produced no strength or function gain. Merck developed it for years and never brought it to market. So target engagement was never the problem; converting that into outcomes was.
Is MK-677 safe, and what is the heart-failure concern?
MK-677 carries real safety drawbacks: certain metabolic harm, common edema, and one serious heart-failure signal. A hip-fracture trial in frail elderly patients was halted early for a congestive-heart-failure signal, with the authors calling its safety profile unfavorable, per Adunsky 2011. That signal hit a comorbid population, so it may not generalize to healthy users, but it stopped a Merck trial. Anyone with heart disease, diabetes, or active cancer should avoid it, since IGF-1 is mitogenic and the fluid load can stress a weak heart.
How does MK-677 compare to injectable growth-hormone peptides?
MK-677 beats the injectable peptides on evidence and convenience but loses on metabolic safety. It has real human trials and an oral once-daily dose, where ipamorelin and CJC-1295 no-DAC rely mostly on mechanism and anecdote. The trade-off is its certain glucose harm and the heart-failure signal. Tesamorelin is the cleaner choice where indicated, since it is FDA-approved with a better metabolic profile, per Falutz 2007. Pick MK-677 mainly for oral convenience, not for a safety or outcome edge.
How fast does MK-677 work, and how long do the effects last?
Growth hormone rises within hours of the first dose, but the visible effects build over weeks to months, and most of them fade once you stop. Peak growth hormone hit 55.9 micrograms per liter on day one in Murphy 1998, with IGF-1 plateauing over two to four weeks and body composition shifting over months. Off the drug, IGF-1 and growth hormone normalize within weeks and the lean-mass gains largely wash out. So it is a maintain-to-keep-it tool, slower to reverse than the short peptides but still fully reversible.
What could change MK-677 (Ibutamoren)'s score?
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
The fastest path up is human outcome data showing the lean mass finally translates into strength or function, and the fastest path down is harder confirmation of the glucose or cardiac harm. Because the current score is pinned by a strong-but-negative evidence base, a single clean positive functional trial would move Efficacy and the overall score together. A confirmed cardiovascular signal in healthy users, by contrast, would push Safety toward the floor and drop it into Caution or Skip. The dimensions most likely to move first are Efficacy, Safety, and Durability.
| Scenario | Dimension shifts | New Score |
|---|---|---|
| A controlled trial shows MK-677 lean mass produces real strength or function gains | Efficacy 3.4 to 4.3, Breadth 3.2 to 3.8 | 5.1 / 10 ⚖️ Neutral |
| Long-term data shows the glucose effect is manageable and reversible in healthy users | Safety 3.3 to 2.8, Opportunity 3.0 to 2.6 | 5.0 / 10 ⚖️ Neutral |
| A durable, drug-free benefit after a cycle is demonstrated | Durability 2.0 to 3.2, Reversibility 2.2 to 2.6 | 4.8 / 10 ⚖️ Neutral |
| A cardiovascular safety signal is confirmed in otherwise-healthy users | Safety 3.3 to 4.2, Side effects 3.3 to 3.7 | 4.4 / 10 ⚠️ Caution |
| Independent testing keeps finding mislabeled or contaminated product | Safety 3.3 to 3.7, Bioindividuality 3.2 to 2.7 | 4.6 / 10 ⚖️ Neutral |
| A new trial confirms long-term insulin resistance and progression to diabetes risk | Safety 3.3 to 4.0, Efficacy 3.4 to 3.0 | 4.4 / 10 ⚠️ Caution |
Key Evidence Sources
- Patchett 1995, PNAS: design of L-163,191 (MK-0677), an orally active growth-hormone secretagogue with EC50 of 1.3 nM.. 1995 paper describing the molecule and its oral GH-releasing activity
- Howard 1996, Science: cloned the growth-hormone-secretagogue receptor, the molecular target of this drug class.. 1996 receptor-cloning study establishing the GHS-R target
- Chapman 1996, J Clin Endocrinol Metab: 25 mg/day raised 24-hour GH about 97 percent and IGF-1 into the young-adult range in healthy elderly, with fasting glucose rising.. 1996 dose-response RCT in healthy elderly showing GH/IGF-1 rise and the glucose signal
- Copinschi 1997, Neuroendocrinology: MK-677 increased deep stage-IV and REM sleep by roughly 50 percent in young subjects.. 1997 sleep study supporting the deep-sleep and REM effect
- Murphy 1998, J Clin Endocrinol Metab: MK-677 reversed diet-induced negative nitrogen balance, with peak GH of 55.9 micrograms per liter on day one.. 1998 crossover trial showing the anti-catabolic effect during caloric restriction
- Svensson 1998, J Bone Miner Res: 25 mg/day for 8 weeks raised both bone formation and bone resorption markers in obese young men.. 1998 bone-remodeling study showing increased turnover without proven net gain
- Nass 2008, Ann Intern Med: 2-year RCT (n=65) where MK-677 added 1.1 kg fat-free mass but produced no strength or function gain, with rising glucose and falling insulin sensitivity.. The landmark 2-year frailty and body-composition trial; the central function-negative result
- Sevigny 2008, Neurology: the growth hormone secretagogue MK-677 had no clinical effect on Alzheimer disease progression in a 563-patient trial despite IGF-1 rising about 73 percent.. The large negative Alzheimer disease pivotal trial showing target engagement without clinical benefit
- Adunsky 2011, Arch Gerontol Geriatr: hip-fracture Phase IIb terminated early for a congestive-heart-failure safety signal, with an unfavorable safety profile.. The program-stopping heart-failure safety signal in frail elderly patients
- Van Wagoner 2017, JAMA: of 44 products sold online as SARMs, many were mislabeled and ibutamoren appeared as an undeclared ingredient.. 2017 grey-market adulteration analysis documenting mislabeling and undeclared MK-677
- Falutz 2007, N Engl J Med: tesamorelin, a growth hormone-releasing factor and FDA-approved analogue, reduced visceral fat by about 15 percent in patients with HIV-associated lipodystrophy.. Related compound class comparison for the cleaner-cousin framing; this growth hormone-releasing factor in HIV patients gives mechanistic context as a parent compound class peer
What does the evidence say about MK-677 (Ibutamoren)?
Evidence on this intervention is summarized across three complementary streams: contemporary clinical research, pre-RCT-era pharmacology and observational use, and the traditional medical systems that documented it first. Convergence across streams signals higher confidence; divergence is surfaced honestly.
Modern Clinical Research
Confidence: Medium
Citations: Chapman 1996, Nass 2008, Sevigny 2008, Adunsky 2011
Pre-RCT-Era Pharmacology and Use
Confidence: Limited
Citations: Patchett 1995
What to Track If You Try This
These are the data points that matter most while running a 30-day Experiment with this intervention.
How to read this section
- Pre
- Test or score before starting the protocol. Anchors a baseline.
- During
- Track while running the protocol so you can see if anything is changing.
- Post
- Re-test after a full cycle to confirm the change held.
- Up
- The marker should rise. For most positive outcomes, that is a good sign.
- Down
- The marker should fall. For most positive outcomes, that is a good sign.
- Stable
- The marker should hold steady. Big swings in either direction are a yellow flag.
- Watch
- Direction depends on dose, timing, and your baseline. Pay close attention to the trend.
- N/A
- No expected direction. The entry is there to anchor a baseline reading.
- Primary
- The Pulse dimension most likely to shift. Track this first.
- Secondary
- Also relevant, but a smaller or less consistent shift. Track if Primary is unclear.
Bloodwork to Order
Open These Markers In Your Dashboard
- IGF 1 Pre | Expected Watch During | Expected Up
- Fasting Glucose During | Expected Watch
- HbA1c During | Expected Watch
Pulse Dimensions to Watch
- Sleep During | Expected Up | Primary
- Body During | Expected Watch | Secondary
- Energy During | Expected Watch | Tertiary
Subjective Signals (Daily Voice Card)
- Edema or facial and limb puffiness Scale 1-5 | During | Expected Watch
- Appetite surge or unusual hunger Scale 1-5 | During | Expected Watch
Red Flags: Stop and Consult
- Rising fasting glucose or HbA1c: stop and consult a clinician, especially with diabetes or pre-diabetes.
- New edema or any breathlessness, ankle swelling, or unusual fatigue: stop, given the documented congestive-heart-failure signal.
- Any active or suspected cancer: do not use, because growth-hormone and IGF-1 signaling can promote proliferation.
- Carpal-tunnel-type numbness or tingling that worsens: reduce the dose or stop.
Other interventions for Body Composition
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. Tier bands: Skip 0–3.6, Caution 3.7–4.7, Neutral 4.8–5.7, Worth Trying 5.8–6.9, Strong Recommend 7.0–7.9, Top-tier 8.0+.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 2.275 − 2.499 = -0.224
Formula v0.5 maps EV = 0 to score 5.0. Above neutral, 1 EV point equals 1 score point. Below neutral, 1 EV point equals about 0.71 score points, so EV = −7 reaches 0.0 while EV = +5 reaches 10.0. Both sides use the full 5-point half-scale.
Score = 5 + (-0.224 / 7) × 5 = 4.8 / 10
