What Is Ibutamoren (MK-677)?
Ibutamoren (MK-677) is a growth hormone secretagogue and ghrelin receptor agonist.
It increases the endogenous secretion of GH and IGF-1.
A growth hormone secretagogue is simply a substance that signals the pituitary gland in your body to secrete more growth hormone.
MK-677 is orally bioavailable, therefore it can be swallowed (no injections needed).
To date, there have been no viable orally bioavailable alternatives to synthetic human growth hormone injections.
Much like SARMs, it is non-steroidal, but contrary to popular belief, MK-677 is not a SARM in any capacity, despite commonly being thrown into that category.
MK-677 will not negatively affect natural testosterone levels or endocrine function in any capacity at all, as it does not suppress any male sex hormones.
MK-677 has a much longer shelf-life than reconstituted GH, and does not need to be stored in the fridge or freezer to prevent degradation.
Clinical trials are currently assessing how viable of a potential treatment MK-677 is for addressing growth hormone deficiencies, muscle wasting diseases, Osteoporosis and a myriad of other related conditions.
MK-677 Effects
Increases Bone Density
In a 12 month study conducted on postmenopausal osteoporotic women, 25 mg of MK-677 per day increased bone mineral density and was well tolerated without any significantly concerning side effects.
In a 2 month randomized, double-blind, parallel, placebo-controlled study on 24 healthy obese men (ages 19-49), 25 mg of MK-677 per day increased markers of bone formation within the first 2 weeks, and increased serum osteocalcin levels at the 2 month mark.
Predictably, large increases in serum IGF-1 levels were also noted.
In a clinical study evaluating the changes in serum IGF‐I and markers of bone turnover in 187 elderly adults (65 years or older) lasting 2–9 weeks, dosages of 10-50 mg were administered once daily.
All treated individuals experienced increased bone turnover, regardless if they were healthy or functionally impaired men or women.
Builds Muscle
Growth hormone (GH) can accelerate lipolysis, and has an anabolic effect in muscle tissue by increasing insulin-like growth factor (IGF)-I and nitrogen retention.
In a 2 month study on 24 healthy obese men using 25 mg of MK-677 per day, 3 kg of lean muscle mass was gained in the MK-677 treated group compared to the placebo group.
According to a DEXA scan, total body fat did not change during the study, equating to a gain of 6.62 pounds of muscle in the MK-677 treated group.
It should be noted that this conclusion has limitations, due to the fact that intracellular water very likely contributed a fair portion of that “fat-free mass” that was gained.
In another study conducted on sixty-five healthy men and women ages 60-81, 25 mg MK-677 per day increased fat-free mass (FFM) by 1.6 kg relative to placebo.
The average lifetime loss of fat-free mass in adults is ~ 5.5, therefore MK-677 has exhibited the potential to offset aging induced catabolism by as much as 29%.
Increases BMR
Basal Metabolic Rate (BMR) was increased by MK-677 at 2 weeks of treatment, even after correction for the increase in fat-free mass.
Due to its positive effect on body composition, there is a case to make in regards to MK-677 being a possible treatment for obesity.
BMR (a) and BMR corrected for the increase in FFM (b) during 2-month treatment with MK-677 (25 mg) or placebo daily
Increases Nitrogen Retention
Ibutamoren exhibits blatantly anti-catabolic properties, one of which is its ability to retain nitrogen even in a steep caloric deficit.
Eight healthy volunteers (ages 24–39 yr) were calorically restricted (18 kcal/kg·day) for two 14-day periods.
During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily.
MK-677 reversed nitrogen wasting caused by the caloric deficit, suggesting that if these short-term anabolic effects are sustainable, it could be a viable treatment for those experiencing chronic disease, or other muscle wasting catabolic conditions.
Improves Sleep Quality
A study with eight young subjects (18-30 years) and six older subjects (65-71 years) found that MK-677 was able to increase REM sleep by as much as 50%.
Many anecdotal logs report much deeper sleep as a result of MK-677 usage as well (myself included).
Longevity
Natural Growth Hormone secretion downregulates with age, consequently lowering serum IGF-1 levels in the body, which results in significant lean muscle catabolism and increased mortality.
By restoring GH and IGF-1 levels to that of young healthy adults, it is likely that a significant amount of muscle and bone degradation could be prevented entirely.
In a study conducted on sixty-five healthy men and women ages 60-81, 25 mg MK-677 treatment per day resulted in increases in GH and IGF-1 levels to levels seen in young adults.
In another study conducted on one hundred sixty‐one hip‐fracture patients aged 65 and older, 25 mg MK-677 treatment per day increased serum IGF‐I levels by 84%.
Higher levels of IGF-1 are also associated with longer telomere length (a generally accepted marker of aging).
Improves Immune System
A study on mice showed that a growth hormone secretagogue could generally duplicate the same enhancement of the immune system observed by treating mice with synthetic GH injections.
Statistically significant changes in immunological parameters in the young and old mice treated with the growth hormone secretagogue were noted.
Tumor resistance increased substantially, and there were signs of anti-aging whereby a deficiency in the thymus in mice (a result of aging) was reversed entirely [R].
Currently, growth hormone injections are an approved treatment for treating muscle wasting caused by AIDS, and the findings in this study would suggest that a growth hormone secretagogue like MK-677 could fulfill a clinical need for AIDS patients and individuals undergoing chemotherapy and irradiation.
It would also have the obvious advantage of being orally bioavailable, whereas GH can only be administered via injection.
Hair Loss Prevention
IGF-1 has been shown to affect follicular proliferation and differentiation, remodelling of tissue, as well as the hair growth cycle itself.
More evidence is arising to suggest that IGF-1 plays an important role as a regulator in hair follicle biology.
It should be noted that patients with growth hormone (GH) deficiency resulting from defective hormone binding with low serum IGF-1 levels exhibit very sparse hair growth.
Anecdotally, several users of synthetic GH injections and Ibutamoren have reported a faster growth rate of their hair, as well as improved overall hair density.
Prevention Of Growth Hormone Deficiency
MK-677 has exhibited the ability to increase serum GH and IGF-1 levels to that of a young healthy adult, thus it was obviously desirable to assess if it could be a potential alternative treatment to growth hormone injections for those diagnosed with growth hormone deficiency.
In a study conducted on nine severely GH-deficient men ages 17-34 yr who had been treated for GH deficiency with GH during childhood, once daily dosages of 10 or 50 mg MK-677 or placebo were administered.
10 mg MK-677 increased serum IGF-1 levels by 52% on average, and increased GH levels by 79% on average.
50 mg MK-677 increased serum IGF-1 levels by 79% on average, and increased GH levels by 82% on average.
These improvements are indicative of Ibutamoren's potential as an alternative form of treatment for GH deficiency during childhood.
Benefits Of Higher GH Levels and IGF-1 Levels
Healthy GH and IGF-1 levels support a variety of positive benefits in the body.
As mentioned earlier, these benefits include anti-aging properties, which is why HGH is commonly referred to as the real “fountain of youth.”
GH Benefits
GH promotes and increases the synthesis of new protein tissues, allowing new muscle to be built
Metabolizes fat incredibly well, improves complexion,
Has dramatic anti-aging properties
Increases hair growth (where you want it)
Improves sleeping patterns (making for fewer unintended awakenings and better REM-stage sleep)
Produces more energy
May improve sexual performance
Increases bone density which prevents injury and helps promote healing
Can improve the quality and duration of heart and kidneys
IGF-1 Benefits
IGF-1 supports cellular division (hyperplasia), making it the only hormone that can actually create brand new muscle cells via muscular cell division.
Supports the repair of nerve damage
Lowers body fat levels
Exhibits anti-aging properties by tightening up loose skin
Aids in the repair of bones, tendons and ligaments.
IGF-1 Hyperplasia
The cellular division aspect of IGF-1 is what makes it so attractive to bodybuilders and athletes, as an individuals “genetic potential” essentially refers to how much hypertrophy can be induced in a person's muscle cells.
Only so much hypertrophy can be achieved, even with the addition of exogenous anabolic steroids and/or insulin.
The two primary mechanisms by which muscle mass may be increased are hypertrophy (increase in myofibre size), and hyperplasia (increase in myofibre number).
It is generally well accepted that there are a fixed amount of fibres within a muscle, however, it has been suggested that cell splitting can occur in these fibres [R].
While there is no evidence of this in humans via clinical studies, bodybuilders hypothesize that supraphysiological amounts of IGF-1 in the body can cause cellular hyperplasia, whereby myofibres split in two, to create brand new muscle fibres.
In theory, via this process, one could split new muscle cells, and then induce hypertrophy in those new muscle fibres and achieve greater levels of musculature than would have been possible otherwise via resistance training, diet and hormonal assistance.
MK-677 Dosage
MK-677 exhibits a dose dependent positive effect on serum GH and IGF-1 levels.
The clinical data suggests that Ibutamoren begins exhibiting diminishing returns above and beyond dosages of 25 mg per day.
The remains consistent among the majority of the clinical studies, with almost every trial utilizing a once daily oral dosage of 25 mg of MK-677 to assess Ibutamoren's efficacy relative to placebo.
When comparing high dosages of MK-677 to low dosages, there wasn't a significant difference between GH levels at dosages of 10 mg and 50 mg per day, however, there was a significant difference in serum IGF-1 levels between the 10 mg per day dosing group, and the 50 mg per day dosing group.
In severely GH-deficient men ages 17-34 yr, on average, 10 mg MK-677 increased serum IGF-1 levels by 52%, and increased GH levels by 79%, while 50 mg MK-677 increased serum IGF-1 levels by 79%, and increased GH levels by 82%.
Side Effects
Increased Appetite
MK-677 will almost undoubtedly greatly increase appetite.
Besides acting as a potent growth hormone secretagogue, MK-677 is also an oral ghrelin mimetic.
Ghrelin is the “hunger hormone” that your stomach secretes in order to regulate your appetite.
By artificially stimulating the secretion of that hormone, the body is tricked into being hungry, even when it wouldn't have been otherwise.
MK-677 has a very significant effect on the ghrelin receptor, more so than any other ghrelin receptor agonist with the exception of GHRP-6.
How MK-677 and GHRP-6 differ is that GHRP-6 is in and out of the body very quickly (half-life of 20 minutes), whereas MK-677 will simulate the actions of ghrelin for several hours, thereby resulting in greatly increased levels of hunger all day long.
While MK-677 has a positive effect on body composition, I don't believe the clinical data takes into account how important diet adherence really is when it comes down to what will get someone in shape.
In almost all cases, having chronic ghrelin receptor stimulation would make it nearly impossible to stick to a strict caloric deficit in order to reap the true metabolic benefits that Ibutamoren can provide in the first place.
It's easy to see why this compound is recreationally used so often as an appetite stimulant, as the ghrelin mimetic properties are incredibly potent.
Lethargy
Though not reported in the clinical data, I can assure you that anything that increases your GH and IGF-1 levels will increase your lethargy.
Regardless if GH/IGF-1 is increased via synthetic gh injections, growth hormone releasing peptides, or growth hormone secretagogues like MK-677, increased levels of lethargy is an expected and common side effect.
Intense Dreams
Dreams (both lucid and non-lucid) are much more common during the REM cycle of sleep.
As sleep affects the regulation of growth hormone (GH), typically, getting a deep and restful sleep is associated with optimal growth hormone secretion, and consequently, more dreaming.
Stimulation of endogenous GH secretion with MK-677 can improve sleep quality, promote the body to enter the REM cycle, and in turn experience more dreams.
Water Retention
A common side effect from elevated GH and IGF-1 levels is water retention.
Expectedly, the most common side effect aside from increased appetite was transient edema and muscle pain in clinical trials.
The muscle pain likely being an indirect side effect caused by intracellular water retention putting increased stress on the joints and muscles.
Increased Blood Pressure
Increased blood pressure is an indirect side effect resulting from edema, which is one of the most common MK-677 side effects.
Elevated Blood Sugar & Reduced Insulin Sensitivity
Although several clinical studies found no change in blood glucose levels, there were a couple studies where MK-677 caused an elevation of fasted blood glucose levels and decreased insulin sensitivity.
GH causes blood sugar levels to rise, which in turn requires the pancreas to work harder to compensate and release insulin to bring blood sugar levels back down to homeostasis.
Chronic GH elevation can create chronic pancreatic stress in certain scenarios, which eventually can result in pancreatic beta cell degeneration, and insulin resistance.
Chronic blood glucose elevation and pancreatic cell degeneration is what eventually leads to Type 2 Diabetes.
Individuals with other lifestyle factors that contribute to insulin resistance as is (excessive carbohydrate intake, holding too much body fat, lack of exercise, etc.), or have genetic predispositions that increase their likelihood of Diabetes, could potentially end up pushing themselves over the brink and become Type 2 Diabetic with MK-677 or synthetic growth hormone usage.
Reactive Hypoglycemia
MK-677 can raise blood glucose levels, which is a mechanism that is autocorrected and regulated by the pancreas in healthy individuals.
In insulin resistant individuals, MK-677 can cause reactive hypoglycemia, whereby sharp spikes in blood sugar can cause an exaggerated level of insulin secretion and glucose uptake into the cells, consequently crashing blood sugar and causing hypoglycemia.
This poor endogenous regulation of blood glucose levels is typically indicative of some degree of insulin resistance in an individual.
Signs and symptoms of reactive hypoglycemia may include hunger, weakness, shakiness, sleepiness, sweating, lightheadedness and anxiety.
Potential Cancer Cell Hyperplasia
Despite the clinical data showing a positive effect on resistance to tumor progression and upregulation of the immune system in mice, the proliferative properties of IGF-1 inherently suggest that MK-677 could potentially accelerate the growth rate of existing cancer cells in the body.
This is why Metformin is shown to help prevent cancer, because it lowers serum IGF-1 levels in the body.
This is also an argument commonly made as to why high levels of IGF-1 will shorten the lifespan of a person, rather than extend it.
Tingly Or Numb Fingers And Hands
This is a common side effect of elevated growth hormone levels, and is commonplace among anecdotal reports on Ibutamoren.
Enhanced Fear In Rats
One study on rats evaluated MK-677's potential to cause enhanced levels of fear.
There is evidence to support that one of the ways ghrelin is modulated is through exposure to stress.
What this study intended to assess specifically was if rats would have a greater likelihood of experiencing fear and posttraumatic stress disorder (PTSD) when their ghrelin receptors are artificially stimulated 24/7 with a ghrelin receptor agonist (MK-677).
So, rats were continuously administered MK-677, and frightened constantly, and their difference in response (MK-677 treated vs non treated) was assessed.
Rats with chronic ghrelin elevation were found to have enhanced fear memory compared to baseline.
This same response has yet to be replicated in human trials, or in anecdotal logs.
PCT (Post Cycle Therapy)
MK-677 does not cause endocrine suppression, it doesn't lower natural testosterone levels, and it doesn't inhibit LH, FSH or SHBG.
It does not raise estrogen either, which has an indirect effect on testosterone suppression.
As MK-677 doesn't suppress any sex hormones, or increase any antagonizing hormones, there is no hormonal suppression that occurs via MK-677 use, and therefore would not require a PCT phase.
Half-Life
The elimination half-life of MK-677 is 4.7 hours; with IGF-1 levels remaining elevated with a single oral dose for up to 24 hours.
Once per day dosing of MK-677 has proven to be a viable frequency of administration throughout all of the clinical studies to date.
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