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MK-677 Ibutamoren Chemical Structure And Mechanism Of Action

MK-677 (Ibutamoren) – Results, Clinical Trials & Reviews



Ibutamoren (developmental code name MK-677) is an orally-active growth hormone secretagogue and ghrelin receptor agonist being researched as a potential treatment for growth hormone deficiency and sarcopenia [R, R, R, R, R].

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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) [R].

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 [R].

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 [R].

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 [R].

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 [R].

Builds Muscle

Growth hormone (GH) can accelerate lipolysis, and has an an anabolic effect in muscle tissue by increasing insulin-like growth factor (IGF)-I and nitrogen retention [R].

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 [R].

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% [R].

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 [R].

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
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 [R].

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% [R].

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 [R, R].

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 [R].

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% [R].

Higher levels of IGF-1 are also associated with longer telomere length (a generally accepted marker of aging) [R].

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 [R].

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 [R].

Mechanism Of Action

Growth hormone is secreted by the somatotrophes of the anterior pituitary gland in multiple pulses each day.

Growth hormone is released into the blood stream and then stimulates the liver to produce insulin-like growth factor-1 (IGF-1), which stimulates linear growth before epiphyseal fusion and also exerts several metabolic effects throughout life.

After ingestion, MK-677 increases somatotrophe secretion of GH via signalling the pituitary gland to secrete a sufficient amount of growth hormone [R, R].

The most common cause of GH deficiency in childhood is believed to be caused by a lack of adequate stimulation of the pituitary gland by hypothalamic GHRH, which is why something like Ibutamoren which can systemically increase IGF-1 levels for 24 hours with a single oral dose is very promising for potential clinical use [R].

The likely mechanism of action following MK-677 administration is the activation of the ghrelin receptor by MK-677, with feedback by IGF-I preventing excess GH production [R].

The mechanism of action through which MK-677 promotes GH secretion is comparable to growth hormone releasing peptides like GHRP-6, GHRP-2, Ipamorelin and Hexarelin, with GHRP-6 being the most similar in regards to the amount of ghrelin receptor activation that occurs post-administration.

MK-677 does not stimulate a greater quantity of secretion events per day (number of GH pulsations), but rather it stimulates a greater total 24 hour GH production rate [R].

In other words, Ibutamoren can substantially increase the strength of each GH pulsation that occurs in the body.

EFFECTS OF TREATMENT ON 24-H MEAN GH AND IGF-I AND GH SECRETORY DYNAMICS
Effects of treatment on 24-hour mean GH and IGF-1 and GH secretory dynamics

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 Clinical Trials

Lumos Pharma acquired the license for Ibutamoren (MK-677) in September, 2018 [R].

The compound was thereafter referred to as “LUM-201” by the company.

LUM-201 Pipeline
LUM-201 Pipeline

Right now, MK-677 (LUM-201) is in phase 2 trials being investigated as a potential treatment for Pediatric Growth Hormone Deficiency (PGHD).

To date, MK-677 has been studied in more than 1200 people (~200 children and~1000 adult and elderly patients), and was generally well tolerated.

MK-677 Limitations

While MK-677 will effectively stimulate the secretion of growth hormone in those with a functioning hypothalamic pituitary adrenal (HPA) axis in most cases, there are certain scenarios in which it is ineffective.

  1. Individuals who have a non-functioning hypothalamic pituitary adrenal (HPA) axis
  2. Individuals who are unable to secrete growth hormone
  3. Individuals who simply do not respond to MK-677 at all
  4. Approximately 30% of children with PGHD will not be able to restore healthy GH and IGF-1 levels with MK-677 treatment

MK-677 Results (Anecdotal/Recreational Use)

There are several testimonials online reviewing Ibutamoren's applications in a performance enhancing context.

These logs are anecdotal, but anecdotal experiences still can provide insight into how MK-677 performs in scenarios that will very likely never be assessed in clinical studies.

In certain cases, anecdotal logs can actually be far more revealing of important information than clinical studies.

A good example of that is the selective androgen receptor modulator (SARM) Andarine and its potential to cause temporary vision impairment, which is a side effect that was not discovered during its development (although perhaps it could be the reason why it was abandoned).

Anecdotal experiences of Ibutamoren commonly compare its effects to synthetic GH injections.

It is becoming more common for athletes seeking performance enhancement to turn to MK-677 before GH due to the prohibitive costs of HGH, the convenience of oral administration over injections, more flexible storage requirements, and nearly identical results when comparing Ibutamoren to modest dosages of daily GH injections.

Gains of 5-10 pounds of fat-free mass within the first few weeks of MK-677 use are commonly reported, however, it should be noted that the majority of that is intracellular water.

My MK-677 Review

I have used MK-677 a few times over the past couple years now.

Each time the results have been fairly dramatic, even while on moderate dosages of anabolic steroids.

In my experience, intramuscular water and nitrogen retention is more apparent with MK-677 than GH.

That can be a good and bad thing though, depending on the goals of the user.

Every time I have used MK-677, within a week my weight would jump up 7-10 pounds.

The only thing that I can think of that will make more of a dramatic difference in that short a span of time is Dianabol.

This isn't necessarily a positive thing though, and can actually be seen as a negative, depending on the goals of the user as I mentioned above.

If I had to compare 25 mg of MK-677 to something I would compare the results to 2 iu’s of high quality generic GH, or a few daily 100 mcg injections of GHRP-6 coupled with concurrent 100 mcg injections of Modified GRF (1-29).

The short-term cosmetic changes and appetite increase caused by MK-677 are much more comparable to multiple injections of GHRP-6 + Modified GRF (1-29) than traditional GH though.

When I use MK-677 I experience ravenous hunger that makes it nearly impossible to adhere to a reasonable caloric intake.

This is due to MK-677's interaction with the ghrelin receptor.

The incredibly heightened appetite is the main reason I avoid this compound now, as I cannot cut down to sub 10% body fat when I have above average levels of ghrelin receptor activation around the clock.

Its appetite stimulating effects seem to subside to a large extent after a few weeks of continuous use, which makes it more tolerable, but I now avoid using ghrelin mimetics entirely unless I am eating above maintenance.

I've also noticed that MK-677 seems to very significantly offset hair loss.

Every time I use MK-677, my hair grows much faster, and there is a remarkable improvement in my hairs overall density.

Areas that are normally more diffuse than I prefer fill in quite a bit, very quickly whenever I use MK-677.

It has become my candidate of choice among growth stimulators for hair loss prevention.

In terms of side effects, I have noticed some fairly significant lethargy from MK-677 (anything that raises GH and IGF-1 will do this), however, I was able to mitigate that to some extent by taking my daily dosage right before going to bed.

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% [R].

How Much Does MK-677 Increase GH And IGF-1 Levels?

MK-677 has exhibited substantial increases in serum GH and IGF-1 levels in multiple clinical trials now.

In a 12 month study conducted on postmenopausal osteoporotic women, 25 mg of MK-677 per day administered with or without alendronate for 12 months increased IGF-1 levels by approximately 40%.

Serum IGF-1 levels appeared to start tapering down over the next 11 months after they peaked in month 1. This suggests that utilizing MK-677 in a cyclical fashion may be a more beneficial way of maximizing its efficacy during use [R].

In the 2 month study on 24 healthy obese males , after two weeks of treatment with 25 mg of MK-677 per day serum IGF‐I levels increased approximately 40% compared with pretreatment values and this effect was sustained throughout the treatment period [R, R].

Serum concentrations of IGF-1 and IGFBP-3 during 2-month treatment with MK-677 (25 mg) or placebo daily in obese males
Serum concentrations of IGF-1 and IGFBP-3 during 2-month treatment with MK-677 (25 mg) or placebo daily in obese males

In a 2 year study including sixty-five healthy men and women ages 60-81, daily MK-677 significantly increased GH and IGF-1 levels to those of healthy young adults without serious adverse effects [R].

Serum 24-h mean GH results in pivotal year 1
Serum 24-h mean GH results in pivotal year 1
Serum 24-h mean IGF-1 results in pivotal year 1
Serum 24-h mean IGF-1 results in pivotal year 1

In a study conducted on nine severely GH-deficient men ages 17-34 yr, 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 [R].

Placebo Vs 10mg MK-677 Vs 50mg MK-677 in GH deficient men - GH Levels
Placebo Vs 10 mg MK-677 Vs 50 mg MK-677 in GH deficient men – GH Levels
Placebo Vs 10mg MK-677 Vs 50mg MK-677 in GH deficient men - IGF-1 Levels
Placebo Vs 10 mg MK-677 Vs 50 mg MK-677 in GH deficient men – IGF-1 Levels

MK-677 Bulking Cycle

In a calorie surplus MK-677 will promote more lean muscle gains than would otherwise be possible to gain naturally.

For use in a performance enhancing context, cycles like the following are commonplace among users.

SARMs like LGD-4033, Ostarine, RAD140 or S4 are commonly stacked alongside MK-677 in more involving performance enhancement bulking protocols.

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 [R].

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 [R].

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 [R].

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 [R].

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 [R, R].

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 [R].

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 [R].

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 [R, R].

It does not raise estrogen either, which has an indirect effect on testosterone suppression [R].

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 [R].

Once per day dosing of MK-677 has proven to be a viable frequency of administration throughout all of the clinical studies to date.

MK-677 Vs HGH Injections

The majority of competitive bodybuilders and other performance enhancement seeking athletes view growth hormone as a valuable tool for enhancing their muscle growth and fat loss potential.

However, legitimate GH is simply unaffordable to most.

With a pharmacy-grade kit of GH being upwards of $600-1000 in many instances, it can be extremely cost prohibitive just to use a modest dosage on a daily basis.

With MK-677 exhibiting effects formidable to that of a modest dosage of pure GH in clinical trials, it is easy to see why it has garnered so much attention from those seeking performance enhancement.

MK-677 also has the advantage of being stable in room temperature, orally bioavailable, sustaining elevated IGF-1 levels 24 hours post-ingestion, and works via stimulating natural endogenous GH secretion, as opposed to exogenous synthetic GH injections which will increase serum GH levels irrespective of the body's current endogenous production without a feedback loop to regulate that hormone levels stay within healthy limits.

MK-677 Vs Peptides

The main drawback of growth hormone releasing peptides (GHRP's) is that they all require 3-6 injections per day to sustain stable blood serum concentrations because of their short half-lives.

MK-677 does not have this same issue, as once per day dosing elevates IGF-1 levels for up to 24 hours [R].

Although fast acting GH peptides can be effective, they are certainly not convenient at all, and just the nuisance of their required dosage frequency alone would likely drive away most people from considering it a viable GH alternative.

Another major disadvantage of GHRP's is their inhibited effects in the presence of glucose.

GHRP injections need to be timed correctly as elevated blood glucose levels render them dramatically less effective.

When the dosage frequency of a GHRP requires 3+ injections per day to achieve stable blood serum concentrations of GH and IGF-1, ensuring that blood glucose levels aren't elevated at the time of injection during each of these shots is extremely difficult, if not nearly impossible for individuals who aren't sitting at home doing nothing day in and day out.

Peptides also have the same limitations as GH, where they must be reconstituted, injected, and stored in a fridge to avoid degradation.

While comparing the pros and cons of MK-677 to peptides, the clinical data is generally in favor of MK-677.

However, it should be noted that there are a couple very effective combinations of the two where IGF-1 levels equivalent to high dosages of pharmaceutical grade GH can be achieved.

Supplements To Take With MK-677 (Optional)

Huperzine A

Certainly not mandatory, but if you want to maximize the benefits you can get from MK-677 it may be worthwhile to look at Somatostatin inhibitors.

A popular supplement that is commonly used with MK-677 is Huperzine A dosed at 200 mcg three times per day.

There are a couple studies with data that are often extrapolated to suggest that Huperzine A is a potent Somatostatin inhibitor [R, R].

When your body has higher than normal HGH levels, it will release Somatostatin as a counter measure to inhibit the secretion of growth hormone from somatotrope cells to bring HGH levels back to normal.

This mechanism is very similar to how the body uses Myostatin to inhibit excessive muscle growth.

In theory, Huperzine A would prevent Somatostatin from inhibiting pituitary released GH, and by using Huperzine A to inhibit Somatostatin, your body would then have more active/usable HGH.

This is all hypothetical, and the evidence to support the efficacy of Huperzine A in this process is weak.

However, Huperzine A is still a great Nootropic supplement, and it is very cheap.

I use it daily anyways, and if it inhibits Somatostatin then I just see it as a fringe benefit.

The reality is that the likelihood of it having a significant impact on the process of endogenous GH inhibition is low.

Insulin Mimetics

As MK-677 can increase your blood glucose levels via increased endogenous HGH production, using supplements as a countermeasure to keep your blood sugar lower and more stable may be a wise decision.

Insulin is what is responsible for shuttling nutrients to the muscle for recovery, and it has a direct and major impact on how both your muscle and fat cells utilize amino acids and glucose.

When your insulin sensitivity is high, muscle cells will readily absorb glucose and amino acids when insulin signals them to open.

However, when your insulin sensitivity is low as a result of having a high level of body fat accrued on your physique, eating too many high glycemic carbohydrates (or too many carbs in general), among other potential risk factors, your natural levels of insulin are so much higher that it can have a severe desensitizing effect on muscle cells and insulin’s nutrient shuttling effects.

Compounding the issue, with diminished insulin sensitivity your body will become more and more prone to convert more of the excess calories you intake as body fat, as the muscle cells are no longer absorbing and utilizing the consumed glucose and amino acids efficiently.

Berberine

Berberine is arguably the best over the counter supplement to improve insulin sensitivity.

Clinical research has shown that Berberine greatly promotes glucose absorption by muscle cells, and is so effective at reducing blood glucose levels it is comparable to Metformin (a prescription drug for blood sugar control).

*One important thing to note about Berberine is that it inhibits the enzyme CYP3A4, a member of the Cytochrome P450 family. This enzyme directly dictates how fast the liver can break down medications. Because of this, Berberine may slow down the rate at which the liver breaks down medications, equating to potentially longer life spans of medications you are using, as well as potentially inducing stronger overall effects from those medications than intended. One example in particular is if you are on TRT and use an Aromatase Inhibitor (AI) to keep your Estrogen levels in the sweet spot, having Berberine in your system may potentiate the effects of that AI (as the liver isn't breaking it down as efficiently as normal), which could potentially tank your Estrogen far below what it would normally be at on that same AI dosage without Berberine in your system. Keep this in mind prior to the usage of Berberine.*

Some other effective supplements at controlling blood sugar are

Cinnamon Extract

Cinnamon Extract has potent anti-diabetic effects, proving to aid insulin function by a significant degree (more than 20-fold in vitro), reducing blood glucose levels, and even improving blood lipid profile.

Other studies also noted blatant improvements in overall insulin sensitivity.

Alpha Lipoic Acid

A decrease in blood glucose is noted with oral supplementation of Alpha Lipoic Acid, encouraging heightened insulin sensitivity and nutrient partitioning.

Fenugreek

Clinical research has shown that Fenugreek lowers blood glucose levels and improves the body’s tolerance to glucose itself.

Fenugreek has even been used to mitigate blood sugar metabolism problems like Diabetes.

Kaempferol

Kaempferol encourages glucose uptake into myocytes and has been alleged to be as potent as insulin itself in regards to this process in particular.

It may also inhibit the enzyme responsible for the production of fatty acids deriving from glucose, meaning more fat loss (or less fat gain depending on the scenario).

Myricetin

Proven to improve blood glucose uptake, Myricetin decreases blood glucose levels and can actually aid in the reversal of the negative effects caused by metabolic syndrome.

The mechanism of action behind Myricetin’s benefits are similar to that of Kaempferol, and it also inhibits the uptake of glucose into fat cells, equating to less fat storage.

Irvingia Gabonensis

Irvingia Gabonensis reduces blood glucose levels and reduces fat storage through several anti-obesity mechanisms such as the inhibition triglyceride uptake.

Fucoxanthin

One study found a huge increase in metabolic rate with the supplementation of Fucoxanthin, roughly equating to an increased metabolic rate of around 450 calories per day.

This was one study though and requires replication to see if those astounding results can be achieved with other sample groups as well.

Regardless, it seems like a very promising compound, and it also was shown in studies to result in a significant decrease in blood glucose, and a significant increase in the uptake of glucose into skeletal muscle.

Chromium

Chromium is an essential mineral that regulates blood glucose, insulin metabolism, and can encourage insulin sensitivity in the body.

Appetite Suppressant

If you are dead set on cutting with MK-677 to get shredded, I highly suggest you get an appetite suppressant, as MK-677 will almost certainly increase your appetite significantly.

To be honest, I advise against cutting on MK-677 entirely unless you have adapted to the ghrelin receptor related appetite stimulation.

If you are just starting MK-677, I can almost guarantee you that you will not be able to adhere to a strict diet and calorie deficit with the intense hunger that MK-677 induces when you first start using it.

GH Gut

MK-677 will not directly cause “GH gut.”

However, it can contribute to it.

GH gut is something that is commonly attributed to the abuse of human growth hormone, however, MK-677 does not increase serum GH and IGF-1 levels in the body as high as supraphysiological dosages of growth hormone.

While it will increase blood sugar, it has not shown to be independently capable of causing GH gut without compounding factors like suboptimal body composition, poor diet and exogenous GH injections.

There is no documented case of this, I'm just asserting a hypothetical perfect storm scenario in which high levels of insulin resistance and compromised gut health could occur that would lead to “GH gut.”

Buy MK-677

Most MK-677 sources do not third party test their products, nor do they have any satisfactory level of quality control whatsoever.

I strongly advise that before you buy SARMs or MK-677 from a company online you thoroughly evaluate their track record, their third party test results, and how they are marketing their products in general.

These Are My Current Trusted/Go To Companies For Third Party Tested 99%+ Pure MK-677:

Disclaimer: The information included in this article is intended for entertainment and informational purposes only. It is not intended nor implied to be a substitute for professional medical advice. Prior to buying anything, check that it is compliant where you live with your current government laws.

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After dedicating over 8 years to extreme self-improvement, I have created "More Plates More Dates" as a one stop shop for helping you to get yourself on the right path to the "best you" possible too.

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