Low Dose MK 677 for Healthspan Extension

[BigTex]

Acromegaly is a disorder that occurs when your body makes too much growth hormone. IGF-1 levels are usually 2x normal levels for a long periods of time.

IGF is measured in nanograms per milliliter (ng/mL). The normal ranges are:

• 182-780 ng/mL for people ages 16-24
• 114-492 ng/mL for people ages 25-39
• 90-360 ng/mL for people ages 40-54
• 71-290 ng/mL for people 55 and up

As you can see from the norms, 2x the high ends are pretty damn high. In a 5 day study using MK 677, following the initial 7-day caloric restriction, insulin-like growth factor-I (IGF-I) declined from 232 ± 25 to 186 ± 19 ng/mL in the MK-677 group and from 236 ± 19 to 174 ± 23 ng/mL in the placebo group. Mean IGF-I concentration increased significantly during MK-677 to 264 ± 31 ng/mL (mean for the last 5 days of treatment) compared with 188 ± 19 ng/mL with placebo (P < 0.01).

Anyway you look at it, IGF-1 levels only rose from a baseline of ~232 to 264 for the 5 days treatment. MK 677 increases GH levels and IFG-1 levels but nothing near to what you see with acromegaly.

MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism1

The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, random

academic.oup.com

I know so many bodybuiders who regularly use 10-20iu of hGH daily and I have never seen one case of Acromegaly or cancer. I personally have used hGH since the early 80's and no issues. Mixed hGH and MK and no cancer. @BadassBlues is discussing using 10mg, far from the dose of 25mg used in most research.

Colao et al. reported that death in patients with acromegaly mainly occurs secondary to the presence of cardiovascular complications.

Systemic complications of acromegaly: epidemiology, pathogenesis, and management - PubMed

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular...

pubmed.ncbi.nlm.nih.gov

Here is another fun fact:

Each compound, GHRP6 and MK677 are both Growth Hormone Secretagogues.

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.

 

[BigTex]

The purpose of this thread is to investigate and discuss the potential of using MK 677 for anti-aging / health extension purposes. All points of view are welcome as long as it is relevant to the topic. Healthy debate is a good thing, I welcome all relevant input.

I have personally never used MK 677 and my interest in it is based off of the research I am currently doing. I personally have not seen anything from a safety aspect that would dissuade me from trying this to formulate my own opinion.

As stated above, from what I gather, the main complaint has been about side effects. I believe that is a highly variable aspect based on dosage, length of use and personal chemistry. Someone looking for the anabolic benefits rather than the anti aging possibilities would opt for the higher dosage and longer cycle. Hypertension was mentioned above and that is a possibility at higher doses due to water retention.

As to the subject of cancer, that one is the great unknown with regard to anything. We are all susceptible to that risk from virtually everything around us. I have seen no direct correlation with MK 677 usage and cancer. If someone could provide that as a study, rather than a hypothetical theory, I would be open to consider it. To say that there is no risk is not something anyone can calculate with absolute accuracy. I would however say that I personally see that risk as being very small and am comfortable with the odds. That is my personal opinion only. I respect anyone's right to have an opposing point of view.

I am not advocating that people start using MK 677 for the purposes discussed here, I am postulating the possible benefits of doing so. Any documented evidence contrary to using MK 677 is also welcome as we need to look at all sides in order to make an intelligent decision.

I agree, instead we got off quickly to bashing MK677 as a "poison." Yea, I saw this same concept pushed by the Australian government.

Now here is a paper that investigates the difference between 50mg and 10mg.

Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults - PubMed

To determine the effect of the GH releasing peptide (GHRP)-mimetic, MK-677, on the GH/insulin-like growth factor-I (IGF-I) axis in selected GH-deficient adults, we studied nine severely GH-deficient men [peak serum GH concentration in response to insulin-induced hypoglycemia of 1.2 +/- 1.5...

pubmed.ncbi.nlm.nih.gov

To sum it up, 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. What we can conclude from this is that 50 mg doesn’t result in much higher GH concentrations than 10 mg does, but it did result in significantly higher IGF-1 concentrations. So what is the difference? In general, high GH levels typically equate to more fat loss, anti-aging and healing, while high IGF-1 levels equate to more muscle growth. So if you are after the fat loss and the anti-aging/healing benefits of HGH the 10mg dose of MK-677 is the best.

Here is a study done on mice, showing that a growth hormone secretagogue (MK677 is a GH secretagogue) could generally duplicate the same enhancement of the immune system observed by treating mice with synthetic GH injections. 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. Will it work the same in humans?

Immune enhancing effect of a growth hormone secretagogue - PubMed

Growth hormone (GH) has been known to enhance immune responses, whether directly or through the insulin like growth factor-1, induced by GH. Recently a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the production of GH by the pituitary gland. In this study, we...

pubmed.ncbi.nlm.nih.gov

 

[BigTex]

I just found something interesting on ProMuscle. A guy did blood testing on MK67 before and after. He was on for 25 days when he tested and was using 50mg of MK677. He also was using 600mg of testosterone enanthate/wk

His total testosterone levels here high at - 2509.9 We know at levels like that total GH and IGF-1 could possibly increase. But here is the before (L) and after (R) on GH/IGF-1

Before - GH - 3.0ng/ml After - 2.3ng/ml (0.00-10.0ng/ml)
Before - IGF-1 - 232ng/ml After - 312ng/ml (98-282ng/ml)

So we know from previous research that higher and lower doses increase GH about the same, however larger doses increase IGF-1 more. MK-677 at a high dose on this blood work didn't increase GH. But it did increase IGF-1 but not nears the levels we see in cases of Acromegaly. This was a 30 year old man.

 

[BadassBlues]

Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects - PubMed

Aging is associated with declining activity of the GH axis, possibly contributing to adverse body composition changes and increased incidence of cardiovascular disease. The stimulatory effects on the GH-insulin-like growth factor I (IGF-I) axis of orally administered MK-677, a GH-releasing...

pubmed.ncbi.nlm.nih.gov

Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects​

I M Chapman 1, M A Bach, E Van Cauter, M Farmer, D Krupa, A M Taylor, L M Schilling, K Y Cole, E H Skiles, S S Pezzoli, M L Hartman, J D Veldhuis, G J Gormley, M O Thorner
Affiliations expand

• PMID: 8954023
• DOI: 10.1210/jcem.81.12.8954023

Abstract​

Aging is associated with declining activity of the GH axis, possibly contributing to adverse body composition changes and increased incidence of cardiovascular disease. The stimulatory effects on the GH-insulin-like growth factor I (IGF-I) axis of orally administered MK-677, a GH-releasing peptide mimetic, were investigated. Thirty-two healthy subjects (15 women and 17 men, aged 64-81 yr) were enrolled in a randomized, double blind, placebo-controlled trial. They received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. At baseline and on day 14 of each study period, blood was collected every 20 min for 24 h to measure GH, PRL, and cortisol. Attributes of pulsatile GH release were assessed by 3 independent algorithms. MK-677 administration for 2 weeks increased GH concentrations in a dose-dependent manner, with 25 mg/day increasing mean 24-h GH concentration 97 +/- 23% (mean +/- SE; P < 0.05 vs. baseline). This increase was due to an enhancement of preexisting pulsatile GH secretion. GH pulse height and interpulse nadir concentrations increased significantly without significant changes in the number of pulses. With 25 mg/day MK-677 treatment, mean serum IGF-I concentrations increased into the normal range for young adults (141 +/- 21 microgram/L at baseline, 219 +/- 21 micrograms/L at 2 weeks, and 265 +/- 29 micrograms/L at 4 weeks; P < 0.05). MK-677 produced significant increases in fasting glucose (5.4 +/- 0.3 to 6.8 +/- 0.4 mmol/L at 4 weeks; P < 0.01 vs. baseline) and IGF-binding protein-3. Circulating cortisol concentrations did not change, and PRL concentrations increased 23%, but remained within the normal range. Once daily treatment of older people with oral MK-677 for up to 4 weeks enhanced pulsatile GH release, significantly increased serum GH and IGF-I concentrations, and, at a dose of 25 mg/day, restored serum IGF-I concentrations to those of young adults.

 

[BadassBlues]

Lets put this aspect to rest regarding the intended use of MK 677 at low doses for cycled theraputic benefits for health extension.

A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly

Acromegaly is an endocrine disorder characterized by dysregulated hypersecretion of growth hormone (GH), leading to an overproduction of insulin-like growth factor 1 (IGF-1). The etiology is usually a GH-secreting pituitary adenoma with the resultant ...

www.ncbi.nlm.nih.gov

Definition and epidemiology

Acromegaly is an uncommon hormonal disorder characterized by excess secretion of GH by a pituitary adenoma, subsequently leading to tissue overgrowth [5]. Considering acromegaly is a rare disease, extensive research is required to generate reliable epidemiological data. Most studies have recorded a prevalence between 2.8 and 13.7 cases per 100,000 persons [6,7] and an incidence between 0.2 and 1.1 cases per 100,000 persons [7]. According to a systematic review and meta-analysis in 2021, the pooled prevalence was 5.9 per 100,000 persons, while the incidence rate was 0.38 cases per 100,000 person-year [8]. The median age at diagnosis is around the fifth decade of life, which ranges between 40.5 and 47 years [9].

Pathophysiology

Acromegaly, in more than 95% of cases, is caused by a benign GH-producing pituitary adenoma [10]. However, exceedingly rare cases of malignant pituitary tumors are documented in the literature [10]. Some other etiologies include hypothalamic tumors (gangliocytoma, hamartoma, and glioma) and ectopic neuroendocrine tumors (pancreatic and bronchial carcinoid tumors), which stimulate excess secretion of GH by the pituitary somatotrophs [3,11]. In addition, acromegaly is also associated with some disorders such as the Carney complex (CNC), McCune-Albright syndrome (MAS), and multiple endocrine neoplasia (MEN) type 1 and 4 [3,11].

In short, the chances of acquiring Acromegaly from small doses of MK 677 taken in cycles is absolutely nil. To add to that, unless you are doing something to increase IGF-1 to superphysical levels for a highly extended period of time, your chances of getting Acromegaly are also nil.

We can now move on from this aspect of the topic.

 

[t_spacemonkey]

A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear

Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is not a clear relationship between the levels of these hormones and stress-associated mental illnesses such as post-traumatic stress ...

www.ncbi.nlm.nih.gov

difficult to draw clear conclusions, but
Repeated activation of ghrelin receptors in non-stressed animals significantly enhances fear learning without elevating HPA stress hormones, while systemic blockade of the ghrelin receptor during chronic stress prevents stress-related enhancement of fear, even in the presence of elevated adrenal stress hormones.
and the activator they used was mk677

 

[BadassBlues]

A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear

Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is not a clear relationship between the levels of these hormones and stress-associated mental illnesses such as post-traumatic stress ...

www.ncbi.nlm.nih.gov

difficult to draw clear conclusions, but
Repeated activation of ghrelin receptors in non-stressed animals significantly enhances fear learning without elevating HPA stress hormones, while systemic blockade of the ghrelin receptor during chronic stress prevents stress-related enhancement of fear, even in the presence of elevated adrenal stress hormones.
and the activator they used was mk677

Interesting study. Possibly a link to some evolutionary response to stress designed as a separate pathway from the HPA axis as a way of imprinting the memory of a stressful event to protect from future perils of the same type?

 

[Guided_by_Voices]

Interesting study. Possibly a link to some evolutionary response to stress designed as a separate pathway from the HPA axis as a way of imprinting the memory of a stressful event to protect from future perils of the same type?

There is a book called Doves, Diplomats and Diabetes that goes into great detail on this however I just checked and it is crazy expensive. If you search the Superhumanradio site there is an interview with the author that talks about how situations like hunger can change the perception of fear.

 

[Dr.V.P.C.]

I have some girls on even 5mg/day doing great .

 

[Fernando Almaguer]

I have some girls on even 5mg/day doing great .

imaporelin would be a safer choice.

 

[BadassBlues]

imaporelin would be a safer choice.

This drug was developed for the purpose of treating adolescents, the safety and efficacy has been proven in many clinical trials and has proven to be very safe for long term use.

 

[BadassBlues]

I am ready to start this @12.5 mg per day. I wanted to finish my cycle of Ipam before starting on the MK 677.

@BigTex @Nelson Vergel

I want to get preliminary labs done to get a baseline and then test again after 8 weeks. What labs should I have done?

 

[BigTex]

Depends on what you are wanting to see. I would get GH, IGF-1 and glucose.

 

[BadassBlues]

Depends on what you are wanting to see. I would get GH, IGF-1 and glucose.

Just looking for the overall effect after 8 weeks.

 

[BigTex]

Seems the things looked at in research were GH, IGF-1 and IGF binding protein-3 levels. Also cortisol, LDL. Of course GH, IGF-1 and IGF binding protein-3 should increase and LDL and cortisol should decrease. Blood glucose readings might be good to look at.

If you have a fitness watch, you might get a baseline average of your nightly sleep score and then do the same during the 8 weeks you plan on being on MK677. An increase n GH should increase you sleep score. Even a 3 site skin fold caliper reason would be cool.

 

[BadassBlues]

Day 2, interesting and unexpected. I noticed a very subtle effect on mood and overall sense of well being. It really hit me today while working. I think at a higher dose, this would be sedative rather than calming which is a common side effect of GH.

I have not noticed any difference yet in sleep quality.

 

[Fernando Almaguer]

Just to share I am on imaporelin and semorelin combo from Revive RX pharm. here in Houston.

I am sleeping better, at least I think from increase dreaming and very lucid ones at that. I notice come fat loss and a calm feeling of well-being. Which could be coming from better sleep. I use a cpap also.

 

[BadassBlues]

There is a definite effect on mood, it's a subtle, overall sense of well being. Anxiety is greatly diminished. Even after my gigantic iced coffee (which I should avoid, but I don't), which usually turns me into a raging maniac, I just feel at ease and happy.

Nagging pain in my wrist and shoulder are also gone. @BigTex Have you experienced any effect on pain relief?

A Systematic Review of Growth Hormone in Pain Medicine: From Rodents to Humans

AbstractObjective. Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This revie

academic.oup.com

Abstract​

Objective
Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This review aims to examine the potential molecular mechanisms through which GH-related signaling modulates sensory hypersensitivity in rodents, the clinical pharmacology of GH, and the clinical evidence of GH treatment for several common pain syndromes.
Methods
A search was conducted using the PUBMED/MEDLINE database, Scopus, and the Cochrane library for all reports published in English on GH in pain management from inception through May 2018. A critical review was performed on the mechanisms of GH-related signaling and the pharmacology of GH. The levels of clinical evidence and implications for recommendations of all of the included studies were graded.
Results
The search yielded 379 articles, of which 201 articles were deemed irrelevant by reading the titles. There were 53 reports deemed relevant after reading abstracts. All of these 53 articles were retrieved for the analysis and discussion.
Conclusions
Dysfunction of the GH/insulin-like growth factor 1 (IGF-1)/ghrelin axis was linked to hyperalgesia and several common clinical pain syndromes. Low levels of GH and IGF-1 were linked to pain hypersensitivity, whereas ghrelin appeared to provide analgesic effects. Pretreatment of GH reversed mechanical and thermal hypersensitivity in an animal model of inflammatory pain. Clinical trials support GH treatment in a subgroup of patients with fibromyalgia syndrome (level of evidence: 1B+) or chronic lower back pain syndrome (level of evidence: 2C+).

This is the only new variable, and the changes are noticeable. But, this is just my personal perspective, ymmv.

 

[BigTex]

There is a definite effect on mood, it's a subtle, overall sense of well being. Anxiety is greatly diminished. Even after my gigantic iced coffee (which I should avoid, but I don't), which usually turns me into a raging maniac, I just feel at ease and happy.

Nagging pain in my wrist and shoulder are also gone. @BigTex Have you experienced any effect on pain relief?

Absolutely no relief. The only thing that seems to slightly help is Celebrex as long as I use it every other day. But even that , the relief is very little.

What is most likely happening is the GH increases from the MK is also increasing your IGF-1 levels. IGF-1 has been show to have an anti-inflammatory effect.

 

[Gman86]

There is a definite effect on mood, it's a subtle, overall sense of well being. Anxiety is greatly diminished. Even after my gigantic iced coffee (which I should avoid, but I don't), which usually turns me into a raging maniac, I just feel at ease and happy.

Nagging pain in my wrist and shoulder are also gone. @BigTex Have you experienced any effect on pain relief?

A Systematic Review of Growth Hormone in Pain Medicine: From Rodents to Humans

AbstractObjective. Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This revie

academic.oup.com

Abstract​

Objective
Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This review aims to examine the potential molecular mechanisms through which GH-related signaling modulates sensory hypersensitivity in rodents, the clinical pharmacology of GH, and the clinical evidence of GH treatment for several common pain syndromes.
Methods
A search was conducted using the PUBMED/MEDLINE database, Scopus, and the Cochrane library for all reports published in English on GH in pain management from inception through May 2018. A critical review was performed on the mechanisms of GH-related signaling and the pharmacology of GH. The levels of clinical evidence and implications for recommendations of all of the included studies were graded.
Results
The search yielded 379 articles, of which 201 articles were deemed irrelevant by reading the titles. There were 53 reports deemed relevant after reading abstracts. All of these 53 articles were retrieved for the analysis and discussion.
Conclusions
Dysfunction of the GH/insulin-like growth factor 1 (IGF-1)/ghrelin axis was linked to hyperalgesia and several common clinical pain syndromes. Low levels of GH and IGF-1 were linked to pain hypersensitivity, whereas ghrelin appeared to provide analgesic effects. Pretreatment of GH reversed mechanical and thermal hypersensitivity in an animal model of inflammatory pain. Clinical trials support GH treatment in a subgroup of patients with fibromyalgia syndrome (level of evidence: 1B+) or chronic lower back pain syndrome (level of evidence: 2C+).

This is the only new variable, and the changes are noticeable. But, this is just my personal perspective, ymmv.

What dose of mk u taking again? And what time of day do u take it?

any water weight/ bloating from what u can tell so far?