Long acting Ghrelin mimetics (MK-677) = brain detrimental

kall

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This is a fantastic datbtrue article about the damage that MK-677 can cause to the brain.
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How do we lose GHSR1a (Ghrelin receptor's) in the brain?

It appears that transient stimulation such as what one would get with GHRPs (GHRP-2, GHRP-6, Ipamorelin, Hexarelin) leads to a rapid desensitization and internalization of the receptors in the brain and this is a good thing. On the other hand administration of long acting Ghrelin-memetic (ibutamoren mesylate (MK-0677) likely leads to a habitual loss receptor status. This is a very bad thing.

Ghrelin mimetics (or agonists) do more that create growth hormone

I'm not sure most people understand that the Ghrelin mimetics do more than create GH. The Growth hormone secretagogue receptor 1a (GHSR1a) is the primary receptor for Ghrelin and the Growth Hormone Releasing Peptides as well as the non-peptide Growth Hormone Secretagogues. There are subtype receptors that both acyl-Ghrelin and the GHRPs bind to that the non-peptide GHS's do not. However the primary receptor is the GHSR1a and it is located on somatotrophs (GH-releasing cells) in the anterior pituitary. Ghrelin or a GHRP or non-peptide GHS bind to these receptors sometimes in concert with Growth Hormone Releasing Hormone (GHRH) and cause growth hormone release.

However GHSR1a are located in all sorts of non-pituitary tissue. When Ghrelin or GHRP-2 or GHRP-6 or Ipamorelin or Hexarelin bind to these receptors in these tissues they generally have positive effects. In some instances they can increase local acting growth hormone in those tissues. Their receptor interaction is transient because peptides break down. They do not over-stimulate receptors on the heart, lung, spleen, muscle or brain.

GHS molecules that do not break down readily cause non-physiological states. They overstimulate and in regard to the brain they create chronic stresses that are potentially neurologically damaging or altering of physiology that can lead to states of unhealth.

Ghrelin in the brain is a stress hormone that acts independent of cortisol. Whether this activity is good or bad depends on how long the GHSR1a is activated.

Brain GHSR1a activation is biphasic:

Acute Ghrelin or agonists (GHRP-2, Ipamorelin, GHRP-6, Hexarelin):
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- anti-depressive
- anti-anxiety
- protective of stress
- potentially neurologically protective

Chronic (non-pulsed) Ghrelin agonists (ibutamoren mesylate (MK-0677) :
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- depression producing
- anxiety producing
- fear conditionoing producing effects of chronic stress
- potentially neurologically damaging

It's important to understand what follows. A tip toe through the literature often reveals the good that Ghrelin produces. However those studies used acute methodologies.

The recent study A ghrelin–growth hormone axis drives stress-induced vulnerability to enhanced fear, RM Meyer, Molecular Psychiatry (2014), 1284 – 1294 distinguishes it's results by using a low dose but longer lasting Ghrelin mimetic (ibutamoren mesylate (MK-0677)) in creating a chronic situation. I will elaborate from the study...
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GH is created not only in the pituitary but also in brain regions such as basolateral complex of the amygdala (BLA) . The growth hormone secretagogue receptor 1a (GHSR1a) is found in the BLA. This is the region that regulates emotional states such as fear.

Over-expression of recombinant GH in the BLA does not alter fear acquisition but it does enhance long-term fear memory that is created by chronic Ghrelin.

Chronic Ghrelin or long-lasting agonists such as ibutamoren mesylate (MK-0677) can create the fear/stress response, in the absence of an externally stressful event (in other words the chronic Ghrelin engenders the stressful state) and the presence of GH can amplify it.

Prolonged stress "load" and neuronal dysfunction are correlated. So one would expect chronic Ghrelin to lead to neuronal dysfunction.

Again it is important to remember that GHRPs do more than increase GH release from GH-releasing cells in the pituitary. They also do so peripherally. By peripherally I mean tissue that generally does not release factors systemically but rather uses what it makes locally within the neighboring tissue (paracrine). That tissue does not need to be all of the same type. For instance bone and muscle sometimes share locally released factors.

Not all GHRPs produce the same peripheral GH. They appear to differ somewhat in their ability to bring about GH locally via GHSR1a (growth hormone secretagogue receptor 1a).

In this RM Meyer study stimulation of the GHSR1a in BLA cells by ibutamoren mesylate (MK-0677) led to significantly elevated release of brain GH. Antagonizing the GHSR1a to prevent it's activation prevents the fear conditioning stress response.

However chronic stimulation of the GHSR1a led to the severe brain stress-enhancing effects.

How would Ghrelin or ibutamoren mesylate (MK-0677 readily crosses the blood–brain barrier and has a half-life of >6h) would be available in the amygdala (BLA):
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"Ghrelin may also be synthesized by small populations of neurons in the hypothalamus, the cerebral cortex and the brainstem, where it may act as a paracrine hormone rather than being secreted into the blood stream. However, immunoreactive ghrelin-containing fibers have never been reported in amygdala. Thus, it seems that the most likely source of bioactive ghrelin affecting fear lies in the periphery, although a role for centrally derived ghrelin cannot be fully eliminated."

Thus higher amounts or long-lasting agonists would likley supply the activation of GHSR1a in the amygdala (BLA). Peptidyl Growth Hormone Releasing Hormone are short lived and would be expected to exert positive effects (as discussed in the follow on sections) and not likely be, if used physiologically, capable of the detrimental effects.

Whereas non-peptidyl longer lived agonists would be expected to exert negative effects and as the RM Meyer study demonstrates are capable of the detrimental effects.

Most of the Discussion from A ghrelin–growth hormone axis drives stress-induced vulnerability to enhanced fear, RM Meyer, Molecular Psychiatry (2014), 1284 – 1294


They found that the
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...effects of stress are not simply downstream from glucocorticoids or adrenal catecholamines. We also show that increased ghrelin receptor activity is sufficient and necessary for stress-enhanced fear and is dissociable from HPA activity. Repeated activation of ghrelin receptors in nonstressed animals significantly enhances fear learning without elevating HPA stress hormones, whereas systemic blockade of the ghrelin receptor during chronic stress prevents stress-related enhancement of fear, even in the presence of elevated adrenal stress hormones We demonstrate that the amygdala, a brain region that displays enhanced function in chronically stressed animals and in patients with trauma-related disorders, is likely the locus of the fear enhancing effects of repeated ghrelin receptor stimulation. Finally, we show that GH, a downstream effector of ghrelin receptor activation, is increased in the BLA by chronic stress, is sufficient to enhance fear learning and plays a necessary role in the fear potentiating effects of ghrelin. Thus, ghrelin and growth hormone act together in the amygdala to enhance fear.

Our study is the first to explicitly examine the effects of protracted exposure to elevated ghrelin, as observed following chronic stress. We show that there are profound differences in the behavioral consequences of ghrelin exposure following different exposure durations, similar to the cumulative nature of stress. We also provide the first evidence to link prolonged exposure to elevated ghrelin with a specific, detrimental consequence of stress, enhanced fear memory, which typifies trauma-induced anxiety disorders such as PTSD. Because PTSD is a multifaceted disorder producing many symptoms, including those related to avoidance and hyperarousal, it will be interesting to determine whether chronically elevated ghrelin contributes to these sequelae of PTSD in addition to promoting changes in fear learning and memory.

Our study is also the first to show that GH is a critical downstream mediator of the effects of ghrelin in amygdala. Such a relationship between ghrelin and GH has not been described outside of the pituitary.51 We also provide the first evidence to link elevated amygdala GH with chronic stress and enhanced fear memory. Taken together, our data reveal that the amygdala may be especially sensitive to ghrelin-mediated effects of stress because chronic stress amplifies both ghrelin and GH.

In contrast to our findings that link ghrelin to a pathological condition, prior studies have argued that ghrelin promotes adaptive changes during stress, including antidepressant effects ( Lutter M, The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci 2008; 11: 752–753) and reduction in anxiety.(Spencer SJ, Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress. Biol Psychiatry 2012; 72: 457–465) However, these studies are problematic because they either focused exclusively on acute ghrelin manipulations, which we show can have profoundly different effects from repeated ghrelin manipulations or used short- and long-term ghrelin manipulations interchangeably. In addition, the alterations in ghrelin levels were achieved through artificial states: heightened ghrelin levels were attained by extreme food deprivation or a single bolus injection of the short-lived peptide. The antidepressant effect of ghrelin requires extremely high levels of ghrelin, as found in food-restricted rodents after 10–15% weight loss.13 We find that this level of food deprivation leads to increased exploratory motor activity (Supplementary Figure 10; F(1, 13)¼7.51, Po0.05). A recent study has also reported similar motor effects following acute ghrelin manipulations.57 These motor effects can be a significant confound for measures that require locomotor activity, such as social interaction or exploration. Thus, the ghrelin may alleviate the psychomotor effects of depression in a manner similar to amphetamine.58 It is also important to note that the antidepressant effect of ghrelin reported following a single injection of exogenous ghrelin was only a mild improvement of a stressmrelated impairment in social interaction;13 enhanced ghrelin signaling did not promote ‘normal’ function following stress. Indeed, our results reported here are consistent with limited human data showing that patients with treatment-resistant major depressive disorder have higher ghrelin levels than control patients.59

Here we demonstrate changes in endogenous ghrelin following stress and also use a low-dose, long-acting agonist to replicate the naturally occurring ghrelin state. We also provide clear evidence that acute and chronic ghrelin receptor manipulations have profoundly different effects. It is important to note that the changes in fear reported here occurred following small, but persistent, changes in ghrelin signaling, and all were in the absence of any locomotor effects. We suggest that the utility of ghrelin in the stress response may be similar to glucocorticoids: under ‘normal’ conditions, there is an optimal level of the hormone,60 and too little61,62 or too much hormonal signaling16 can lead to dysfunction in neuronal circuits. Repeated activation of ghrelin and glucocorticoid pathways together contributes to stress-induced ‘load’ on the body. In this regard, heightened ghrelin signaling may have both advantageous and undesirable consequences, but these must be carefully considered with respect to the length and level of elevated ghrelin exposure.

It is not clear why acute and repeated ghrelin receptor stimulation have opposite effects on fear learning. Although GHSR1a activation engages excitatory Gq-dependent molecular cascades, GHSR1 also exhibits an extremely high level of constitutive activity in the absence of bound ligand.77 Accordingly, transient stimulation of GHSR1a leads to rapid desensitization and internalization of the receptor that is slow to recover.78 Such a change is consistent with the decreased fear learning we observed 24 h after a single injection of ghrelin receptor agonist. It is also consistent with the observation that transient bath application of ghrelin to lateral amygdala slices leads to decreased excitatory neurotransmission.15 The electrophysiological changes elicited by chronic ghrelin receptor stimulation in amygdala are completely unexplored, but our work suggests that the change must be opposite to that seen after acute ghrelin receptor stimulation. We suggest that the internalization of the ghrelin receptor may habituate63 following either chronic administration of ghrelin receptor agonist or chronic stress exposure. The differences in receptor kinetics following acute versus chronic ghrelin receptor stimulation represent an especially promising area for future research.

Practical notation...

Although the study highlights conditioned fear (term used to describe a cluster of behavioral effects produced when an initially neutral stimulus is paired with an aversive stimulus. A stressfull condition becomes married to the ordinary which in turn evokes a chonic stress response). - The Role of the Amygdala in Fear and Anxiety Annual Review of Neuroscience Vol. 15: 353-375 (Volume publication date March 1992)) it has much wider implications. Those wider implications may not be felt but may increase vulnerability to future disease states.

Pulsed GHRPs or spaced GHRPs give their receptors in the brain time off. Activation of those receptors does not become chronic. This is a good thing especially in the presence of growth hormone. GHRPs or any Ghrelin mimietc such as long-lasting analog have functions independent of growth hormone release. If made available physiologically they can reduce Vascular Stress (reducing insulin resistance) - Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells, M. Iantorno, American Journal of Physiology, vol. 292, no. 3, pp. E756–E764, 2007; act in muscle repair similiar to muscle IGFs - Ghrelin and Des-Acyl Ghrelin Promote Differentiation and Fusion of C2C12 Skeletal Muscle Cells, Nicoletta Filigheddu, MBoC Vol. 18, Issue 3, 986-994, March 2007; acts as an anti-inflammatory - GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia, Miriam Granado, AJP - Endo January 2008 vol. 294 no. 1 E131-E141, exhibit some anti-cancer effects - The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells, Ghe C, Cassoni P, Catapano F, Marrocco T, Deghenghi R, Ghigo E, Muccioli G, Papotti M, Endocrinology 2002, 143, 484–491

However when allowed to activate their receptors beyond their pulsed nature (aside from situations such as drastic calorie deprivation) Ghrelin-mimetics can bring ill effects that may only manifest themselves many years later as a result of increase stress responses that create degeneration.
 

JSTR808

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Since I use a low dose 10mg before bed nightly, I'll be reading this a few times over. Thanks!!!!
 
PeteRyde

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Don't suppose someone could dumb this down a bit. Are we saying taking MK-677 long term will permanently cause increased mental stress?
 

kall

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Don't suppose someone could dumb this down a bit. Are we saying taking MK-677 long term will permanently cause increased mental stress?
" Prolonged stress "load" and neuronal dysfunction are correlated. So one would expect chronic Ghrelin to lead to neuronal dysfunction. "
 

JSTR808

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But I don't see/feel these symptoms at 10mg before bed. Maybe at 20mg, but I think that is too high dose even for a bodybuilding effect in the long run. My .02
 

YoungBodyBuil

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So basically anything that mimics ghrelin... Atroclydes monnieri (may have butchered the spelling) But basically the AI in Letrone, could cause this then?
 

kall

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But I don't see/feel these symptoms at 10mg before bed. Maybe at 20mg, but I think that is too high dose even for a bodybuilding effect in the long run. My .02
I think we are not able to feel the symptoms, but if mk-677 is taken every day the neurons will be under chronic huge amount of stess and potentially being damaged.

So basically anything that mimics ghrelin... Atroclydes monnieri (may have butchered the spelling) But basically the AI in Letrone, could cause this then?
I don't know about Letrone, but keep in mind that a ghrelin agonist is harmful only if it chronically increases ghrelin. A short term increase should be good.
 
ELROCK

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I'll be selling my ghar1ne :)
Lol... I was about to put two bottles up in the auction section just yesterday. Now I may wait a lil because I can see this thread bringing down the value ha
 

JSTR808

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I'll probably switch to 10mg every other day as per Seth Williams. He said he had same benefits at those low doses. I have seen enormous improvements, but then I'm an older athlete. Could age play a role?
 

kall

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Lol... I was about to put two bottles up in the auction section just yesterday. Now I may wait a lil because I can see this thread bringing down the value ha
**** sorry man ahahah

So how long is too long?
We can't know

I'll probably switch to 10mg every other day as per Seth Williams. He said he had same benefits at those low doses. I have seen enormous improvements, but then I'm an older athlete. Could age play a role?
With gh secretagogues I think the older, the better
 

JSTR808

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Heartfelt thanks for the reply. I finally found something that's worked to fix pain in broken hand, damaged tendon in knuckles, shin contusions, rotator cuff injurie from days I used to kickbox. Now I can enjoy my retirement from the sport and heal myself via MK677. But I need to approach in smart manner according to the study.
 
goodvibes

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I read it halfway but my damaged neurons cannot absorb anymore info. Jokes aside that's not good. I loved mk677 but since the stash is running low and they're not really for sale in the market anymore it's good to stop now.
 
NoAddedHmones

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Why has there been close to 20 years of clinical trials in humans and these effects have not been noted nor have the drug trials been stopped...
 

kall

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Why has there been close to 20 years of clinical trials in humans and these effects have not been noted nor have the drug trials been stopped...
But there's no study that analyzed the brain after years of use... I think you can't really feel if you lost some neurons or if you lost 5 IQ points, so patients in the studies never complained about these adverse effects.
And if after 20 years is still not approved for human use there should be a reason...
 

JSTR808

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After combing through with friends, here's the response:
1 The "study" is based on projection not tests.
2 The tests that were quoted were not ot done with MK677, so again the "study" projects the results on to MK677 (which would also imply that MK677 does what it claims).
3. The sum of the "results" quoted as being negative was not reported by people currently using MK677, and quite the opposite: nothing but positive results when dosed properly. ESPECIALLY cognitive function.
Conclussion (so far): makes one project a financial or underlying motive against MK677 to possibly get funding to test a NEW compound which will be projected as "Safe & Effective".
 
Danes

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Don't suppose someone could dumb this down a bit. Are we saying taking MK-677 long term will permanently cause increased mental stress?
First of all, this is just speculation and there are NO human studies proving that.
Compounds work differently in humans and animals.Xylitol is PURE poison for lets say dogs while humans can use it without any problem at all!
Ecdysterone in rats is stronger than most anabolics and even IGF1,DHT +++ but will it be the same in humans? No. The list is ENDLESS.

It is ok to be skeptical etc but there is NO reason to overthing things.
This is overthinking at its best
 
Danes

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So basically anything that mimics ghrelin... Atroclydes monnieri (may have butchered the spelling) But basically the AI in Letrone, could cause this then?
You have bothing to be affraid of.
1. Dose of Atractylodes found in Letrone is not high enough
2. Atractylodes will not secrete Ghrelin directly
 

ericos_bob

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" Prolonged stress "load" and neuronal dysfunction are correlated. So one would expect chronic Ghrelin to lead to neuronal dysfunction. "
Temporary. Neuronal impairment and neuron death are not the same. We have only a finite number of neurons but neuron connections are far more important at least in regard to IQ. Axons and dendrites can be increased until late in life. It's why the brain is often referred to as a muscle. It can be trained and it can recover from chronic stress.
Emotional changes through fear learning due to chronic ghrelin mimetic use may be long lasting. Granted these effects may be reversed. I would er on the side of caution and take breaks from MK use. Cycling MK sounds like a good option to reap the benefits and allow adequate recovery from mental stress. The key is to find the correct balance.
 
Blergs

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Blergs

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No. MK677 and Pralmorelin (oral GHRP2) is not same
why i said "pretty much" it acts as a ghrp and seems to be much easier to find at rc shops.
I havent used the Pralmorelin myself so i cant comment but from the research it seems promising for sure. i just havent seen much feedback on it yet so usually rec the mk since its actions are similar.
 
Danes

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why i said "pretty much" it acts as a ghrp and seems to be much easier to find at rc shops.
I havent used the Pralmorelin myself so i cant comment but from the research it seems promising for sure. i just havent seen much feedback on it yet so usually rec the mk since its actions are similar.
You are totaly right about MK677 and its function as GHRP . Not to mention how easier is to find it compared to Pralmorelin. But honestly, Pralmorelin would provide much better effects but the sides would be stronger too.
 
Danes

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Using GHRP such as MK677 in just 2 months is pretty much useless for bodybuilding. I said from the beginning, longer you take, the better effect would be and studies are proving it
 
StanleyG

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Using GHRP such as MK677 in just 2 months is pretty much useless for bodybuilding. I said from the beginning, longer you take, the better effect would be and studies are proving it
This is definitely true and I have been saying so as well all along. My personal experience is bearing it out also. It should be of no surprise. Its just like GH, there isnt much benefit to running it for just 8 weeks.
The prob with mk is early on it was avail as a supp and the supp companies did their usual BS hocus pocus marketing nonsense and gave people the wrong impressions as to what they could expect and how best to use mk. Now that they really no longer carry it and time is going on the truth about the best protocols and true expectations are coming out, which is a good thing.
 

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This is definitely true and I have been saying so as well all along. My personal experience is bearing it out also. It should be of no surprise. Its just like GH, there isnt much benefit to running it for just 8 weeks.
The prob with mk is early on it was avail as a supp and the supp companies did their usual BS hocus pocus marketing nonsense and gave people the wrong impressions as to what they could expect and how best to use mk. Now that they really no longer carry it and time is going on the truth about the best protocols and true expectations are coming out, which is a good thing.
I've been running it for a week only so far and I can't speak highly enough of it. Came in liquid form, and I'm at 30mg/day. You all think that's safe? I only get some tingling in the hands, not much which I took as a sign i had a legit product only and have been able to ignore it since.

I'm going to switch to 5 on/2 off to start with. Had anyone adjusted their dosing based on this article, speculation or not?
 
Danes

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I've been running it for a week only so far and I can't speak highly enough of it. Came in liquid form, and I'm at 30mg/day. You all think that's safe? I only get some tingling in the hands, not much which I took as a sign i had a legit product only and have been able to ignore it since.

I'm going to switch to 5 on/2 off to start with. Had anyone adjusted their dosing based on this article, speculation or not?
Take it everyday! No reason to run 5/2 at all!
Ionger duration = more GH/IGF1
 
StanleyG

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Take it everyday! No reason to run 5/2 at all!
Ionger duration = more GH/IGF1
How do you know this? Perhaps you get the same gh/igf levels at 5on/2off with less side effects from say prolactin. Or (the more likely scenario) over time your igf/gh might actually be lower by not taking 2 days off. You see the body strives to achieve homeostasis and in response to taking the mk it increases the production of ghih, which ultimately lowers gh.
 

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sorry if missed this, but do any of the Acute Ghrelin or agonists come in an Oral form?
 
StanleyG

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MK677 is a chronic agonist. I am wondering if any of the Acute agonists listed (ghrp 2 or 6 for example) at the beginning of this thread are Oral.
There is an oral version of ghrp2. Google Pralmorelin
 
Danes

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How do you know this? Perhaps you get the same gh/igf levels at 5on/2off with less side effects from say prolactin. Or (the more likely scenario) over time your igf/gh might actually be lower by not taking 2 days off. You see the body strives to achieve homeostasis and in response to taking the mk it increases the production of ghih, which ultimately lowers gh.
Prolactin, cortisol etc = no huge issue at all! If you see those studies, even healthy men didnt have 2 days off.
MK677 is NOT increasing GHIH (somatostatin). Studies are proving it and the logic is there. With MK677, longer you take, more GH,IGF1 and IGFBP3 is secreted.The good thing with MK677,is the increase of IGFBP3.more IGFBP3, more IGF1 is carried . (Into the cell and activate the receptor).
Maybe you get the same effect if taking 5 days on and 2 days off, but the halflife is long and even if it had sides, it would not be decreased so much while taking 2 days off.
I really see no point taking 2 days off at all and there is no reason to overthinking some things.
 
Danes

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30mg? Also heard hold it in mouth for a while to aid absorption.
If its good quality, 25mg will actually be enough. MK677 has no issue with absorption so just swallow it.
Dont expect some huge gains from it.
 
StanleyG

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Prolactin, cortisol etc = no huge issue at all! If you see those studies, even healthy men didnt have 2 days off.
MK677 is NOT increasing GHIH (somatostatin). Studies are proving it and the logic is there. With MK677, longer you take, more GH,IGF1 and IGFBP3 is secreted.The good thing with MK677,is the increase of IGFBP3.more IGFBP3, more IGF1 is carried . (Into the cell and activate the receptor).
Maybe you get the same effect if taking 5 days on and 2 days off, but the halflife is long and even if it had sides, it would not be decreased so much while taking 2 days off.
I really see no point taking 2 days off at all and there is no reason to overthinking some things.
Please show me a study that proves with constant use ghih is not increased. I will tell you why I ask and it certainly isnt to bust chops, it goes against the very nature of every single ghrellin mimetic and ghrp in existence EXCEPT for mk if you are correct.
 
Danes

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Please show me a study that proves with constant use ghih is not increased. I will tell you why I ask and it certainly isnt to bust chops, it goes against the very nature of every single ghrellin mimetic and ghrp in existence EXCEPT for mk if you are correct.
Example:
If GHIH was involved, the secretion of GH would decrease longer you use. That is not the case with MK677.
Show me one study where MK677 increase GHIH.
That is why those new "GHRP" are made. They are "smarter". By giving less sides etc.
 
Danes

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I have personaly talked with one of the MK677 developers(at Reverse Pharmacology)and he said very shortly:
"MK677 has ability to bypass the somatostatin barrier by interacting directly with GH receptors".
If he lie, then I lie too. But it is very logical. Like said, longer you take MK677, more secretion of GH is. (IGF1 and IGFBP3 too)
 
StanleyG

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I have personaly talked with of the MK677 developers and he said very shortly:
MK677 has ability to bypass the somatostatin barrier by interacting directly with GH receptors.
If he lie, then I lie too. But it is very logical. Like said, longer you take MK677, more secretion of GH is. (IGF1 and IGFBP3 too)
MK interacts with the ghrellin receptors, not the gh receptors on the anterior pituitary???? so that confuses me...cause it doesnt make any sense
Also gh wouldnt decrease it would just not increase to the level it potentially could man.
 
Danes

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MK interacts with the ghrellin receptors, not the gh receptors on the anterior pituitary???? so that confuses me...cause it doesnt make any sense
Also gh wouldnt decrease it would just not increase to the level it potentially could man.
We shall not overcomplicate things.
All studies on healthy people and patients, it was dosed every day.
It is also proven it works better and better longer its taken. (Every day)

We can speculate about dosing and other factors regarding MK677. But one thing is for sure, it will not elevate Cortisol, prolactin or give other issues like other GHRP/GHRH does :)
 
StanleyG

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We shall not overcomplicate things.
All studies on healthy people and patients, it was dosed every day.
It is also proven it works better and better longer its taken. (Every day)

We can speculate about dosing and other factors regarding MK677. But one thing is for sure, it will not elevate Cortisol, prolactin or give other issues like other GHRP/GHRH does :)
I agree re cortisol, that is documented and proven but I will not jump to the same conclusion re PRL and ghih.
Perhaps I should not jump to the conclusion it does either but as of right now I do not think it can definitively be said it does or does not and the 5on, 2off is working great for me. Maybe for the next 4-5 weeks ill do 7 on and get my 3rd set of BW while taking my mk/cjc stack and see just what happens re gh and igf as well as prl. I wasnt planning on it but inquiring minds want to know!
 
Danes

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I agree re cortisol, that is documented and proven but I will not jump to the same conclusion re PRL and ghih.
Perhaps I should not jump to the conclusion it does either but as of right now I do not think it can definitively be said it does or does not and the 5on, 2off is working great for me. Maybe for the next 4-5 weeks ill do 7 on and get my 3rd set of BW while taking my mk/cjc stack and see just what happens re gh and igf as well as prl. I wasnt planning on it but inquiring minds want to know!
Prolactin will not be an issue at all. Believe me. If you even get any increase, it would not be anything huge. The water retention people get from MK677 is due to sodium intake. As you know, MK677 does increase sodium retention .MK does increase ADH (Vasopressin)and ACTH wich again increase sodium retention in kidneys/water retention. So one should be carefull with sodium intake
 
Danes

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I agree re cortisol, that is documented and proven but I will not jump to the same conclusion re PRL and ghih.
Perhaps I should not jump to the conclusion it does either but as of right now I do not think it can definitively be said it does or does not and the 5on, 2off is working great for me. Maybe for the next 4-5 weeks ill do 7 on and get my 3rd set of BW while taking my mk/cjc stack and see just what happens re gh and igf as well as prl. I wasnt planning on it but inquiring minds want to know!
MK/CJC is perfect stack to be honest. You will get even more out of GHRP when adding GHRH like you do
 
StanleyG

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Prolactin will not be an issue at all. Believe me. If you even get any increase, it would not be anything huge. The water retention people get from MK677 is due to sodium intake. As you know, MK677 does increase sodium retention .MK does increase ADH (Vasopressin)and ACTH wich again increase sodium retention in kidneys/water retention. So one should be carefull with sodium intake
100% agreed re water retention, which is why i resorted to a daily aspirin therapy regiment(82mg/day) which effects vasopressin and offsets the water retention from mk (and pharma gh for that matter)
I tend to agree as far as what i expect re PRL. GHIH is my main concern. Great conversation man. TY for sharing the info/input.
 
Danes

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100% agreed re water retention, which is why i resorted to a daily aspirin therapy regiment(82mg/day) which effects vasopressin and offsets the water retention from mk (and pharma gh for that matter)
I tend to agree as far as what i expect re PRL. GHIH is my main concern. Great conversation man. TY for sharing the info/input.
Ibuprofen (400mg x3) daily will also help with water retention . There is a study proving it :)
No problem man. TY for sharing the info :)
 

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