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Melatonin + MK 677

Just to clarify, look at the diagrams in the third excerpt. The igf1/igf1bp3 ratio was reduced by both a decrease in igf1 and an increase in igfbp3 which is interesting. So Mike was correct in saying melatonin increased igf1bp3. I was incorrect in saying it didn't. However it did decrease igf1. Does this mean it inhibited somatostatin or not, I'm not sure that wasn't something they looked at. However I wouldn't be looking at melatonin for a gh/igf increase. MK677 increases both already including binding protein 3, because they go hand in hand.
 
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Can you share these studies with me? I haven't seen them. And I'll say it again, just because something may inhibit somatostatin it doesn't mean GH will be released. Somatostatin (GHIH) and GHRH work at the somatotropes, one inhibits release one initiates release. Just because one is not present or its actions are inhibited doesn't mean the opposite will occur. You can't just think that way in my opinion. The study I am quoting directly looked at igf1/igfbp3, this is not an assumption or some "connection" based on a theory. This was the case in both models that were conducted part of the study. It makes sense that something that would have anticancer properties would lower igf, think metformin, etc.

I'm searching and it was done with hamsters, not humans.

https://www.ncbi.nlm.nih.gov/pubmed/1709150

Another text:

"In a study by Lee and colleagues, varying doses of melatonin were administered following focal ischemia in rats. Doses of melatonin were administered at 7 a.m. and 7 p.m. IGF-1 was shown to be significantly increased in the gastrocnemius and soleus muscles in the multiple dose group. Both MaFbx/MuRF1 were also shown to be down-regulated in multiple doses of melatonin including the multiple does group. Additionally, increases in fast and slow muscle isoforms were shown to increase with melatonin. In the gastrocnemius, the 7 a.m. and multiple dose group showed improvements in muscle fiber size in all muscle types. In the soleus muscle, the 7 a.m. group showed increases in all muscle fiber types. The results of this study suggest that melatonin has the potential to upregulate the anabolic hormone IGF-1 as well as increase size in various muscle fiber types."

And this study with young people:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174513/
 
Thanks for posting these. Reading through the last one which is most complete. Looks like there is some increase in GH and decrease in somatostatin, however IGF1 was not increased which is a tell tale of how effective the rise in GH was. Basically, it's not enough to do much of anything.
 
So if you had to choose between melatonin and huperzine, would you go for the latter?

Well i've already order melatonin to use with DAC+MK-677, now i dont know if i should use it when i start that.
 
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Below are just a few of the studies showing that melatonin increases GH, IGF-1 and IGFBP-3 levels, while also reducing cortisol levels. Researchers also speculate that melatonin may increase GH/IGF-1 levels through more mechanisms that just somatostatin inhibition (optimization of circadian rhythms and other unknown mechanisms) and that melatonin plays an important role in GH release. Lastly, and even more importantly, is that melatonin has already been PROVEN to build muscle and decrease bodyfat--significantly--in clinical studies (see below).

It seems that the last "study" that was posted, which showed that melatonin did not increase IGF-1 levels, was done in animals. This fact wasn't disclosed prior to its posting...and it could have led people astray if another member hadn't pointed that out. For some reason, certain people seem to be attempting to undermine the value of MK-677 as a stacker with MK-677, despite the overwhelming and undeniable amount of evidence showing how beneficial it truly is. In order to avoid being duped by those with possible agendas, we all need to do our own research...because it is fairly easy to be "tricked" with an inapplicable study if we aren't paying attention. If we want the truth, we need to evaluate all of the available research, at which point it becomes very obvious that melatonin provides a lot of benefits directly applicable to bodybuilders and is in many ways complimentary to MK-677 or any other GH releasing agent.

The bottom line is that melatonin has a ton of research supporting its ability to increase GH, IGF-1, and IGFBP-3 levels, while also decreasing fat mass, increasing lean mass, reducing cortisol levels, bolstering the circadian rhythm (which in itself promotes improved recovery and growth via an increased rate of cellular repair and increased GH/IGF-1 levels, as quality sleep is essential for optimization of the GH/IGF-1 axis and all other bodily functions).

Furthermore, and contrary to a comment made earlier about increased GH levels always being accompanied by an increase in IGFBP-3, this is NOT true. In fact, this doesn't even occur with low-dose MK-677 (5 mg), which is a much more potent GH releasing agent than melatonin. In one study evaluating the effects of MK-677 at both 5 mg and 25 mg, only the 25 mg dose caused an increase in IGFBP-3 levels, but NOT the 5 mg increase, despite the 5 mg dose causing a significant increase in GH levels. This is proof that just because a compound may cause an increase in GH levels (even a substantial increase), it does NOT necessarily lead to a further increase in IGFBP-3 levels. This means that melatonin's ability to increase IGFBP-3 levels is not simply the "inevitable result" of its ability to increase GH levels, but a characteristic specific to melatonin, as even more powerful GH releasing agents (such as 5 mg of MK-677) does not increase IGFBP-3 levels.

Guys, if anyone here still doubts the ability to MK-677 to significantly contribute to recovery, growth, and fat loss, just read the research. As mentioned above, there are even studies which PROVE that melatonin builds muscle and decreases bodyfat...significantly! Melatonin is a cheap and effective way to get more out of our bodybuilding efforts.



Note: In one of the studies below (Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females) I provided only part of the available text. The entire document was multiple pages long and went in depth regarding the study parameters and a bunch of other stuff that wasn't relevant, so I included only the information being discussed here (namely the study results). If anyone wants to read the entire document, they can copy & paste the title of the study and Google it.



Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone.

Valcavi R1, Zini M, Maestroni GJ, Conti A, Portioli I.
Author information
Abstract

OBJECTIVE: There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release.

DESIGN: The study consisted of four protocols carried out during the afternoon hours. Study 1: oral melatonin (10 mg) or placebo were administered 60 minutes prior to GHRH (100 micrograms i.v. bolus). Study 2: GHRH (100 micrograms i.v. bolus) or placebo were administered at 0 minutes; oral melatonin or placebo were given at 60 minutes and were followed by a second GHRH stimulus (100 micrograms i.v. bolus) at 120 minutes. Study 3: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions. Study 4: placebo; oral melatonin (10 mg); oral pyridostigmine (120 mg); melatonin (10 mg) plus pyridostigmine (120 mg) were administered on separate occasions 60 minutes prior to a submaximal dose (3 micrograms i.v. bolus) of GHRH.

SUBJECTS: Four groups of eight normal male subjects, ages 22-35 years, were randomly assigned to each protocol.

MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals.

RESULTS: Oral melatonin administration had a weak stimulatory effect on GH basal levels. Prior melatonin administration approximately doubled the GH release induced by supramaximal (100 micrograms) or submaximal (3 micrograms) doses of GHRH. Melatonin administration restored the GH response to a second GHRH challenge, given 120 minutes after a first GHRH i.v. bolus. The GH releasing effects of pyridostigmine, either alone or followed by GHRH, were greater than those of melatonin. However, the simultaneous administration of melatonin and pyridostigmine was not followed by any further enhancement of GH release, either in the absence or in the presence of exogenous GHRH.

CONCLUSIONS: Our data indicate that oral administration of melatonin to normal human males increases basal GH release and GH responsiveness to GHRH through the same pathways as pyridostigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release, although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.






Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women: A randomized placebo-controlled trial.

Amstrup AK1, Sikjaer T1, Pedersen SB1,2, Heickendorff L3, Mosekilde L1, Rejnmark L1,2.
Author information
Abstract

OBJECTIVE: Apart from regulating the circadian rhythm, melatonin exerts a variety of actions in the living organism. Among these functions, melatonin is believed to have a positive effect on body weight and energy metabolism. So far, the evidence for this relies mainly on animal models. In this study, we aimed to determine the effects of melatonin on body composition, lipid and glucose metabolism in humans.

DESIGN/METHODS: In a double-blind, placebo-controlled study, we randomized 81 postmenopausal women to 1 year of treatment with melatonin (1 or 3 mg nightly) or placebo. Body composition was measured by DXA. Measures were obtained at baseline and after 1 year of treatment along with leptin, adiponectin and insulin. Markers of glucose homeostasis were measured at the end of the study.

RESULTS: In response to treatment, fat mass decreased in the melatonin group by 6·9% (95% CI: 1·4%; 12·4%, P = 0·02) compared to placebo. A borderline significant increase in lean mass of 5·2% was found in the melatonin group compared to placebo (3·3%, (IQR:-1·7; 6·2) vs -1·9%, (IQR: -5·7; 5·8), P = 0·08). After adjusting for BMI, lean mass increased by 2·6% (95% CI: 0·1; 5·0, P = 0·04) in the melatonin group. Changes in body weight and BMI did not differ between groups. Adiponectin increased borderline significantly by 21% in the melatonin group compared to placebo (P = 0·08). No significant changes were observed for leptin, insulin or markers of glucose homeostasis.

CONCLUSION: Our results suggest a possibly beneficial effect of melatonin on body composition and lipid metabolism as 1 year of treatment reduces fat mass, increases lean mass and is associated with a trend towards an increase in adiponectin.



Melatonin reduces cortisol response to ACTH in humans.
[Article in Spanish]
Campino C1, Valenzuela F, Arteaga E, Torres-Farfán C, Trucco C, Velasco A, Guzmán S, Serón-Ferré M.
Author information
Abstract

BACKGROUND: Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland.

AIM: To assess if the human adrenal gland expresses melatonin receptors and if melatonin affects cortisol response to ACTH in dexamethasone suppressed volunteers.

MATERIAL AND METHODS: Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cancer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse TranscriPtase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled trial) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day, at 08:00 h, an i.v. line was inserted, at 08:30 h, and after a blood sample, subjects ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1 microg/1.73 m2 body surface area) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay.

RESULTS: The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestion reduced the cortisol response to ACTH from 14.6 +/- 1.45 microg/dl at 60 min in the placebo group to 10.8 +/- 1.2 microg/dl in the melatonin group (p < 0.01 mixed model test). It did not affect other steroid hormone levels and abolished the morning physiological decline of prolactin.

CONCLUSIONS: The expression of MT1 melatonin receptor in the human adrenal, and the melatonin reduction of ACTH-stimulated cortisol production suggest a direct melatonin action on the adrenal gland.




Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females

Erika Nassar,1 Chris Mulligan,2 Lem Taylor,3 Chad Kerksick,4 Melyn Galbreath,1 Mike Greenwood,1 Richard Kreider,1 and Darryn S Willoughbycorresponding author1,5
Author information ► Article notes ► Copyright and License information ►
This article has been cited by other articles in PMC.
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Abstract
Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin (SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females (n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo. After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min, at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1, and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for IGF-1 (Note: This lack of a IGF-1 elevating effect is attributable to the study's design. Namely, it involved only a single dose of melatonin, which does not increase GH levels for long enough to produce a measurable increase in IGF-1 levels. Had GH levels remained elevated for longer, such as with daily dosing over an extended period of time, IGF-1 levels would have risen, just as they always do during periods of sustained GH elevation). However, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively impacts GH levels in a manner not entirely dependent on SST.

In males, 5.0 mg melatonin resulted in the greatest increase in serum GH during the pre-exercise period (157% increase from baseline), whereas in the post-exercise period both 0.5 mg (106% increase from baseline) and 5.0 mg (132% increase from baseline) melatonin effectively increased GH compared to placebo. Interestingly, during the pre-exercise period, we observed average (± SD) peak GH values to occur at 45 ± 4.5 and 40 ± 3.2 minutes, respectively, for the 0.5 mg and 5.0 mg groups. However, during the post-exercise period, we observed average peak GH values to occur at 25 ± 2.8 and 23 ± 2.2 minutes, respectively, for the 0.5 mg and 5.0 mg groups (Figure ​(Figure2).2).

In males, 5.0 mg melatonin resulted in the greatest decrease in serum SST during the pre-exercise period (164% increase from baseline) while 0.5 mg melatonin decreased 70% from baseline, whereas in the post-exercise period both 0.5 mg (44% decrease from baseline) and 5.0 mg (76% decrease from baseline) melatonin effectively decreased SST compared to placebo. Interestingly, during the pre-exercise period, we observed average (± SD) peak decreases in SST values to occur at 28 ± 5.7 and 33 ± 6.4 minutes, respectively, for the 0.5 mg and 5.0 mg groups. However, during the post-exercise period, we observed average peak decreases in SST values to occur at 14 ± 3.6 and 19 ± 4.2 minutes, respectively, for the 0.5 mg and 5.0 mg groups (Figure ​(Figure66).

In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both 0.5 mg and 5.0 mg melatonin appears to positively impact GH levels in a manner not entirely dependent on decreases in SST. Relative to the response in females, it appears that both melatonin and resistance exercise elicits a greater GH response in males.






Melatonin increases serum growth hormone and insulin-like growth factor I (IGF-I) levels in male Syrian hamsters via hypothalamic neurotransmitters.

Vriend J1, Sheppard MS, Borer KT.
Author information
Abstract
In male Syrian hamsters daily evening melatonin injections resulted in increased circulating levels of growth hormone (GH), as well as a modest increase in body weight. A substantial increase in serum levels of insulin-like growth factor I (IGF-I) was observed in all hamsters receiving evening injections of melatonin for 10 weeks. The melatonin-induced increase in serum IGF-I levels was interpreted as a result of increased release of GH during the 10 week period of melatonin administration. The increase in serum GH and IGF-I was associated with significantly decreased hypothalamic turnover of norepinephrine (NE). Since blocking NE synthesis with alpha methyl-p-tyrosine reduced serum GH, the melatonin-induced increase in GH could not readily be attributed to decreased NE turnover. Highly significant increases in 5-hydroxyindole acetic acid (5HIAA) concentrations and in ratios of 5HIAA to serotonin (5HT) were noted in extracts of hypothalamus and in extracts of brain stem, suggesting a serotonergic component to melatonin-induced increase in GH-induced IGF secretion and subsequent growth.
 
Thanks for posting these. Reading through the last one which is most complete. Looks like there is some increase in GH and decrease in somatostatin, however IGF1 was not increased which is a tell tale of how effective the rise in GH was. Basically, it's not enough to do much of anything.

Bro, you keep changing your tune.

First you say I am wrong on both counts.

Then, after you realize you made a mistake you change your position and say that I am right on one count and you are right on one count.

Then, after another member points out that the study you posted isn't applicable to humans, you reluctantly admit that I was right on both counts, but instead of simply dropping it there you go on to say that IGF-1 levels didn't increase, so its ability to increase GH levels and decrease somatostatin was insignificant (thereby attempting to undermine its value to the point of worthlessness).

Well, you are wrong there too. Read through the studies I posted above. No one ever claimed melatonin was going to blow our GH, IGF-1, and IGFBP-3 levels through the roof, but it does increase levels of those hormones through multiple mechanisms (both direct and indirect) in ways that are complimentary to MK-677 use. Furthermore, the research is clear that melatonin contributes to recovery, growth and fat loss in several ways...ad not just through increases in GH, IGF-1, and IGFBP-3 levels. Its pro-bodybuilding effects include:

* Increased GH levels

* Increased IGF-1 levels

* Increased IGFBP-3 levels

* Decreased somatostatin levels

* Optimization of the circadian rhythms (which not only promotes increased GH release, but increases the rate of cellular repair as well; super important for bodybuilders)

* Decreased cortisol levels

* Contrary to your claim, increases in GH are not always accompanied by further increases in IGFBP-3 levels, as not even MK-677 increases IGFBP-3 levels at 5 mg/day, and MK-677 is a significantly more powerful GH increasing drug than melatonin. However, melatonin does have this effect.

* Lastly, researchers also believe that melatonin increases GH levels through mechanisms other than just somatostatin inhibition (see study below)

* Even better, there are now studies which PROVE that melatonin builds muscle and decreases bodyfat...significantly, in NON-weight trainers!




It is the sum total of all these benefits, along with its SUPER CHEAP price, that makes melatonin a great stacker with MK-677 or any other GH releasing agent. Is it going to double your GH, IGF-1, and IGFBP-3 levels when someone is already taking taking MK-677? Of course not, but will it help optimize GH, IGF-1, and IGFBP-3 production in several ways, while also increasing lean muscle and decreasing bodyfat through multiple mechanisms.

Melatonin is a nice, complimentary addition to GH peptide/secretagogues...and one of the cool things about it (aside from its dirt cheap price) is that it can be used long-term without causing any ill effects on our health or producing unwanted side effects. In fact, it provides numerous health benefits...and with modern Americans/Europeans being deficient in melatonin due to the presence of multiple disruptive sleep factors, this is just one more reason to supplement with this hormone.
 
Mike, I was having a discussion and asked for the studies. I wasn't talking in absolutes. You just reposted the same studies that were posted. Bottom line is melatonin does not appear to have significant impact on these hormones. You flamed me for using 5mg MK677 saying it wasn't a "bodybuilding" dose and rises from that dosage are insignificant for what we are after. You said the same about 1-2iu gh. Now you're trying to convince me these insignificant effects are worthwhile? You're talking out of both sides of your mouth. My message has been the same here from the start regarding MK677 (powerful) and these other "ancillary" supps (insignificant) when it comes to GH/IGF.

Let's just be real here, I would personally not be looking at melatonin in the aspect of gh/igf increase. Nor should anyone else. That's not what it does or what it's for. I use melatonin prebed. Many benefits but not gh and igf benefits. If anything up your MK677 dose 5mg and it would yield better effects then this. We are talking along the lines of adding tribulus to exogenous testosterone versus increasing your testosterone dosage. Now which one is actually going to be effective?
 

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