MK-677 Oral HGH Secretagogue
MK-677 Oral HGH Secretagogue
MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.
AuthorsMurphy MG, et al. Show all Journal
J Clin Endocrinol Metab. 1998 Feb;83(2):320-5.
The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. 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. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean +/- SE; MK-677 group -2.67 +/- 0.40 g/day vs. placebo group -2.83 +/- 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 +/- 0.21 g/day in the MK-677 treatment group compared with -1.48 +/- 0.21 g/day in the placebo group (P < 0.01). MK-677 improved nitrogen balance integrated over the 7 days of treatment; area under the curve day 8-14 nitrogen balance response was +2.69 +/- 5.0 (SE) for MK-677 and -8.97 +/- 5.26 g.day for placebo (P < 0.001). MK-677 produced a peak GH response of 55.9 +/- 31.7 micrograms/L after single dose (day 1 of treatment) and 22.6 +/- 9.3 micrograms/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 micrograms/L (treatment day 7). 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). No significant difference in IGF binding protein-2 was found between the MK-677 and placebo treatments. However, the mean in IGF binding protein-3 for the last 5 days of MK-677 treatment was also significantly increased to 3273 +/- 330 ng/mL (mean +/- SE) compared with placebo 2604 +/- 253 ng/mL (P < 0.01). Neither the serum cortisol nor the PRL response was significantly greater after 7 days of MK-677 dosing compared with 7 days of placebo. MK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences. In conclusion, MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.
MK-677 is a ghrelin memetic like GHRP6 so perfect for the bulk cycle I'm on.
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.
AuthorsNass R, et al. Show all Journal
Ann Intern Med. 2008 Nov 4;149(9):601-11.
Ann Intern Med. 2009 May 5;150(9):654-5; author reply 655.
Ann Intern Med. 2008 Nov 4;149(9):677-9.
Ann Intern Med. 2009 May 5;150(9):653-4; author reply 655.
Ann Intern Med. 2009 May 5;150(9):654; author reply 655.
Summary for patients in
Ann Intern Med. 2008 Nov 4;149(9):I-36.
BACKGROUND: Growth hormone secretion and muscle mass decline from midpuberty throughout life, culminating in sarcopenia, frailty, decreased function, and loss of independence. The decline of growth hormone in the development of sarcopenia is one of many factors, and its etiologic role needs to be demonstrated.
OBJECTIVE: To determine whether MK-677, an oral ghrelin mimetic, increases growth hormone secretion into the young-adult range without serious adverse effects, prevents the decline of fat-free mass, and decreases abdominal visceral fat in healthy older adults.
DESIGN: 2-year, double-blind, randomized, placebo-controlled, modified-crossover clinical trial.
SETTING: General clinical research center study performed at a university hospital.
PARTICIPANTS: 65 healthy adults (men, women receiving hormone replacement therapy, and women not receiving hormone replacement therapy) ranging from 60 to 81 years of age.
INTERVENTION: Oral administration of MK-677, 25 mg, or placebo once daily.
MEASUREMENTS: Growth hormone and insulin-like growth factor I levels. Fat-free mass and abdominal visceral fat were the primary end points after 1 year of treatment. Other end points were body weight, fat mass, insulin sensitivity, lipid and cortisol levels, bone mineral density, limb lean and fat mass, isokinetic strength, function, and quality of life. All end points were assessed at baseline and every 6 months.
RESULTS: Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, -0.5 kg [95% CI, -1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, -1.0 kg [CI, -2.1 to 0.2 kg] vs. 0.8 kg [CI, -0.1 to 1.6 kg], respectively; P = 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001). Body weight increased 0.8 kg (CI, -0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P = 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased. The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, -0.14 mmol/L [CI, -0.27 to -0.01 mmol/L]; -5.4 mg/dL [CI, -10.4 to -0.4 mg/dL]; P = 0.026); no differences between groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 microg/dL [CI, 1.0 to 2.6 microg/dL]) in MK-677 recipients (P = 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.
LIMITATION: Study power (duration and participant number) was insufficient to evaluate functional end points in healthy elderly persons.
CONCLUSION: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.
Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.
AuthorsCopinschi G, et al. Show all Journal
Neuroendocrinology. 1997 Oct;66(4):278-86.
Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.
Here is a post from russianstar at the end of his MK-677 log:
"I finished the cycle 4lbs up, feeling stronger, sleeping better, perfect skin, this is one of my favourite supps.. i will post up a full review shortly, but i will be running this now at 50mg ed next time, it felt like 4iu of gh easily.. was even getting numb fingers."
I look forward to seeing how you find it. Russian star seemed to love it. Didn't workinghard try it for a brief time? It sounds great and very convenient.
I have read that MK-677 causes a dozen HGH pulses over a 24 hour period. I think it would stack perfectly with one vial of cjcDAC per week dosed in a one time inject.
I started my MK-677 last evening at 25mg. This morning I awoke with my left hand totally numb, a definitely side of a high HGH release. My appetite was up upon waking. I ate a very big breakfast.
I took 37.5mg MK-677 this morning and I'm abnormally hungry!!! I can tell this sets off lots of mini HGH pulses throughout the day from the ghrelin release. It's like taking a mini dose of GHRP6 every couple hours. I'm freaking starving!!!
I honestly had my doubts that an oral HGH Secretagogue could work but I was wrong.
I'm in awe of this product! Both of my hands were numb throughout the night at different times. We 're not talking a little tingly. I mean full on numb, dead to the world. I haven't experienced this since I was on a combination of ghrp2/cjc no dac plus 7ius of hgh.
I can see why people say MK-677 is their favorite GH Secretagogue. It's so easy and convenient to use. You just hold it under your tongue for 30 seconds then drink the rest. You only have to take it once a day, although I'm experimenting with twice a day. I just took 37.5mg. You don't have to refrigerate it and you don't need needles so you can take it with you anywhere.
The MK-677 trial run is going well. It's an nice break to not have to take injections. I like to rotate protocols a lot so the body doesn't catch on. This will be a regular part of my hgh peptide rotation, most definitely.
The past couple days I only took MK once a day. Today I'll bump it back up to twice as my hands got more from twice a day. I like the way I'm filling out. I sleep like a baby on MK which is not something I'm usually able to do.
I just took my morning dose of 37.5mg of MK-677. I think this is the perfect gh secretagogue to cycle in between ghrp/GHRH cycles. My guess is when I go back to ghrp2 and cjc no dac that they will work like new just as MK-677 is. The cycling of these combinations will give better results than staying on the same gh peptides. That's my theory because of how well the MK-677 is working.
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.
AuthorsChapman IM, et al. Show all Journal
J Clin Endocrinol Metab. 1996 Dec;81(12):4249-57.
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.
Just got done training arms and calves. The pump was intense! This is the most convenient HGH Secretagogue and inthink as effective as any other. I'm really liking this compound!
Here is a new post from a forum we are on:
"just thought id throw my 2cents in here because i just started with MK-677. the hunger is real and it is intense, and im only at 25mgs. i have literally been hungry almost every hour ive been awake, trying to drink alot of water to make it subside but that really is not working. been eating every 2 hours even while at work. i feel good though. i woke up this morning with a ton of energy and had a very good sleep. i also kind of feel tighter this morning after working out, more so than before using it. my hands were asleep and took a few shakes to wake them up this morning and if one is not moving for a bit while im at my desk, it starts to drift off. i will update more in a few days."
Repeat administration of the GH secretagogue MK-0677 increases and maintains elevated IGF-I levels in beagles.
AuthorsHickey GJ, et al. Show all Journal
J Endocrinol. 1997 Feb;152(2):183-92.
We have reported that MK-0677 is a novel, orally active GH secretagogue that stimulates an immediate and long-lasting increase in serum GH levels in dogs. Significant elevations in IGF-I levels were associated with the increased GH secretion. Cortisol secretion was also increased following MK-0677 administration. In the current study, we determined the effect of repeat oral administration of MK-0677 on GH, IGF-I and cortisol levels; we also investigated if the GH and cortisol responses to MK-0677 are influenced by circulating IGF-I concentrations. Following the initial oral administration of MK-0677, GH secretion (area under the time-response curve (AUC) ng/ml per h) was increased 7.9- to 9.8-fold (1.0 mg/kg), 5.6-fold (0.5 mg/kg) or 3.9-fold (0.25 mg/kg). With repeat MK-0677 administration, the GH response was decreased by 41-77%; GH concentrations remained significantly above control in the 0.5 mg/kg and 1.0 mg/kg groups. Individual beagle GH profiles indicated that the increased GH concentration was associated with an amplified GH pulsatile profile. Serum IGF-I levels were significantly increased over control levels at all dosage levels by 480 min on the first day of MK-0677 administration. With repeated administration, IGF-I levels were increased up to 126% and remained elevated through 14 days, the longest treatment period evaluated. While daily MK-0677 administration appeared to increase IGF-I levels over 24 h, as evidenced by significant increases in the pretreatment IGF-I levels on days 4-14, no such increase was noted with alternate day MK-0677 administration; thus the dosage regimen modulated circulating IGF-I levels. MK-0677 stimulated increases in cortisol secretion (AUC microgram/dl per h) on the first day of treatment. A decreased cortisol response was observed following repeated daily treatment with MK-0677; in contrast, with alternate day treatment, no decrease in cortisol response to MK-0677 occurred. A marked increase in circulating IGF-I concentrations following administration of exogenous GH resulted in a significant decrease in both the GH and cortisol response to MK-0677 compared with control animals. Our findings suggested, therefore, that circulating IGF-I concentrations regulate GH and cortisol response to MK-0677. In summary, chronic oral administration of MK-0677 was associated with significant increases in GH and IGF-I levels that were maintained for the duration of the treatment. The GH profile following MK-0677 administration consisted of episodic increases above control. Compared with day 1, repeated daily treatment with MK-0677 resulted in an attenuated GH response that was associated with an increase in circulating IGF-I levels. The cortisol response was similarly reduced during chronic MK-0677 treatment, suggesting that IGF-I mediated negative feedback on both the GH and cortisol axes. The fact that similar attenuation of the GH and cortisol responses to MK-0677 on day 1 was observed if IGF-I levels were increased by treating animals with exogenous GH suggested that the attenuated response to MK-0677 that occurred during chronic treatment was mediated by increases in IGF-I rather than desensitization to MK-0677. Thus, a regulatory feedback loop apparently prevents hyperstimulation of the GH axis by MK-0677. We conclude that MK-0677 offers the potential of an orally active GH secretagogue that can maintain elevated IGF-I levels when administered chronically.
I think the fact that MK-677 creates HGH pulses for 24 hours straight is the reason I'm getting all the same side effects I get when I take synthetic HGH as in the numb hands, deep sleep, lethargia, hunger, full muscles, etc. This feels to me as the closest HGH Secretagogue to real synthetic HGH coming from a GHRP, whereas cjcDAC is the closest HGH Secretagogue to synthetic HGH coming from a GHRH.
Post from a Superior customer into thread at promuscle whomiscstackung our GW and MK:
"Been running for about a week. The stamina and endurance from GW is noticeable right away. Been flying through workouts, taking shorter breaks. Too early to tell about fat loss, but i do feel tighter,but thats prob due to the combo of both. Getting very good pumps in the gym, id compare the pumps to a really good anaavar pump like pharmaceutical grade. I got one so bad my right arm locked up while taking a drink from my water. Sleep has been great, and the intense hunger has kind of curbed itself. Still hungry alot but not dying every hour like i was. I did notice my skin is alot better. I just came off a test/tren/mast and anavar cycle and my skin gets very oily during PCT. within 2 days my skin was back to normal, as if i was off cycle."
Post from my thread at promuscle...
"got it today. that was crazy quick. took my first dose this afternoon. got a big hunger reaction. bam. i was eating like crazy."
I've been taking my pramipexole and Mk677 together post workout. This allows me to eat like an animal every hour or two and sleep well by the time I'm ready to go to bed. The two together make me real hungry which is perfect for post workout recovery. I find 4pm optimal to dose both so I can sleep by 11pm. I'm up to .5mg pramipexole and sticking with 25mg MK677.
Also, I found it only takes 2-3 days off from MK to make it work like new again in terms of a ferocious hunger.
I added 2mg cjcDAC once a week to my MK677. I notice I get more hand numbness when I sleep. I believe there is good synergy between the two since one is a GHRP and the other is a GHRH.
Ever since a Superior customer confirmed it makes all the difference taking MK677 sublingually I last night left it in my mouth for 5 minutes holding it under my tongue for a few then swishing it around like mouth wash. I got very numb hands last night.
MK-677 is the strongest GH booster I have ever taken. The tiredness is severe though!
I believe I have just found the best way to use MK677.
I started thinking about it last night that no matter how much I put under my tongue, only so much gets pulled into my blood stream sublingually and the rest I have to swallow. Sublingual absorption is approximately 90% pulled along with the grain alcohol. The rest gets swallowed with only a 30% absorption rate. So, why not take 5mg every few hours to get the full 90% absorption into the blood stream?
I tested this last night and took a small dose of around 5mg which is very little and held it under my tongue for around two minutes while I made a protein/oat drink. By the time I finished making my drink most of the MK677 had fully absorbed sublingually. In then chugged my drink and went to bed. I repeated this routine each time I woke up to use the bathroom. What happened was my dreams were like nothing you could imagine, so life-like and real it was scary.
The first post MK677 dose I had a horrible nightmare where I was being tortured by a force not of this world. This is the creepy part. I shit you not. I could literally feel the physical pain of being tortured and it lasted what felt like 10 full minutes. It was terrible!
I woke up 4 hours later and did my next sublingual 5mg MK677 dose and held it under my tongue while I made my protein/oat drink, then chugged it. The same thing happened. My dreams were angry dreams where I was screaming and telling at the top of my lungs at people out of rage and frustration. The dreams were so incredibly real!!! I woke up 4 hours later and repeated the procedure again.
Another big note was the level of hand numbness was extreme. With my first two dosings I'd say I actually took more than 5mg MK677 but with a little thought I realized that only approximately 5mg was able to get pulled in sublingually with the grain alcohol.
I believe this method will give the greatest HGH output. 5mg every 4 hours or so and let all of it sit under your tongue until you no longer taste the grain alcohol or feel it's burn.
I am only using MK677 currently for HGH output. I ran out of huperzine A and couldn't afford cjcDAC, pramipexole facks me up too hard the next day. My hands were so numb last night that I'm convinced with this method MK677 is all I need, the poor man's HGH.
I took my 5mg 4 times in the last 9 hours and had a protein drink with each. I took NyQuil before bed as well. My dreams were crazy!!! I dreamed I was murdered but remained here as a ghost. I could fly and only crazy homeless people could see me. Hahahaha
The experience of being murdered was in a car and I could feel the sensation of incredibly fast speed as the car shot a hundred miles an hour over an embankment off a cliff.
I'm consistently healing very fast in between workouts. MK677 is currently my only hgh Secretagogue.
I kicked my MK dose up to 50mg split dosing just for the hell of it. I finally got some huperzine A and and dosing it 2-3 times a day at 200mcg, and I'm taking .2mg pramipexole before bed and .1mg more in the middle of the night when I go to the bathroom. The somatostatin inhibition from huperzine and prami really kicked up the level of hand numbness a notch.
I am near the end of my MK-677 bottle. I probably have about 2 doses left. I went through 2 bottles and loved it. Looking forward to trying it again in the near future
I'm absolutely amazed at the changes in my physique after 5 days of MK-677 and cjcDAC. I have lost control and had a huge cheat meal every night for 3 nights but my abs look tighter. I'm going to try not to cheat for a few days. I look much bigger and tighter. Weight up from 223Lbs to 228Lbs. There is no subcutaneous water retention as of yet.
Last night I dosed 50mg MK-677 before bed.
OMG!!! It hit so much harder than 25mg! It knocked me on my ass!
Real vivid dreams. I'm a little groggy this morning. At that I dose I needed a couple more hours sleep. I definitely like night time dosing best!
I think I found my perfect MK-677 protocol finally. 50mg was too powerful and left me groggy.
Last night I took 37.5mg, which is a full dropper worth, with 10mg melatonin. I had the best sleep I've had in ages, and I'm
not groggy today.
The pumps have been so incredible off MK-677 with tadalafil. I'm up 6Lbs in 9 days and haven't had a cheat meal in 6 days.
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