I've discovered that MK-677 works as a capsule , doesn't need refrigeration, dramatically increases deep sleep and effectively restores GH (growth hormone) to youthful levels, effectively treating crippling sleep disorders.
MK-677 Should only be used for 1 week cycles , with 5 weeks off.
MK-677 if used monthly will shut down your HPA Axis with such serious consequences that your GH levels will plummett to the abyss, and your pituitary simply stops secreting.
Besides cold therapy for sleep, Mk-677 which was also studied for 1 year in the elderly population... The 1 year clinical trial is free online:
"Daily MK-677 significantly increased GH and IGF-I levels to those of healthy young adults without serious adverse effects."
GH = Healing Injuries Healing Bones, Tendons and Ligaments Extremely restful restorative sleep Protecting muscle tissue
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Neuroendocrinology. 1997 Oct;66(4):278-86.
Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.
Copinschi G1, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, Mendel CM, De Lepeleire I, Bolognese JA, Van Cauter E.
Author information
- 1Center for the Study of Biological Rhythms (CERB) and Laboratory of Experimental Medicine, Free University of Brussels, Belgium.
Abstract
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.
J Clin Endocrinol Metab. 1996 Dec;81(12):4249-57.
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.
Chapman IM1, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ,Thorner MO.
Author information
- 1Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
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.
Following treatment with 50 mg MK-677, IGF-I concentrations increased 79 ± 9% (84 ± 3 to 150 ± 6 μg/L, P ≤ 0.05 vs. baseline) and 24-h mean GH concentrations increased 82 ± 29% (0.21 ± 0.02 to 0.39 ± 0.04μ g/L, P ≤ 0.05 vs. baseline), respectively - See more at: http://press.endocrine.org/
Response to treatment
Oral treatment with both 10 mg and 50 mg/day MK-677 was associated with statistically significant increases in circulating concentrations of GH, IGF-I, and IGFBP-3, whereas placebo treatment was without a significant effect on these parameters (Table 2).
GH
Adverse experiences
MK-677 treatment was generally well tolerated and no symptoms developed that were definitely attributed to study drug. There were no serious adverse events during this study, and no subjects were discontinued or had treatment interrupted because of an adverse experience.
- See more at: http://press.endocrine.org/
The increase in GH concentrations produced by MK-677 treatment was because of an increase in GH pulse, amplitude, and interpeak valley and nadir GH concentrations and not because of increased pulse frequency. - See more at: http://press.endocrine.org/
This enhancement of GH pulsatility occurs whether these compounds are administered continuously as intravenous infusions or as daily administrations of the long-acting compound MK-677. This suggests that these compounds amplify the normal signals responsible for episodic GH release. This could occur via relief of an inhibitory effect, such as that of somatostatin, enhancement of a stimulatory effect, such as that of GHRH, or a combination of both.
The stimulatory effect of MK-677 on mean GH concentrations in the 8 h after drug administration declined between the first and fourth day of drug administration, although the fourth day value was still significantly greater than baseline. This decline may indicate desensitization to the GH stimulatory effects of the drug and foreshadow an eventual loss of stimulatory effect. Alternately, and probably more likely, it may result from negative feedback effects of IGF-I on GH secretion.
- See more at: http://press.endocrine.org/
Favorable changes in body composition because of MK-677-induced increases in GH secretion could conceivably counteract any unfavorable effects on insulin resistance. GH therapy in GH-deficient subjects has been reported to increase insulin resistance at 6 weeks, but have a diminished effect at 26 weeks when significant decreases of body fat have occurred (42). - See more at: http://press.endocrine.org/
Notably, daily oral administration of MK-677 increases plasma GH concentration in healthy elderly subjects and also increases their plasma IGF-I concentration to the normal range of young adults (Chapman et al. 1996).
Among these GH secretagogues (GHSs), MK-677 has been reported to show good oral bioavailability. In addition, chemically synthesized GHSs including GHRP-6 and MK-677 have been reported to show highly potent GHreleasing activity in several species including humans (Walker et al. 1990, Bowers et al. 1992, Hartman et al. 1992, Chapman et al. 1996).
Two-Month Treatment of Obese Subjects with the Oral Growth Hormone (GH) Secretagogue MK-677 Increases GH Secretion, Fat-Free Mass, and Energy Expenditure
J. Svensson, L. Lönn, J.-O. Jansson, G. Murphy, D. Wyss, D. Krupa, K. Cerchio, W. Polvino, B. Gertz, I. Boseaus, L. Sjöström, and B.-Å. Bengtsson
Address all correspondence and requests for reprints to: Dr. Johan Svensson, Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
Received: June 19, 1997
Accepted: October 14, 1997
First Published Online: July 01, 2013
- See more at: http://press.endocrine.org/
ABSTRACT
Obesity is associated with blunted GH secretion, unfavorable body composition, and increased cardiovascular mortality. The objective of this study was to investigate the effects of oral treatment with the GH secretagogue MK-677 on GH secretion and body composition in otherwise healthy obese males. The study was randomized, double blind, parallel, and placebo controlled. Twenty-four obese males, aged 18–50 yr, with body mass indexes greater than 30 kg/m2 and waist/hip ratios greater than 0.95, were treated with MK-677 25 mg (n = 12) or placebo (n = 12) daily for 8 weeks.
Serum insulin-like growth factor I (IGF-I) increased approximately 40% with MK-677 treatment (P < 0.001 vs. placebo). Serum IGF-binding protein-3 was also significantly increased (P ≤ 0.001 vs. placebo). GH and PRL (peak and area under the curve values) were significantly increased after the initial dose of MK-677. Significant increases, with the exception of peak PRL, persisted at 2 and 8 weeks of treatment. The increases in GH and PRL after the initial dose were significantly greater than the increase seen after multiple doses. Serum and urinary concentrations of cortisol were not increased at 2 and 8 weeks (P = NS, vs. placebo). Fat-free mass increased significantly in the MK-677 treatment group when determined with dual energy x-ray absorptiometry (P < 0.01) or using a four-compartment model (P < 0.05). Total and visceral fat were not significantly changed with active therapy. The basal metabolic rate was significantly increased at 2 weeks of MK-677 treatment (P = 0.01) but not at 8 weeks (P = 0.1). Fasting concentrations of glucose and insulin were unchanged, whereas an oral glucose tolerance test showed impairment of glucose homeostasis at 2 and 8 weeks.
We conclude that 2-month treatment with MK-677 in healthy obese males caused a sustained increase in serum levels of GH, IGF-I, and IGF-binding protein-3. The effects on cortisol secretion were transient. Changes in body composition and energy expenditure were of an anabolic nature, with a sustained increase in fat-free mass and a transient increase in basal metabolic rate. Further studies are needed to evaluate whether a higher dose of MK-677 or a more prolonged treatment period can promote a reduction in body fat.
J Clin Endocrinol Metab. 1996 Aug;81(8):2776-82.
Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.
Copinschi G1, Van Onderbergen A, L'Hermite-Balériaux M, Mendel CM, Caufriez A, Leproult R, Bolognese JA, De Smet M, Thorner MO, Van Cauter E.
Author information
- 1Center for the Study of Biological Rhythms, Université Libre de Bruxelles, Belgium.
A central enigma in neuroendocrine pathophysiology is the virtually uniform, but mechanistically incompletely explicable, attenuation of secretory and trophic activity of the growth hormone (GH)—insulin-like growth factor type I (IGF-I) axis in healthy aging in mammalian species, including the primate and human. Indeed, in humans, the calculated daily GH secretion rate falls approximately 50% every 7 years beginning at age 18 to 21, but this diminution in GH secretion is approximately twofold less rapid in premenopausal women. In contrast, the magnitude of relative GH deficiency appears to be similar in individuals of older (e.g., postmenopausal) age of either gender. Interpreting the mechanisms that underlie such marked attenuation of secretory activity of the GH-IGF-I axis is confounded by endocrinemetabolic covariates that accompany healthy aging, such as an accumulation of (visceral) adiposity, a decline in physical fitness, a reduction in sex steroids, disruption of slow-wave sleep, and concurrent illness and medications. Available clinical investigations point to a partial endogenous GHRH deficiency state, in this so-called somatopause. An important additional age-related fall in brain cholinergic activity (which regulates somatostatin secretion) is likely, thus arguing for combined hypothalamic somatostatin excess and GHRH, GHRP, or both deficiency. This article also evaluates the novel hypothesis that the GH impoverishment of aging is marked by disrupted network function of the GH-IGF-I feedback axis. Given this background, available and new technologies applied in patient-oriented investigations will likely unravel further the presumptively multiple mechanisms that subserve the hyposomatotropism of healthy aging, and begin to address the relative risks and benefits of restoring secretory activity of the aging GH-IGF-I axis.
MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism
M. G. Murphy, L. M. Plunkett, B. J. Gertz, W. He, J. Wittreich, W. M. Polvino 2 , and D. R. Clemmons
Address all correspondence and requests for reprints to: M. Gail Murphy, Merck Research Laboratories, Building 10, Sentry Parkway, Bluebell, Pennsylvania 19422.
Received: May 14, 1997
Accepted: October 28, 1997
First Published Online: July 01, 2013
Abstract
The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19–49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively. MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43–44% after 2–8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-I and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.
Abstract
To assess the effects of prolonged administration of a novel analog of GH-releasing peptide (MK-677), nine healthy young men participated in a randomized, double blind, three-period cross-over comparison of orally administered placebo and 5- and 25-mg doses of MK-677. Each period involved bedtime administration of the drug for 7 consecutive days. At the end of each period, plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured at 0745 h, and 24-h profiles of plasma GH and cortisol were obtained at 15-min intervals together with the 24-h urinary excretion of free cortisol. Profiles of plasma free cortisol were calculated at hourly intervals. The amounts of GH secreted were similar in all three conditions, but GH pulse frequency was increased with both dosages of the drug, primarily because of an increase in the number of low amplitude pulses. Plasma IGF-I levels were increased in a dose-dependent manner, whereas IGFBP-3 levels were increased only with the highest dosage. There was a positive relationship between GH pulse frequency and IGF-I increase. Except for an advance in the nocturnal nadir and in the morning elevation, MK-677 had no effect on cortisol profiles. In particular, 24-h mean levels of plasma total and free cortisol and urinary excretion of free cortisol were similar under all conditions. The present data suggest that the use of MK-677 for the treatment of relative somatotropic deficiency, particularly in older adults compromised by such deficiency, deserves further investigation.
Studies have found that in general, the optimal temperature for sleep is quite cool, around 60 to 68 degrees Fahrenheit. For some, temperatures that fall too far below or above this range can lead to restlessness.
Temperatures in this range, it seems, help facilitate the decrease in core body temperature that in turn initiates sleepiness. A growing number of studies are finding that temperature regulation plays a role in many cases of chronic insomnia. Researchers have shown, for example, that insomniacs tend to have a warmer core body temperature than normal sleepers just before bed, which leads to heightened arousal and a struggle to fall asleep as the body tries to reset its internal thermostat.
. Studies show that for troubled sleepers, a cool room and a hot-water bottle placed at the feet, which rapidly dilates blood vessels, can push the internal thermostat to a better setting.
THE BOTTOM LINE insomniacs tend to have a warmer core body temperature than normal sleepers just before bed, which leads to heightened arousal.
