Orally Active Growth Hormone Release?


mk-677-Growth-Hormone-GH-ReleaseStudies are being conducted right now on a research chemical that is designed to increase Growth Hormone and IGF-1 levels significantly. We already have access to GRF (Modified GRF 1-29) and several effective GHRP’s (Ipamorelin, GHRP-2, GHRP-6) which, when combined, can increase GH levels substantially. What makes this new research chemical unique?

Well for starters, it’s orally bioavailable. For many people who want to avoid injections twice or three times per day (the recommended amount for adequate GH release), an orally active version is a godsend. What I like even more about it though, is that according to research, it increases GH and IGF-1 without a subsequent increase in Prolactin or Cortisol. GRF and GHRP-2,-6, all increase Prolactin and Cortisol, to a pretty significant degree. Ipamorelin stands alone as the only GHRP that has almost no effect on these other two hormones. So the fact that MK-677, also known as Ibutamoren, increases growth hormone without the negative release of Prolactin and Cortisol sounds incredibly promising.

I am in no way suggesting anyone use this stuff. I mean it. It is a research chem available on several sites that specialize in the sale of research chems, in particular SARMs products (selective androgen receptor modulators). While some of these research chems have had enough research backing their safety, and are actually used in medical settings (sermorelin for instance), drugs like Ibutamoren are still way too early in their infancy to just start drinking this stuff.

Another interesting point, and this may be challenged, is that research is showing Ibutamoren increases muscle mass and bone density, while also decreasing fat mass. While we know that GH itself is very useful for fat loss, it has always fallen short in studies researching Growth Hormone’s effect on muscle protein synthesis.

Mk-677, and Orally Active Growth Hormone Secretagogue

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 μg/L after single dose (day 1 of treatment) and 22.6 ± 9.3 μg/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 μg/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.

The only reason I question the results showing muscle growth (although I do believe GH can be anti-catabolic, I’ve never seen any solid evidence that it is, in and of itself anabolic) is that the research being done is no doubt being funded by a company whose financial interest lies in showing these results. The numbers above speak for themselves, but I’m still not convinced that there is some real bias taking place here.

Because Ibutamoren is still a Ghrelin mimetic (meaning it has a GHRP type effect) it will be very useful to also use GRF, or CJC-1295 w/o DAC (needed multiple times per day) or CJC-1295 w/DAC (lasts several days rather than hours so less frequent injections). So far, I only see anecdotal bro-science type feedback on this drug. I will keep my ear to the rail and see if I learn something new about this unique GH promoter.