Thanks, Mike!
Yes, firstly - one of my favorite quotes is a Zen koan: "If you meet a Buddha in the road, kill him" which can be interpreted to mean that if someone says they're you're end all be all "guru" that's the last guy to trust. (And that includes me, of course! LOL) Ultimately, we each make the call to trust someone. (Thanks for trusting me, though, CG!!!)
Also, I address MK-677 on my podcast (with Scott McNally) called Muscle Minds, not Gear'd up. (I was on that one like 3yr ago I think...)
And yes, as Mike mentioned, I was looking at the data (and I posted these in one of my last posts in that other thread) not someone's blood panels, and there is a reduction in the AUC of GH from first dose (25mg) to that two weeks later, but the elevation in GH release is NOT eliminated.
In one study of obese subjections, after a couple weeks week GH AUC is about 25% of the first dose and seems to stay that way up to the 8 week out mark with daily dosing (25mg). This study also shows about a 1.5 fold elevation in IGF-1 that persists for the full 8 weeks.
1. Svensson J, Lonn L, Jansson JO, et al. 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 Clin Endocrinol Metab. 1998;83(2):362-369.
There is another 1 week study - daily dosing - showing that at the end of one week, there is no difference between placebo and either a low (5mg) or high (25mg) GH AUC, suggesting no elevation of GH on average, although the # of GH peaks is increased with both doses. This one is a nice study b/c the put up data from individuals and you can see the variability. But there IS an elevation of IGF-1 here - about 25-40% just eyeballing the bar graph (Fig 3).
1. Copinschi G, Van Onderbergen A, L'Hermite-Baleriaux M, et al. 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. J Clin Endocrinol Metab. 1996;81(8):2776-2782.
The longest study I know of is with older folks suggests that even at the 1 year mark, GH 24hr AUC is elevated 1.5fold above placebo and IGF-1 is elevated 1.8 fold with 25mg / day.
1. Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized, Controlled Trial. Ann Intern Med. 2008;149(9):601-611.
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So there's some variability in the GH response, it seems to diminish rather quickly after the first dose, with one study showing that it's eliminated at one week (compared to placebo) but others showing substantial increases above placebo (Obese subjects) and another showing more modest increases (older folks) that persist for months - years.
It seems to consistently increase IGF-1, and effect that persists for many months.
SO - THE QUESTION I WAS ASKED to respond to on the podcast was loss of responsiveness to the MK-677, so that was the focus there. It's very powerful first response and seems to fade - RELATIVE to that - quite a bit (25% of initial value for 24hr AUC or even to nothing in one study) in a matter of days.
So the guy who asked the original Q might have simply been one of those poor responders to MK-677, which is something that is in the study showing no difference in placebo vs. both MK-677 doses on average also showed with individual data points, and something that Mike A. also mentioned in that other thread.
A better question is whether something like EOD dosing could retain sensitivity and thus literally get more GH bang for the MK-677 buck. I would imagine if GH AUC were elevated the same with and EOD protocol vs. daily dosing, that IGF-1 levels would be similar.
Also in the low vs. high dosing study, 5mg elevated IGF-1 about 25% vs. 40% with 25mg... So, there may be more papers out there to help delineate a dose response for a single dose, but one could speculate that using more than what approaches a "saturation" dose or whatever minimal dose created the maximal elevation in GH AUC would only reduce the GH release from repeated dosing (by causing greater down regulation)...
So, those guys who might be using like 10-12.5mg EOD or perhaps only several days / week might be on to something.
-S