Tuesday, November 11, 2008

MK-677, Oral Ghrelin Mimetic, Stimulates Youthful Pulsatile HGH Secretion in Elderly

Via NextBigFuture, this Annals of Internal Medicine article looks at the effect of an oral ghrelin mimetic on secretion of HGH, and various physical measurements such as muscle mass, visceral fat, etc.
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.

Previous trials in which growth hormone was administered to elderly persons were small, poorly controlled, or too short (8); in addition, growth hormone replacement does not restore pulsatile growth hormone secretion. MK-677, the first orally active ghrelin mimetic (a growth hormone secretagogue and growth hormone secretagogue–receptor agonist), increases pulsatile growth hormone secretion in older adults to levels observed in young adults (9, 10). Our primary objectives were to determine whether 25 mg of oral MK-677 daily would increase growth hormone and insulin-like growth factor I (IGF-I) levels in healthy older adults, prevent the decline in fat-free mass, and decrease abdominal visceral fat, with acceptable tolerability.

...Frailty is one of the scourges of elderly persons, and as researchers are beginning to learn about its causes, they are asking whether growth hormone deficiency is one of them. A systematic review (8) concluded that the risks of exogenous growth hormone outweigh the benefits and that it is not the long-sought solution to frailty. The promise of MK-677 is that it seems to restore endogenous growth hormone levels in a physiologic secretory pattern, unlike the single high-amplitude pulse observed after exogenous growth hormone administration. We believe that our study sets the stage for an adequately powered clinical trial of sufficient duration in a population vulnerable to frailty. _AnnalsIntMed
The effects of the more physiologic pattern of HGH secretion seen in MK-677 recipients vs. standard HGH replacement protocols, suggests that more indirect route of using an oral ghrelin mimetic may provide better long-term results.

The most significant adverse effect was an increase in appetite, which in many elderly might be seen as more of a positive miracle than an adverse effect. I encourage anyone interested to go to the article itself and read it in full. The complexity of homeostasis in the human organism should discourage simplistic and cavalier interventions for purposes of senescence mitigation. The study quoted above is a good example of a thoughtful and fairly comprehensive look at a measured intervention. The findings should be confirmed and integrated into the leading theories of senescence mitigation and reversal.



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