This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Adding the measurement that post #30 says would settle it.
Effects reported at the level of appetite are the most consistently described and the most mechanistically direct for the ghrelin-receptor compounds, which is not what most people are taking them for.
The confident version of this sentence would be wrong, so here is the hedged one.
The reason pulsatile secretion is hard to answer is that the obvious measurement and the relevant quantity are not the same thing, and substituting one for the other is silent.
Two sentences on pulsatile secretion and then I will stop, because the rest is speculation and the thread is better without mine.
What is documented is narrow. What is inferred from it is broad. The gap between them is where every argument here lives.
Where I part company with post #32, and it is a narrow parting.
Growth hormone secretagogues act on the ghrelin receptor or on the growth hormone releasing hormone receptor rather than supplying growth hormone, which is the distinction that matters for anyone reading the literature.
Worth reading the earlier posts in this thread before acting on mine.
I would be cautious about generalising from the pulsatile secretion example above. It is a good example. It is one example.
No disagreement from me. Posting only so the question does not look ignored.
Building on post #34 rather than restating it.
Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.
A single observation, in a thread that deserves better than single observations.
Post #37 put the caveat in the right place and I want to underline it.
GHRH analogues versus ghrelin mimetics are often conflated but they are different mechanisms. GHRH analogues (like CJC-1295) cause the pituitary to release growth hormone. Ghrelin mimetics (like GHRPs) act on the ghrelin receptor directly. The effect on growth hormone secretion is similar but the mechanisms are distinct.
I would put the burden of proof on the interesting explanation, not the dull one.
Pulsatile secretion was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
Post #37 and I disagree about the size of the effect, not about the direction.
I think the pulsatile secretion question is answerable and has not been answered, which is a more optimistic position than most of this thread.
Saving this. It is the version I will quote when the question comes round again.
A mass result for a short peptide is more discriminating than for a long one, because a single residue difference is a larger proportion of the total. That makes identity confirmation genuinely useful here.
Take it as a starting point and not as a specification.
The strongest argument against my own position on pulsatile secretion, stated as well as I can state it, since nobody else has yet.
Distinguishing three things in the pulsatile secretion discussion that keep getting used interchangeably: the observation, the proposed mechanism, and the recommendation that gets attached to both.
Storage: these are lyophilised short peptides and are generally reasonably stable dry and considerably less so in solution. Reconstituting only what will be used within the period the supplier's own data covers is the conservative approach.
Written in the hope of being told what I have missed.
Post #46 is right about the mechanism and I think understates the practical bit.
Evidence quality in the secretagogue literature is honestly weaker than in the incretin literature. Large randomised controlled trials are rare. Most evidence is mechanistic or from small studies. This is why this subcategory has higher sourcing standards than most.
Ipamorelin selectivity claims originate in preclinical characterisation and are reasonably well supported for what they claim: less effect on cortisol and prolactin than earlier GHRPs. Whether that translates to something clinically meaningful is a different question from whether the selectivity is real.
Correct me on the arithmetic if it is wrong; I would rather know.
Post #49 is the version of this I will quote in future. One addition.
Reading a rodent study on a secretagogue without over-extrapolating: rodent studies can show a mechanism is plausible. They cannot show magnitude of effect in humans or safety profile in humans. That gap is larger for secretagogues than for incretin agonists because the human evidence is thinner.
I would call that likely rather than established.
Picking up post #48: that is the part I would want checked first.
The reason pulsatile secretion keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.
Taking pulsatile secretion seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
What a well-designed human trial of a secretagogue would look like: randomised, placebo-controlled, adequate sample size, IGF-1 as primary outcome, muscle and strength as secondary outcomes, adequate follow-up duration. Very few secretagogue trials meet that description.
One of those cases where knowing the mechanism does not help the decision.
Useful. I had the fact and not the reason, which turns out to be the important half.
Why this subcategory is stricter about sourcing than most: the evidence base is weaker and that is precisely why documentation quality matters more. A supplier page that clearly identifies the compound and the purity is more valuable for secretagogues than for incretin agonists where the evidence base is stronger.
Ipamorelin is usually described as selective in that it produces less of an effect on cortisol and prolactin than earlier compounds in the family. Selective is a relative claim and the comparison group matters.
It took me longer than it should have to see that.
Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.
If anyone has run this properly I would rather read that than my own guess.
GHRH analogues versus ghrelin mimetics are often conflated but they are different mechanisms. GHRH analogues (like CJC-1295) cause the pituitary to release growth hormone. Ghrelin mimetics (like GHRPs) act on the ghrelin receptor directly. The effect on growth hormone secretion is similar but the mechanisms are distinct.
Not a strong opinion, just a consistent one.