Why pulsatile secretion matters for interpreting secretagogue claims — a second dataset

This follows post #12 rather than contradicting it.

Source for the pulsatile secretion figure, since it was asked for. It is in the discussion rather than the abstract, which is why the version circulating is stronger than the paper is.

Reading the surrounding paragraph is worth the two minutes. The authors are more careful than their summarisers.

I disagree with the framing of pulsatile secretion above, and I think it is a substantive disagreement rather than a terminological one. Setting out why, so it can be checked.

The reasoning depends on an assumption that is doing a lot of work and is never stated. If the assumption holds, the conclusion follows. I do not think it holds generally.

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.

Anyone with a larger sample, please post it.

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.

This is where my knowledge stops and I would rather mark the edge than blur it.

That is clearer than the version I had in my head. Thank you.

The question underneath pulsatile secretion is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.

Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.

Post #20 put the caveat in the right place and I want to underline it.

On analysis: these are short peptides and generally straightforward chromatographically, which means a poor purity result is more likely to reflect the synthesis than the method.

Posted with less confidence than the sentence structure implies.

Summarising the pulsatile secretion thread so far, since it is long and the answer is buried: the first reply has the method, the fourth has the correction to it, and the rest is people agreeing at length.

One more thing on pulsatile secretion that took me far too long to see: the two figures people quote are not measuring the same quantity. Once you notice that, the apparent contradiction disappears.

The arithmetic in post #23 is right; the assumption feeding it is the part to check.

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.

The short version is the first sentence; the rest is why.

The pulsatile character of endogenous growth hormone release is why a secretagogue and exogenous growth hormone are not interchangeable, and why a single measured level tells you very little about either.

This is the sort of thing the wiki should carry and currently does not.

Counterpoint on pulsatile secretion, offered without confidence: the same observation is consistent with a much duller explanation, and nobody has ruled the dull one out.

Second this, and I would have said it less carefully.

Adding the measurement that post #26 says would settle it.

Injection-site reactions are reported more often in this family than for the incretins. Whether that is the compounds or the preparations they are typically supplied in is not established.

Reading it back, the second half matters more than the first.

I read the earlier replies on pulsatile secretion twice before writing this, because I had assumed the opposite and wanted to be sure I was disagreeing with what was said rather than what I expected.

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.