GHRH analogues: lipid and glucose findings
A proposed benefit for the mind would still have to answer for its effects elsewhere. The GHRH studies offer some specific entries in that account.
Blood lipids during Nle27-GHRH treatment
An experiment in age-advanced men and women used the analogue [Nle27]GHRH-(1-29)-NH2 for 16 weeks. IGF-I and IGFBP-3 rose. Body weight and blood pressure stayed unchanged, as did fasting insulin and glucose. The reported adverse effect was transient hyperlipidemia, a rise in blood lipids, which resolved by the end of the study.
The resolution deserves mention alongside the change. Why did the lipids rise, and would a larger or longer study tell the same story? They affect how persuasive the result seems. The reported change resolved, and these follow-up questions supply no evidence of a lasting injury.
The unchanged body weight also deserves a line of its own. The hormone response in this experiment came with a weight measurement that stayed put. Attaching weight loss to the cognitive argument would misrepresent this unchanged measurement.
PEG-conjugated GHRH
A safety and tolerability study of PEG-conjugated GHRH included healthy young men and elderly subjects. GH and IGF-I increased. Reactions at injection sites occurred more frequently than with placebo, though they were mild and transient; no antibodies to GHRH were observed.
Some impairment of glucose tolerance appeared in the elderly subjects with repeated exposure. This was a chemically different GHRH preparation from the one used in the lipid study, and both differ from tesamorelin in the cognition trial.
These reports give the metabolic discussion a subject more concrete than general reassurance. A separate side-effect account for each preparation seems essential to me.
Tesamorelin trial tolerability
The tesamorelin cognition trial described adverse events as mild. That is the tolerability description belonging to that trial. The glucose-tolerance observation and the temporary lipid change belong to the other preparations and settings described above.
A future claim about sustained cognitive benefit deserves an equally accessible account of its metabolic consequences. My enthusiasm would depend on both. A broad anti-aging endorsement asks for much more than an interesting mental-performance result and a brief tolerability description.
The secretagogue editorial
An editorial in Annals of Internal Medicine questioned whether growth hormone secretagogues were justified for preventing or treating aging. A secretagogue prompts secretion; here the intended secretion is growth hormone.
I take that objection seriously without asking an editorial to decide the later experiments in advance. The question is the proposed use: a particular cognitive investigation can be worth doing while a general program of reversing age-related change remains unpersuasive. The human trial gives the narrower proposition something to discuss.