The comparison register

Placebo responses

The GHK-containing scalp mixture improved hair counts more than placebo; counts increased in the placebo group too. The STEP 1 semaglutide trial also recorded an average change in its placebo group, here a loss of weight.

Neither observation establishes that an inactive ingredient caused the change. A comparison group can capture other influences on a result. The controlled difference persuades me. Simply crediting treatment with every later change would claim too much.

The scalp trial has a further attribution problem because the active treatment combines GHK with another ingredient. Placebo helps establish that the mixture had an effect; separating the active ingredients would require more groups.

A competing medicine

In SURMOUNT-5, semaglutide met tirzepatide within the same weight-loss trial. Tirzepatide produced the greater mean loss at 72 weeks. That is a particularly useful comparison when the question concerns the two medicines’ weight effects.

It leaves the heart and kidney questions with their own evidence. SELECT and FLOW compared semaglutide with placebo and studied different clinical populations. A universal winner across these outcomes would need quite different comparisons.

Removing a mechanism

The NAD+ experiments offer a different sort of company. Mice lacking CD38 were protected against an age-related fall in NAD+. In the mouse heart-failure model, reducing HMGCS2 prevented NAD+ repletion from rescuing cardiac function.

One intervention removed an enzyme that consumes NAD+; the other reduced a proposed link between NAD+ and a heart benefit. These manipulations help explain why something happens inside the experimental model.

I value that capacity to trouble an explanation. The most interesting experiment may be the one that makes the hoped-for effect disappear. Its clinical relevance still requires treatment studies in people.

The human observation

The MOTS-c dialysis cohort compared people’s existing blood concentrations with later outcomes. Its participants received no MOTS-c intervention. Higher circulating MOTS-c was associated with the combined mortality and cardiovascular outcome, and its inclusion improved a risk model.

My question there is what the concentration signifies in illness. A treatment trial would ask what happens when investigators deliberately give MOTS-c. Changing the verb changes the experiment.

Comparisons still missing

• A component-by-component test of the GHK scalp mixture would help assign the observed hair-count gain.
• Human MOTS-c treatment trials would have to measure benefit and safety directly, beyond mouse performance and human blood associations.
• NAD+ precursor research needs clearer connections between blood increases, tissue changes and useful human outcomes, as the clinical review describes.

These gaps let me ask about ingredients, tissue and function, rather than merely attaching the word “early” to everything.