NAD+: what the human evidence actually shows

What the evidence actually shows

The honest summary: the biology is real and the clinical evidence is thin. NAD+ levels do decline with age, and that decline is genuinely implicated in mitochondrial dysfunction — this is well-established cell biology. What has not been established is that supplementing NAD+ or its precursors in humans reverses ageing, restores energy, or improves cognition. Human trials of NAD+ precursors have been small and short, have generally shown that blood NAD+ levels can be raised, and have largely failed to demonstrate the downstream clinical benefits that the marketing promises. Raising a biomarker is not the same as improving an outcome. Most of the striking results come from mice, and mouse longevity findings have a long history of not translating to humans.

Absolute versus relative: reading the number correctly

Trial results are usually reported as relative figures, because relative figures are larger and therefore more persuasive. A "20% reduction in cardiovascular events" sounds transformative. The absolute reduction in SELECT was from 8.0% to 6.5% — about 1.5 percentage points over roughly three years. Both statements describe the same result honestly; only one of them tells you what to expect for yourself.

The same applies to weight-loss figures. A mean reduction of 20.9% is a mean. Individual results in these trials ranged from substantial loss to none at all, and a mean tells you nothing about where you personally would land. Anyone quoting a trial average as a promise is misusing it.

Funding and conflicts of interest

Every pivotal trial in this field was funded by the company that manufactures the drug it tested. That is normal in pharmaceutical research and it does not make the results false — these are large, well-conducted, peer-reviewed studies. It does mean the funding belongs in the citation every time, particularly for head-to-head trials where the funder makes the winning drug. SURMOUNT-5 was funded by Eli Lilly and found Lilly's drug superior. The result is plausible and consistent with the separate trial programmes; the disclosure still belongs beside it.

Where this sits against the other evidence

No single trial should be read alone. The strength of the GLP-1 evidence base is that multiple independent trial programmes — SURMOUNT for tirzepatide, STEP for semaglutide, SCALE for liraglutide, SELECT for cardiovascular outcomes — point in a consistent direction across tens of thousands of participants. That consistency is what makes the class credible.

What that consistency does not do is extend to products the trials never tested. Every one of those programmes studied an FDA-approved subcutaneous injection. None studied a compounded preparation, a microdose regimen, or an orally disintegrating tablet. The evidence is strong exactly where it was collected and silent everywhere else, and the gap between those two things is where most of the marketing in this industry operates.