NAD+/NMN

NAD+ is the most legitimate longevity target in this reference set and the most commercially exploited. These two things are not in tension — the legitimacy is precisely what made it commercially exploitable. The biology is real. The commercial claims have outrun the clinical evidence. Both deserve to be said clearly.

The central tension resolved: NAD+ declines with age in human tissue. The decline contributes to mitochondrial dysfunction, reduced DNA repair, impaired sirtuin signaling, and accelerated aging phenotypes. Restoring NAD+ in old mice reverses multiple aging phenotypes in multiple independent labs. The animal evidence is compelling and replicable. Human clinical trials find that NMN and NR reliably raise blood NAD+ levels and produce modest improvements in metabolic function and physical performance in specific populations. Independent meta-analyses in 2024-2025 consistently find that 'most clinically relevant outcomes were not significantly different' from placebo and that 'exaggeration of benefits may exist in the field.' Two of the most prominent voices advocating for specific NAD+ precursors — Sinclair for NMN, Brenner for NR — both have direct commercial interests in the precursor they advocate for. The truth likely lives between their positions: NAD+ supplementation probably does something modestly beneficial for aging humans, probably less dramatically than the commercial discourse implies, and probably through mechanisms that the current clinical trials haven't been long enough or large enough to fully characterize.

What the evidence currently supports with confidence: oral NMN or NR reliably raises blood NAD+; modest improvements in insulin sensitivity, physical performance, and liver enzymes in specific populations; a good safety profile. What the evidence does not support: 'reversing aging,' dramatic longevity extension, or a clear clinical superiority of expensive NMN/NR over cheap niacinamide for most applications.