NAD+ levels drop 50% between age 20 and 60. Three main strategies exist to restore them: NAD+ IV infusions, NMN supplements, and NR supplements. A practical comparison of the evidence, costs, and trade-offs.
NAD+ is one of the most discussed molecules in longevity science — and one of the most confusing to supplement. The fundamental biology is not in dispute: NAD+ levels fall roughly 50% between age 20 and 60, and this decline is associated with mitochondrial dysfunction, reduced DNA repair capacity, impaired sirtuin activity, and accelerated cellular aging. The question is how to raise them effectively.
Three main approaches exist in 2026: NAD+ IV infusions (at longevity clinics), NMN (nicotinamide mononucleotide) supplements, and NR (nicotinamide riboside) supplements. They work through different biochemical pathways, have different bioavailability profiles, different costs, and different evidence bases. Here is a clear-eyed comparison.
NAD+ is a coenzyme required for hundreds of metabolic reactions. But its longevity relevance is primarily through three mechanisms:
Sirtuins: A family of seven protein deacylases (SIRT1–7) that regulate gene expression, DNA repair, inflammation, and metabolic adaptation. All seven sirtuins require NAD+ as a co-substrate. When NAD+ falls, sirtuin activity falls. David Sinclair's foundational research in this area established sirtuins as potential longevity regulators.
PARP enzymes: DNA repair proteins that consume large amounts of NAD+, especially in response to oxidative DNA damage. As we age and accumulate more DNA damage, PARP demand increases, further depleting NAD+. Supplementing NAD+ precursors can replenish the pool available for repair.