NAD+ is the cell's redox coenzyme that sirtuins, PARP and CD38 all consume.

The short version

NAD+ (nicotinamide adenine dinucleotide — a fuel-handling helper molecule every cell uses to turn food into energy) does two jobs at once. It carries electrons through metabolism to make ATP, and it is the raw material a set of cellular-maintenance enzymes burn through to do their work. Tissue levels of NAD+ fall as you age. You can raise blood NAD+ in people, but mostly through precursors — building blocks like NMN and NR that the body converts into NAD+ — because NAD+ itself is too large and too charged to absorb well by mouth. This page reports what specific studies measured. It is a research digest, not medical advice, and nothing here is sold.

What is NAD+?

NAD+ is a dinucleotide coenzyme — a small molecule, MW 663.43 Da, formula C21H27N7O14P2, CAS 53-84-9 — built from a nicotinamide ring and an adenine ring joined by two bridging phosphates. A coenzyme is a non-protein helper molecule an enzyme needs to do its job, and NAD+ is the helper for hundreds of oxidoreductase reactions ^[9]. It exists in two interconverting forms: the oxidized, electron-accepting NAD+ and the reduced NADH. Picture it as a rechargeable shuttle — NAD+ picks up electrons stripped from food to become NADH, then drops them off at the mitochondria to help generate energy, and the cell flips the same molecule back and forth thousands of times a second. A landmark review describes NAD+ as a coenzyme present in all living cells that both carries electrons in reduction–oxidation reactions and serves as a cosubstrate for sirtuins and poly(ADP-ribose) polymerases, with cellular concentrations changing during aging ^[8].

The distinction that runs through this whole site: NAD+ is the coenzyme itself. NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are its precursors — molecules the body converts into NAD+. They are not NAD+, and a trial of oral NMN or NR is not a trial of "taking NAD+." Keeping what is NAD+ separate from its building blocks is the single most important idea here, and it is the one every page on this site holds to.

What the research has actually measured

The reproducible human finding is pharmacodynamic: oral NAD+ precursors reliably and dose-dependently raise the amount of NAD+ circulating in whole blood. In healthy overweight adults, eight weeks of NR raised whole-blood NAD+ by 22%, 51% and 142% at 100, 300 and 1000 mg/day respectively, with no flushing and no significant adverse-event difference from placebo at any dose ^[4]. In a multicenter, double-blind, placebo-controlled trial, oral NMN at 300, 600 and 900 mg/day for 60 days significantly raised blood NAD+ at days 30 and 60 across every NMN group versus placebo (p≤0.001) ^[3].

Functional endpoints are narrower and more specific. Ten weeks of oral NMN at 250 mg/day increased muscle insulin sensitivity — measured by a hyperinsulinemic-euglycemic clamp, the reference method — in prediabetic, postmenopausal women, with no change in body composition or HbA1c ^[1]. The same multicenter NMN trial reported improved walking distance versus placebo ^[3]. These are the measured results, drawn from human clinical trials of NAD+ precursors, not from rodent extrapolation. They are not approved treatments, and none of them is a claim that NAD+ treats, reverses or prevents any disease.

NAD+ as a supplement: why most oral products are precursors

NAD+ is marketed as a dietary supplement, not a drug, and it is not FDA-approved for any disease. But oral "NAD+" itself is a poor delivery strategy: the intact coenzyme is large, charged and not freely taken up by cells. An in-vitro study of human skin fibroblasts found that extracellular NAD was degraded by surface ecto-enzymes into nicotinamide, NMN and purine metabolites before any uptake, with adenosine — not NAD+ — the principal product the cells absorbed ^[12]. That is why rational oral products are precursors: NMN, NR, or the vitamin-B3 forms niacin and nicotinamide, which the body converts into NAD+ through dedicated biosynthesis pathways such as the salvage and Preiss-Handler routes ^[10].

The precursor market carries one open regulatory question. The FDA has taken the position that NMN is excluded from the dietary-supplement definition because it was authorized for investigation as a drug — a marketplace dispute over NMN's supplement status, not a finding that NMN is banned or illegal. Supplement-grade purity also varies between products, and third-party testing is not guaranteed.

Oral, IV, and the gap between them

The same word — "NAD+" — covers two very different products with very different evidence. The oral-precursor route (NMN, NR, niacin) carries the bulk of the controlled human data and reliably raises blood NAD+ ^[4][3]. The IV/injectable route is the one most aggressively marketed as "NAD+ therapy," yet it has the weakest controlled evidence: infused NAD+ is cleared from plasma within about two hours ^[12], and a compounded injectable NAD+ product drew an FDA Class I recall for endotoxin contamination — a documented quality risk, not an approval. Across both routes, the cited trials measured surrogate and functional endpoints; they did not show NAD+ treats, reverses or prevents any disease, and a 2025 review concluded that human efficacy for hard clinical outcomes remains preliminary ^[14]. The doses used in NAD+ studies are reported here strictly as study parameters.

The mechanism in one paragraph

NAD+ is consumed, not just cycled. Three enzyme families spend it: the sirtuins (SIRT1–SIRT7, NAD+-dependent enzymes that strip chemical tags off proteins to regulate metabolism, stress resistance and DNA repair), PARP1 (a DNA-repair enzyme that burns large amounts of NAD+ when DNA is damaged), and CD38 (a surface enzyme that breaks NAD+ down and rises with age and inflammation) ^[5]. Because these enzymes draw from one shared NAD+ pool, they compete — and as CD38 activity climbs with age, less NAD+ is left for the sirtuins ^[2]. That competition for a single, depletable pool is the throughline of the mechanism, and it is why "more NAD+" is biologically plausible without being a proven outcome. The full account lives on sirtuins and NAD+, and the age-related decline on the page covering why NAD+ declines with age.