# NAD+: A Cited Research Digest of the Coenzyme and Its Precursors > NAD+ is the cell's central redox coenzyme; tissue levels fall with age. Oral precursors NMN and NR raise whole-blood NAD+ dose-dependently in randomized trials. A cited literature digest. The core molecule, the orbiting precursors NMN and NR, the enzymes that spend it, and what the trials actually measured — every quantitative claim cited to a published study. ## In plain English NAD+ (a fuel-handling helper molecule every cell uses to turn food into energy) is one of the busiest molecules in your body. It carries electrons during energy production, and it gets used up by repair-and-maintenance enzymes that keep cells healthy. The amount in your tissues falls as you age. Because swallowing NAD+ itself does not work well — the molecule is too large to absorb intact — most supplements sell a **precursor** (a building block the body converts into NAD+; NMN and NR are the common ones) instead. This page maps the molecule, its precursors, and what controlled studies have measured. ## What is NAD+ NAD+ (nicotinamide adenine dinucleotide) is the central redox coenzyme of every living cell — a non-protein helper molecule that hundreds of enzymes need to do their job [5]. It shuttles electrons through glycolysis, the citric-acid (TCA) cycle and the mitochondrial electron-transport chain, cycling between an oxidized form (NAD+) and a reduced, electron-carrying form (NADH) to drive ATP production [5]. NAD+ is also a *consumed* substrate — not just a catalyst — for three families of signaling enzymes: sirtuins (a family of cellular-maintenance enzymes that cannot work without NAD+), PARPs (DNA-repair enzymes), and CD38 (an enzyme that breaks NAD+ down) [5][6][13]. Its molecular weight is `663.43 Da`, its formula `C21H27N7O14P2`, and its CAS number `53-84-9`. NAD+ is an endogenous metabolite, not an approved drug. ## NAD+ as a dietary supplement: what the studies measured NAD+ and its precursors are sold as **dietary supplements**, not approved drugs, and they are not approved by the FDA to treat, cure or prevent any disease [5]. What controlled trials have reliably shown is narrow and specific: oral precursors raise the amount of NAD+ in blood. In a randomized, double-blind trial in healthy overweight adults, nicotinamide riboside (NR) raised whole-blood NAD+ by `22%`, `51%` and `142%` at `100`, `300` and `1000 mg/day` over 8 weeks [4]. A multicenter, double-blind, dose-response trial of nicotinamide mononucleotide (NMN) at `300-900 mg/day` for 60 days raised blood NAD+ significantly versus placebo at every dose (p ≤ 0.001) and improved walking distance [3]. Whether raising blood NAD+ translates into better hard clinical outcomes — longevity, disease prevention — is a separate, unsettled question. A 2025 narrative review in *Nature Metabolism* concluded that human efficacy data for NAD+ precursors remain limited and that tissue-level NAD+ data are still sparse [14]. The honest summary: the *biomarker* moves; the *clinical payoff* in humans is not yet established. These are [NAD+ precursor research findings](/research), not a recommendation to use any product. ## Why precursors, not NAD+ itself NAD+ itself is large and electrically charged, so it is poorly absorbed intact and is not freely taken up by most cells [8][9]. That is the reason most oral products are precursors rather than NAD+: a precursor is a smaller building block the body converts into NAD+ through its own machinery. The two most-studied oral precursors are NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside), each one or two biochemical steps from NAD+ [8]. Niacin (nicotinic acid) and nicotinamide feed the same pool through other routes [5]. The cell builds NAD+ through several converging pathways: the **salvage** pathway recycles nicotinamide back into NAD+ via the rate-limiting enzyme NAMPT; NR enters through NRK kinases; nicotinic acid enters through the Preiss-Handler route; and tryptophan supplies a de-novo route [5][8]. Because oral NAD+ is poorly absorbed, conflating an oral-NMN or oral-NR study with "taking NAD+" is a category error this digest avoids: those trials measured precursors. The full comparison is on [NMN vs NR precursors](/nmn-vs-nr). ## What the enzymes that spend NAD+ tell us about aging Tissue NAD+ declines with age, and the leading explanations point to the enzymes that consume it [5][10]. In human skin biopsies, NAD+ and NADH fell with age while PARP activity rose and correlated inversely with NAD+ — early direct human-tissue evidence that DNA-damage-driven PARP activation depletes the pool [7]. CD38, an NAD-consuming ectoenzyme, rises with age and inflammation; in mice, deleting CD38 preserved NAD+ and mitochondrial function with age [2]. A review across multiple tissues estimated NAD+ falls by roughly `10-50%` over adult aging, while cautioning that human data are limited relative to rodent data and measurement methods vary [10]. This is the rationale behind precursor supplementation — replace what the consuming enzymes spend — and it is also where the honest gap sits. The mechanism is well mapped in model organisms; the demonstration that raising NAD+ changes human aging outcomes is not. More on [NAD+ and aging](/nad-and-aging). --- An orbital reading of the NAD+ literature — the coenzyme at the core, its precursors NMN and NR held apart from the molecule itself, and the human, rodent and gap evidence each logged to source; no clinic behind the console and nothing here infused, dispensed or sold.