What it is
NAD+ (nicotinamide adenine dinucleotide) is a helper molecule, or coenzyme, present in every living cell. Its main job is to carry electrons. It picks them up as food is broken down and hands them to the machinery in mitochondria that produces the cell’s energy. It is also raw material for enzymes involved in DNA repair and in switching genes on and off, and those enzymes use it up.
Animal studies and some human tissue studies report that NAD+ levels fall with age, which has made it a popular research target. The body builds NAD+ from forms of vitamin B3 and from the amino acid tryptophan. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are building blocks that cells turn into NAD+; they are different compounds from NAD+ itself.
NAD+ (C21H27N7O14P2, 663.4 g/mol) is an adenosine and a nicotinamide riboside joined through a pyrophosphate bridge. The nicotinamide ring accepts a hydride ion to form NADH; the NAD+/NADH couple serves glycolysis, the TCA cycle and complex I of the electron transport chain, while phosphorylation yields NADP+/NADPH for reductive biosynthesis and antioxidant defense. NAD+ is also consumed as a substrate by sirtuin deacylases, poly(ADP-ribose) polymerases and the CD38 and CD157 glycohydrolases, each releasing nicotinamide.
Cells make NAD+ de novo from tryptophan, from nicotinic acid through the Preiss–Handler pathway, and by salvage of nicotinamide through NAMPT to NMN and then NMNAT; NR enters via NR kinases, which phosphorylate it to NMN. Whether intact extracellular NAD+ enters cells is debated; ectoenzymes such as CD38 and CD73 degrade it to smaller precursors. In a pilot study infusing NAD+ at 3 µmol/min for 6 hours (roughly 0.7 g), plasma NAD+ and its metabolites did not rise for the first 2 hours, and the metabolite profile pointed to breakdown by NAD+ glycohydrolase and pyrophosphatase activity (Grant et al., 2019).
Who made it and when
NAD+ is often described as the first coenzyme to be discovered. In 1906 the British biochemists Arthur Harden and William John Young noticed that boiled yeast juice, whose enzymes had been destroyed by heat, still sped up fermentation when added back to fresh yeast juice. The heat-proof ingredient, later called “cozymase”, turned out to contain NAD+. Harden shared the 1929 Nobel Prize in Chemistry with Hans von Euler-Chelpin, who purified it and worked out what it was made of.
In 1936 Otto Warburg’s group showed that the nicotinamide part of the molecule is what carries hydrogen. Interest revived in the 2000s, when NAD+ was linked to enzymes studied in ageing research. It has since become a focus of the supplement and wellness industries. No company has brought an NAD+ drug to FDA approval.
Harden and Young (“The coferment of yeast-juice”, Proc R Soc Lond B, 1906) described a dialysable, heat-stable factor required for alcoholic fermentation by yeast juice, later termed cozymase. Von Euler-Chelpin characterized it as a nucleotide containing adenine, a sugar and phosphate, and the 1929 Nobel Prize in Chemistry was shared by Harden and von Euler-Chelpin for investigations on the fermentation of sugar and fermentative enzymes. Warburg and Christian identified the pyridine (nicotinamide) ring as the hydrogen-transferring component of fermentation coenzymes in 1936 (Helv Chim Acta). Older literature calls the molecule diphosphopyridine nucleotide (DPN) or coenzyme I, and “Coenzyme I for Injection” remains the name of a product tested in Chinese hospital trials.
The modern revival followed the finding that sirtuins are NAD+-dependent deacylases and that NAD+ declines in several tissues of aged rodents (reviewed by Katsyuba and Auwerx, EMBO J 2017). Commercial development has concentrated on precursors: NR and NMN are marketed as dietary ingredients, and FDA’s 2022 exclusion of NMN rested on its prior authorization for investigation as a new drug. No investigational drug program for NAD+ itself with a US sponsor could be verified for this article, and no patent is listed.
What the data say
For NAD+ given directly into a vein, human data are thin. The main published study is a 2019 pilot that tracked blood levels during a six-hour drip; NAD+ disappeared from the bloodstream at first and was broken down, and no health outcome was measured. A small 2026 records review described infusions as uncomfortable for all six NAD+ recipients, with nausea, cramping and chest pressure that resolved after the infusion ended. No controlled trial showing an effect of NAD+ infusion on any health outcome was found.
The precursors have more data. In a small controlled trial, oral NR raised NAD+ levels in blood cells. An early Parkinson disease study reported higher NAD+ in the brain with NR, and a trial in women with prediabetes reported better muscle insulin sensitivity with NMN. A 410-person Parkinson trial of NR finished in 2025; published results were not found when this was written.
Direct NAD+: Grant et al. (Front Aging Neurosci 2019) infused NAD+ at 3 µmol/min for 6 hours and found no change in plasma NAD+ or metabolites for the first 2 hours, then more urinary methylnicotinamide and NAD+ by 6 hours; no clinical endpoint was assessed. A 2026 retrospective chart review by staff of a wellness provider (Reyna et al., Front Aging) reported moderate-to-severe GI symptoms and chest pressure in all 6 recipients of 500 mg NAD+ IV daily for 4 days (mean infusion 97 vs 37 minutes with IV NR). No registered phase 2 or 3 trial of IV NAD+ was found.
Precursors: NR was well tolerated and raised NAD+ metabolism in a 2 × 6-week crossover in healthy middle-aged and older adults (Martens et al., Nat Commun 2018). NADPARK (phase 1, n=30) gave NR 1,000 mg daily for 30 days in newly diagnosed, treatment-naive Parkinson disease and reported a significant but variable rise in cerebral NAD (Brakedal et al., Cell Metab 2022). NOPARK (NCT03568968; phase 3; n=410; 500 mg twice daily for 52 weeks) completed in June 2025. A 10-week trial of NMN in postmenopausal women with prediabetes reported increased muscle insulin sensitivity (Yoshino et al., Science 2021).
Regulatory picture
Three separate facts. Approval: no FDA-approved drug contains NAD+. Compounding: injectable NAD+ in the US is made by compounding pharmacies. The FDA lists NAD+ as “under evaluation” (Category 1) for its bulk-ingredient list, which means no final decision has been made. In 2017 an FDA advisory committee voted against adding NAD and NADH to that list, in line with the FDA’s own proposal; the vote is not binding, and the FDA has not finalized a decision. In October 2024 the FDA warned compounders against using food-grade NAD+ for injections after reports of chills, shaking and vomiting in patients.
The precursors have their own history. In 2022 the FDA told supplement-ingredient makers that NMN could not be sold as a dietary supplement because it had first been authorized for study as a drug. After an industry petition and a lawsuit, the FDA reversed that position in September 2025 and in December 2025 began reinstating earlier NMN notifications. That decision concerns NMN, not NAD+.
Approval: none. NAD+ (nadide) is not the active ingredient of any FDA-approved product; the registered US studies found are small non-phase trials (NCT06382688, NCT06919328).
Compounding: FDA’s nominations list, updated 2026-05-14, places nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide disodium reduced (NADH) in Category 1, while a separate “beta-nicotinamide adenine dinucleotide disodium salt trihydrate” nomination sits in Category 3. NAD+ is not on the bulks list in 21 CFR 216.23; under FDA’s interim policy the agency does not intend to act against Category 1 substances while under evaluation, if other conditions are met. At the 2017-05-08 Pharmacy Compounding Advisory Committee meeting FDA proposed that neither NAD (reviewed for fatigue in multiple sclerosis) nor NADH (chronic fatigue syndrome) be included, and the committee voted 3–7 and 0–9 against inclusion; FDA has not completed rulemaking on either. Because that status is interim, this article records compounding as unknown. On 2024-10-30 FDA stated that food-grade NAD+ is unsuitable for sterile compounding without processing.
Precursors: from 2022-10-11 FDA told firms that had filed NMN notifications (including NDI 1247 and 1259) that NMN was excluded from the dietary-supplement definition under the drug-preclusion clause. Two industry groups petitioned on 2023-03-07, and one (the NPA) later sued. On 2025-09-29 FDA partly granted the petition, dropping its requirement that prior supplement marketing be lawful and finding NMN marketed as a supplement in the US as early as 2017, before its IND authorization. Reinstatement letters began on 2025-12-02.
