What it is
NAD+ (nicotinamide adenine dinucleotide) is a helper molecule. Scientists call this kind of helper a coenzyme. It is found in every living cell.
Its main job is to carry electrons. It picks them up as the body breaks down food. Then it passes them to the cell’s power plants (mitochondria). These make the cell’s energy. NAD+ is also used by enzymes that repair DNA. Other enzymes use it to switch genes on and off. These enzymes use NAD+ up.
Animal studies and some human tissue studies say NAD+ levels drop with age. That is one reason researchers are interested in it. The body makes NAD+ from forms of vitamin B3. It can also make it from tryptophan, an amino acid (a building block of protein). Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are building blocks that cells turn into NAD+. They are not the same thing as NAD+.
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 called the first coenzyme ever found. In 1906, two British scientists made the discovery. Their names were Arthur Harden and William John Young. They boiled yeast juice, which destroyed its enzymes. Yet the boiled juice still sped up fermentation when added to fresh yeast juice. The ingredient that survived the heat was later named “cozymase”. It turned out to contain NAD+.
Harden shared the 1929 Nobel Prize in Chemistry. He shared it with Hans von Euler-Chelpin. Von Euler-Chelpin purified the substance and worked out what it was made of.
In 1936, Otto Warburg’s team found which part of the molecule carries hydrogen. It is the nicotinamide part. Interest grew again in the 2000s. That is when NAD+ was linked to enzymes studied in ageing research. Since then, the supplement and wellness industries have focused on it. 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
There is very little human data on NAD+ given into a vein. The main study is a small test study (a pilot) from 2019. It tracked blood levels during a six-hour drip. At first, NAD+ vanished from the blood. It was broken down. The study did not measure any health result.
A small 2026 review of patient records looked at 6 people who got NAD+ drips. All 6 found the drips uncomfortable. They had nausea, cramps and chest pressure. These went away after the drip ended. No controlled trial has been found that shows an NAD+ drip helps any health problem. A 2026 review of 113 studies (33 in people, 80 in rodents) found no trial of NAD+ drips or shots that measured health results. The first mid-stage (Phase 2) trial of NAD+ drips, in children with weak heart pumping in China, was registered in September 2026 and had not started.
There is more data on the building blocks (NR and NMN). In a small controlled trial, NR taken by mouth raised NAD+ in blood cells. An early study in Parkinson disease reported more NAD+ in the brain with NR. A trial in women with prediabetes reported that their muscles responded better to insulin with NMN. A larger Parkinson trial of NR (410 people, 1 year) was published in October 2026. NR did not help: movement and other symptom scores were slightly worse with NR than with placebo. Note that NR is a building block, not NAD+ itself.
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). A systematic review of 113 studies (33 human, 80 rodent; Gallagher and Emmanuel, Ageing Res Rev 2026;116:103057) found no eligible outcomes trial of intravenous or intramuscular NAD+ and judged the evidence for anti-ageing efficacy inconclusive. The first registered phase 2 trial of IV NAD+, PEDI-NAD (NCT07839130; 180 children with LVEF below 55%; 2 or 4 mg/kg/day for 7 days vs saline; Beijing Children’s Hospital), was posted in September 2026 and was not yet recruiting as of November 2026.
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; NR 500 mg twice daily for 52 weeks, n=206, vs placebo, n=204) was published in JAMA on 2026-10-08 (Brakedal et al., doi 10.1001/jama.2026.18828): the MDS-UPDRS adjusted mean difference was +2.72 points favouring placebo (95% CI 0.47–4.98; P=.02), the NMSS difference +4.22 (1.07–7.37), and serious adverse events occurred in 8.3% vs 14.1%. NR is an NAD+ precursor, not NAD+ itself. A 10-week trial of NMN in postmenopausal women with prediabetes reported increased muscle insulin sensitivity (Yoshino et al., Science 2021).
Regulatory picture
There are three separate things to know.
Approval: No FDA-approved drug contains NAD+.
Compounding: In the US, NAD+ shots are made by compounding pharmacies. These are pharmacies that mix their own products. The FDA keeps a list of bulk ingredients these pharmacies may use. NAD+ is marked “under evaluation” (Category 1) for that list. This means no final decision has been made. In 2017, an FDA advisory panel voted against adding NAD and NADH to the list. The FDA had proposed the same thing. But the vote does not have to be followed, and the FDA has not made a final decision.
Warning: In October 2024, the FDA warned compounding pharmacies. It said not to use food-grade NAD+ for shots. This came after patients reported chills, shaking and vomiting. In January 2026, the FDA sent a warning letter to GenoGenix, a large-scale compounder. It said NAD+ was not an allowed ingredient for that kind of facility, that 3 patients given NAD+ from one vial went to the emergency room, and that finished products were not tested. The firm’s NAD+ vials had been recalled in 2025 for endotoxin (Class I, the most serious level). In April 2026, the FDA warned another compounder, ProRx, about missing information on its NAD+ label. In September 2026, Apothecary Pharma recalled an NAD+ injection because sterility could not be assured.
The building blocks have their own story. In 2022, the FDA said NMN could not be sold as a supplement. Its reason was that NMN had first been allowed to be studied as a drug. An industry group then filed a request and a lawsuit. In September 2025, the FDA reversed its position. In December 2025, it began restoring earlier NMN filings. This decision is about 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. Enforcement since then: a 2026-01-20 warning letter to the 503B outsourcing facility GenoGenix LLC lists NAD+ among bulk substances not eligible for 503B use, calls its NAD+ product adulterated under section 501(c), records three patients sent to the emergency room after NAD+ from the same vial, and notes the absence of finished-product testing; the firm’s NAD+ for Injection (100 and 200 mg/mL, lot GG121624-023) was recalled for elevated endotoxin (initiated 2025-07-30, Class I on 2025-10-21, D-0094-2026) alongside a Class II recall (D-0065-2026) for lack of sterility assurance. A 2026-04-07 warning letter to ProRx LLC (503B, Exton, Pennsylvania) cites its “Nicotinamide Adenine Dinucleotide Injection, 1200mg” label for lacking “Not for Resale” and the established name. Apothecary Pharma LLC recalled NAD+ Injection 200 mg/mL (lot AP-202647) for lack of sterility assurance (initiated 2026-09-24, Class II on 2026-10-08, D-0037-2027).
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.
