NAD+

Properties

Substance class	Not a peptide and not a supplement ingredient by origin — a dinucleotide coenzyme present in living cells. A peer-reviewed review in Nature Reviews Molecular Cell Biology opens by stating that "Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions, making it central to energy metabolism", and that it "is also an essential cofactor for non-redox NAD+-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases". That is the whole of what this file asserts about what the molecule does.	source
Distinction from its precursors	READ THIS BEFORE READING ANYTHING ELSE ON THIS PAGE. Four distinct molecules are sold and discussed under NAD-related names, and PubChem records them as four separate compounds with four different formulas. NAD+ itself is CID 5892, formula C21H27N7O14P2. Nicotinamide riboside (NR) is CID 439924, formula C11H15N2O5+. Nicotinamide mononucleotide (NMN) is CID 14180, formula C11H15N2O8P. Nicotinamide is CID 936, formula C6H6N2O, and nicotinic acid is CID 938, formula C6H5NO2. NR and NMN are precursors sold as supplements; nicotinamide and nicotinic acid are the vitamin B3 forms. They are chemically different substances with separate published literatures, and a result obtained with one is not a result for another.	source
Precursor identifiers	Nicotinamide riboside is PubChem CID 439924, formula C11H15N2O5+, molecular weight 255.25 g/mol, CAS 1341-23-7, and appears in PubChem's synonym list under the trade names Niagen and TruNiagen. Nicotinamide mononucleotide is PubChem CID 14180, formula C11H15N2O8P, molecular weight 334.22 g/mol, CAS 1094-61-7. Neither shares NAD+'s formula, mass or CAS number. Recorded here so that a figure found under a NAD-adjacent name can be assigned to a specific molecule rather than assumed.	source
Vitamin b3 relationship	The Institute of Medicine's Dietary Reference Intakes chapter states that "The term niacin refers to nicotinamide (nicotinic acid amide), nicotinic acid (pyridine-3-carboxylic acid), and derivatives that exhibit the biological activity of nicotinamide", and that niacin functions through two coenzymes, "nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)". The same chapter gives the tryptophan conversion as "60 mg of tryptophan = 1 mg of niacin = 1 mg of niacin equivalents", an adult Recommended Dietary Allowance of "16 mg/day of NEs for men and 14 mg/day of NEs for women", and a Tolerable Upper Intake Level for adults of 35 mg, based on flushing as the critical adverse effect. Those figures are nutrition reference values for the vitamin, not for this compound, and are recorded to keep the two apart.	source
Other names	Unlike most compounds in this category, this one carries assigned names from the naming bodies. FDA's substance record gives the preferred substance name NADIDE and records nadide as an INN, a USAN and a JAN, with an entry in the WHO Drug Dictionary. PubChem's synonym list for the same structure includes "nicotinamide adenine dinucleotide", "beta-NAD", "coenzyme I", "diphosphopyridine nucleotide" and "cozymase I". An assigned nonproprietary name is a naming fact, not an approval.	source
Cas number	53-84-9	source
Unii	0U46U6E8UK	source
Molecular formula	C21H27N7O14P2	source
Molecular weight	663.4 g/mol	source
Molecular data independent cross check	PubChem's record for CID 5892, titled "Nadide", carries the molecular formula C21H27N7O14P2, matching FDA's substance record, and lists CAS 53-84-9 and UNII 0U46U6E8UK among its synonyms. Recorded as a cross-check on the FDA record, not as an independent measurement — both describe the same structure.	source
Appearance	PROVENANCE FIRST. PubChem's physical-description field for CID 5892 reads "Highly hygroscopic white solid; [Merck Index] White powder; [Sigma-Aldrich MSDS]". Those are a reference work and a supplier safety data sheet, not a published characterisation study and not a determination by any regulator. There is no approved product label and no United States Pharmacopeia monograph for this substance to check it against.	source
Storage	Stability is the specific thing FDA faulted, and it did so twice. In its September 5, 2019 proposed rule evaluating NAD as a bulk drug substance, FDA wrote that NAD "is well characterized physically and chemically, but it degrades substantially when exposed to light, moisture, alkaline pH, or standard room temperatures and would not be stable under ordinary storage conditions absent multiple compensatory measures". FDA recorded the same finding separately for the reduced form, NADH. No numeric shelf life, no in-use period and no reconstituted-solution condition is established by any source located during data entry: there is no pharmacopoeial monograph and no approved product label for this substance, so no body with standing to determine handling conditions has done so. Any storage figure circulating for this compound traces to a supplier page rather than to a determination by anyone.	source
Mechanism as described in cited work	Two roles, both descriptive. Covarrubias 2021 describes NAD+ as a coenzyme for redox reactions and as an essential cofactor for non-redox enzymes including sirtuins, CD38 and poly(ADP-ribose) polymerases, and states that NAD+ "can directly and indirectly influence many key cellular functions, including metabolic pathways, DNA repair, chromatin remodelling, cellular senescence and immune cell function". Liu 2018, using isotope tracers rather than concentration measurements, reports that in cell lines NAD "was made from nicotinamide and consumed largely by PARPs and sirtuins", and that in vivo NAD "was made from tryptophan selectively in the liver, which then excreted nicotinamide". This is cell biology, described as its authors described it.	source
Route dependence of precursor metabolism	The single most important pharmacology finding for reading this literature, and it is about the precursors rather than the coenzyme. Liu 2018 reports that "Intravenous administration of nicotinamide riboside or mononucleotide delivered intact molecules to multiple tissues, but the same agents given orally were metabolized to nicotinamide in the liver." Oral precursor and intravenous precursor are therefore not the same experiment, and neither is an experiment on NAD+ given directly. The same paper reports that NAD fluxes varied widely across tissues, with high flux in the small intestine and spleen and low flux in skeletal muscle.	source
Fate of directly administered nad in humans	Measured once, in a small pilot study, and the result was not what the consumer framing implies. Grant 2019 documented plasma and urine changes during and after a 6 h 3 micromol/min intravenous NAD+ infusion, and states that "no data are currently available on the fate of directly infused NAD+ in a human cohort" before its own measurement. Its reported findings were that "at an infusion rate of 3 micromol/min NAD+ is rapidly and completely removed from the plasma for at least the first 2 h", that "the profile of metabolites is consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity", and that urinary excretion products included NAD+ itself and methylnicotinamide but not nicotinamide. The authors describe the absence of any change in plasma NAD+ or its metabolites until after 2 h as surprising. This is a metabolite-tracking study, not a study of any effect in a person.	source
Approval status	No approved drug product containing NAD+ was located anywhere during data entry, and the regulatory record is consistent with there being none. FDA has evaluated this substance only as a bulk drug substance nominated for use in compounding, and in that evaluation it proposed not to add it to the 503A Bulks List; in a 2026 warning letter FDA states it does not appear on the 503B bulks list either. An assigned INN, USAN and JAN ("nadide") records that naming bodies have named the molecule; it is not a marketing authorisation and must not be read as one. This entry states what the regulatory record shows rather than asserting a worldwide negative that no single source establishes.	source
Fda 503a bulks list status	Proposed for exclusion, and the advisory committee agreed. In a proposed rule published in the Federal Register on September 5, 2019, FDA listed nicotinamide adenine dinucleotide (NAD) among 26 substances it proposed not be included on the 503A Bulks List. FDA's stated grounds were that nonclinical data in the literature "are inadequate to characterize the potential toxicity profile for NAD", that it "did not find sufficient clinical data about NAD to evaluate whether it is safe for use in compounded drug products", and that it identified "no published studies that support the use of NAD for the treatment of fatigue in patients with multiple sclerosis" — the use for which it had been nominated. FDA's conclusion was that "On balance, the physiochemical characteristics, safety, effectiveness, and historical use of NAD weigh against inclusion of this substance on the 503A Bulks List", and it records that "At its meeting on May 8, 2017, the PCAC voted not to include NAD on the list". This was a proposed rule; FDA's published 503A Bulks List page does not name NAD, and this file does not assert whether the proposal was finalised.	source
Fda 503b bulks list status	Not on it. In a warning letter dated January 20, 2026 from the Center for Drug Evaluation and Research, FDA wrote that a firm's "facility compounded drug products using bulk drug substances that are not eligible for the use in compounding under section 503B, including 5-amino-1-methylquinolinium iodide (5-Amino-1MQ) and nicotinamide adenine dinucleotide (NAD+)", and that such products "are not eligible for the exemptions provided by section 503B, because 5-Amino-1MQ and NAD+ do not appear on the 503B bulks list and are not used to compound a drug that appears on the drug shortage list". The determination is about that firm's products; the statement about the bulks list is a statement about the substance.	source
Fda statement naming intravenous nad	FDA has published a statement that names this substance and this route directly. On a compounding page whose content is current as of 10/30/2024, FDA states that "The agency is aware of compounders using food-grade nicotinamide adenine dinucleotide (NAD+) sold by repackagers to make intravenous products", and that "Ingredients identified as food grade are not suitable for compounding sterile drugs without appropriate processing, due to the high risk of contamination with microbes and endotoxins, which can harm patients". FDA states in the same place that it "has received adverse event reports following use of NAD+ injectable drugs, including severe chills, shaking, vomiting and fatigue with some requiring medical treatment", and that "These reactions are consistent with excessive levels of endotoxins".	source
Fda enforcement finding on a compounded nad product	One documented case with a measured number attached. In the January 20, 2026 warning letter, FDA records that the firm "initiated a complaint investigation after receiving a notification from a healthcare provider that three patients had developed adverse symptoms, including low blood pressure, uncontrollable shaking, shivers, and body aches shortly after or during the administration of a product compounded by your firm containing NAD+", that testing found the product contained "excessive bacterial endotoxins with a reported value of 3,360 EU/mL", and that the firm had "never conducted media fills" and "never performed personnel or environmental monitoring during the production of drug products". The firm ceased operations and recalled its sterile products on July 30, 2025, citing lack of sterility assurance or microbial contamination. This is a finding about one firm's manufacturing, not about the molecule.	source
Fda significant safety risks listing	Absent, and the absence was checked rather than assumed. FDA's page of bulk drug substances that may present significant safety risks, content current as of 04/22/2026, names neither nicotinamide adenine dinucleotide, NADH, nicotinamide riboside nor nicotinamide mononucleotide in either of its tables. Not appearing on a risk list is not a safety finding; it records only that FDA has not placed the substance there.	source
Nmn united states regulatory position	This is the one people get wrong, and it reversed. In a response to a citizen petition from the Natural Products Association and the Alliance for Natural Health USA under Docket Number FDA-2023-P-0872, signed by Donald Prater, DVM, Principal Deputy Director for Human Foods, FDA granted the petition in part and denied it in part, and amended its earlier determination that NMN is excluded from the dietary supplement definition. FDA's reasoning, verbatim: "although NMN was authorized for investigation as a new drug and substantial clinical investigations of NMN have been instituted and made public, NMN was marketed as a dietary supplement in the United States before such authorization". FDA added that it "will no longer evaluate whether the dietary supplement or food was lawfully marketed when making a determination under the race-to-market clause", and that it "is aware of evidence that NMN was marketed as a dietary supplement in the United States as early as 2017". FDA also records that "NMN and MIB-626 have the same chemical structure, as confirmed by FDA's review of the relevant INDs, and, thus, are the same article". PROVENANCE CAVEAT: the letterhead date on the published PDF reads September 29, 2029, which cannot be correct; this entry therefore identifies the response by its docket number and signatory rather than by date. None of this concerns NAD+ itself — it is a determination about a precursor.	source
Nr united states regulatory position	Different again, and again not about NAD+. FDA's GRAS notice inventory records GRN No. 635 for nicotinamide riboside chloride, notified by ChromaDex, Inc., for use as a "Source of vitamin B3 in vitamin waters, protein shakes, nutrition bars, gum, chews, and powdered beverages at a maximum level of 0.0057% by weight as consumed", closed on August 3, 2016 with the response "FDA has no questions". A no-questions letter on a GRAS notice for a food use is not an approval of a drug, and it says nothing about the coenzyme or about any intravenous product.	source
Clinical trial registrations	READ THE BREAKDOWN, NOT THE HEADLINE NUMBER. A query of the ClinicalTrials.gov API on 2026-09-19 for "nicotinamide adenine dinucleotide" as an intervention returned 264 studies. Inspecting the registered intervention names of all 264: 50 name nicotinamide riboside or Niagen, 10 name nicotinamide mononucleotide or NMN, and only 14 carry an intervention name containing NAD or nicotinamide adenine dinucleotide at all. One of those 14, NCT02010151, is a cardiopulmonary resuscitation study in which NAD stands for Neighborhood Access Defibrillation. Several of the remainder are oral consumer products named "NAD+" rather than administration of the coenzyme. The registry reflects the same pattern as the literature: the name says NAD+, the intervention is usually something else.	source
Registered head to head studies of the route	Two registered studies compare intravenous NAD+ against intravenous nicotinamide riboside, both sponsored by the Nutraceuticals Research Institute and neither with results posted. NCT06382688, "The Effects of IV Administration of ChromaDex's Niagen, Nicotinamide Riboside Chloride as Compared to IV Administration of NAD+", has an actual enrolment of 53 and a registry status of unknown. NCT06919328, "Absorption and Tolerability of Injectable Administration of Niagen+, Nicotinamide Riboside Chloride, a Specialized Form of Vitamin B3, as Compared to NAD+", has an estimated enrolment of 70 and is recruiting. Both are registered as not applicable for phase and both list their comparators as dietary supplements. A registration is a plan, not a result.	source

What the research does not show

The central limitation is not that the evidence is weak. It is that most of the evidence is about a different molecule. Of the human trials routinely cited for "NAD+" — Trammell 2016, Dollerup 2018, Martens 2018, Conze 2019, Elhassan 2019, Remie 2020, Yoshino 2021 — every one administered nicotinamide riboside or nicotinamide mononucleotide, not NAD+. PubChem records NAD+, NR and NMN as three separate compounds with three different molecular formulas. A finding about a precursor is not a finding about the coenzyme, and this page does not conflate them. source
The naming problem is not hypothetical; it reaches into the trial registry. NCT02942888 is registered under the title "The Effects of NAD on Brain Function and Cognition" with the condition "NAD", and its registered interventions are oral nicotinamide riboside (Niagen) and a placebo compounded by ChromaDex. Anyone citing that study as evidence about NAD+ is citing a study of an oral precursor. Read the intervention field, not the title. source
Route is not a detail here; it changes what reaches tissue. Liu 2018 reports that nicotinamide riboside and nicotinamide mononucleotide given intravenously delivered intact molecules to multiple tissues, while the same agents given orally were metabolised to nicotinamide in the liver. Oral precursor, intravenous precursor and intravenous coenzyme are three different experiments, and results from one do not transfer to another. source
What is actually known about NAD+ given directly to a person is one pilot study. Grant 2019 states that before its own work "no data are currently available on the fate of directly infused NAD+ in a human cohort", and reports that during a 6 h infusion NAD+ was rapidly and completely removed from plasma for at least the first 2 h, with a metabolite profile the authors read as consistent with glycohydrolase and pyrophosphatase activity. That is a bioavailability question raised, not answered — and it is the entire human dataset on the coenzyme's fate by that route. source
The comparative tolerability data that exists is retrospective, small, and produced by the company selling the service. Reyna 2026 reviewed electronic medical records from a commercial wellness setting in which clients received four consecutive days of 500 mg NAD+ or NR intravenously. Participants receiving NAD+ reported moderate to severe gastrointestinal symptoms, increased heart rate and chest pressure during infusions, with infusion times averaging 97 min against 37 min for NR. The authors' own conflict-of-interest statement records that seven of them were employed by the company whose clients were reviewed. A record review is not a controlled trial. source
Null and contradictory results exist in the precursor literature and are rarely cited alongside the positive ones. Dollerup 2018, a randomised placebo-controlled trial in 40 obese, insulin-resistant men over 12 weeks, concluded that NR "does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men", with no effect on resting energy expenditure, lipolysis, lipid oxidation or body composition. Remie 2020, a crossover trial in 13 overweight or obese volunteers, found no effect of NR on insulin sensitivity, mitochondrial function, hepatic or intramyocellular lipid, cardiac energy status, ejection fraction, ambulatory blood pressure, inflammation markers or energy metabolism. Both raised the muscle or blood NAD+ metabolome and neither produced the downstream effect the rodent work predicted. source
Raising a biomarker is not the same as changing an outcome, and the precursor literature separates the two cleanly. Conze 2019 reported that NR dose-dependently raised whole blood NAD+ by 22%, 51% and 142% across its three doses within 2 weeks. Elhassan 2019 reported that oral NR elevated the muscle NAD+ metabolome in 12 aged men without altering muscle mitochondrial bioenergetics. The biomarker moved in both; that is what those papers establish. source
A large part of this literature is funded by, or authored by people with an interest in, the products it studies. Trammell 2016 discloses that three authors own stock in ChromaDex, the supplier of the NR and the sponsor of the clinical study, and that one author is chief scientific adviser to a company selling NR supplements. Conze 2019 discloses that two authors are ChromaDex employees, that a third is the inventor of intellectual property licensed by ChromaDex, and that ChromaDex funded the study. This is normal for a commercial ingredient and is not an accusation; it does mean the most-cited results are not independent replications. source
There is no established storage condition, in-use period or shelf life, and FDA identified stability as the specific problem. FDA's 2019 evaluation states that NAD "degrades substantially when exposed to light, moisture, alkaline pH, or standard room temperatures and would not be stable under ordinary storage conditions absent multiple compensatory measures". No pharmacopoeial monograph and no approved product label exists for this substance, so nobody with the standing to determine handling conditions has done so. source
FDA's own assessment of the evidence, on the record, was that there was not enough of it to judge. Evaluating NAD as a bulk drug substance, FDA wrote that nonclinical data in the literature "are inadequate to characterize the potential toxicity profile for NAD" and that it "did not find sufficient clinical data about NAD to evaluate whether it is safe for use in compounded drug products". Its advisory committee voted not to add the substance to the 503A Bulks List on May 8, 2017. That assessment is about the coenzyme itself, not about any precursor. source
Product quality, not pharmacology, is where the documented harm in this category sits. FDA states it is aware of compounders using food-grade NAD+ to make intravenous products and that food-grade ingredients are not suitable for compounding sterile drugs, and reports adverse event reports following use of NAD+ injectable drugs including severe chills, shaking, vomiting and fatigue, some requiring medical attention, which it describes as consistent with excessive endotoxin levels. A 2026 warning letter records a compounded NAD+ product testing at 3,360 EU/mL of bacterial endotoxins and three patients developing symptoms after administration from the same vial. source
The trial registry overstates how much of this work is about the coenzyme. A ClinicalTrials.gov intervention query for "nicotinamide adenine dinucleotide" returns 264 studies, of which only 14 name NAD or nicotinamide adenine dinucleotide in an intervention at all — and one of those 14 is a resuscitation study using NAD as an unrelated acronym. Counting registry hits by compound name measures naming conventions, not evidence. source
The regulatory position of the precursors is not the regulatory position of the coenzyme, and the precursors do not share one with each other. Nicotinamide riboside chloride has a closed GRAS notice with a no-questions response for specified food uses. NMN's status as a dietary ingredient was determined, reversed on a citizen petition, and rests on a race-to-market argument about pre-2017 marketing rather than on any safety finding. NAD+ itself has neither; FDA has considered it only as a bulk drug substance for compounding and proposed not to list it. Three molecules, three unrelated regulatory tracks. source
Long-term safety is not established for NAD+ administered by any route. No controlled long-term study of the coenzyme given directly to people was located during data entry, in the published literature or in the trial registry, and the two registered studies comparing intravenous NAD+ with intravenous nicotinamide riboside have posted no results.
The anti-doping position is unresolved rather than permissive. No statement from a national or international anti-doping authority naming NAD+, nicotinamide riboside or nicotinamide mononucleotide was retrievable during data entry, and this file does not infer one in either direction.
The published research does not establish a dose, a route, a schedule, a duration or a formulation for any use of this compound in a person, and no source consulted here does either. Nothing on this page should be read as describing how anything is used.
An assigned nonproprietary name is not an approval. This molecule carries an INN, a USAN and a JAN, which places it among a small minority of the compounds in this category, and none of that constitutes a finding by any authority that it is safe or effective for anything.

Storage and handling

Stability is the specific thing FDA faulted, and it did so twice. In its September 5, 2019 proposed rule evaluating NAD as a bulk drug substance, FDA wrote that NAD "is well characterized physically and chemically, but it degrades substantially when exposed to light, moisture, alkaline pH, or standard room temperatures and would not be stable under ordinary storage conditions absent multiple compensatory measures". FDA recorded the same finding separately for the reduced form, NADH. No numeric shelf life, no in-use period and no reconstituted-solution condition is established by any source located during data entry: there is no pharmacopoeial monograph and no approved product label for this substance, so no body with standing to determine handling conditions has done so. Any storage figure circulating for this compound traces to a supplier page rather than to a determination by anyone. source

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