NAD+ (Nicotinamide Adenine Dinucleotide)

Nicotinamide adenine dinucleotide (NAD+) is a pyridine dinucleotide coenzyme present in every living cell, where it functions both as an electron carrier in oxidation-reduction reactions and as a consumed substrate for a set of enzymes that cleave the bond between its nicotinamide and ribose groups. It is a small molecule of nucleotide origin, not a peptide, and it has been studied in the biochemical literature since the early twentieth century.

This page summarises the published record on NAD+: what it does biochemically, what the preclinical literature has reported, where human data exists and where it does not, and how the material is specified and handled in a laboratory setting. It is not a use guide. Material supplied under our research use policy is not FDA approved and is not for human or animal consumption.

Specifications

Two distinct biochemical roles

The first role is redox cycling. NAD+ accepts a hydride ion to become NADH and is re-oxidised back to NAD+, shuttling electrons through glycolysis, the tricarboxylic acid cycle, fatty acid beta-oxidation and oxidative phosphorylation. In this capacity the molecule is recycled stoichiometrically rather than destroyed, and the quantity that matters is the NAD+/NADH ratio rather than the absolute pool.

The second role is as a consumed substrate. Several enzyme families cleave the nicotinamide-ribosyl bond and use the ADP-ribose moiety, degrading NAD+ in the process. Covarrubias et al. (2021), in a review in Nature Reviews Molecular Cell Biology, described these as the sirtuins (SIRT1 through SIRT7, which remove acyl groups from lysine residues), the poly(ADP-ribose) polymerases (PARPs, active in the DNA damage response), the NAD glycohydrolases CD38 and CD157, and SARM1, an NADase implicated in programmed axon degeneration. Because these enzymes consume rather than recycle their substrate, cellular NAD+ concentration is set by the balance between biosynthetic flux and this degradative demand.

Research history

NAD+ was first described in the early twentieth century as a heat-stable, dialysable fraction of yeast extract required for fermentation, and was subsequently characterised as the nicotinamide-containing cofactor of dehydrogenase reactions. For most of the twentieth century it was studied as a fixed component of intermediary metabolism. The research framing changed after the discovery that sirtuins require NAD+ as a co-substrate, which tied the size of the cellular NAD+ pool to protein acylation state and gene regulation, and made NAD+ availability a variable of interest in ageing biology rather than a constant.

Preclinical findings

Most of the mechanistic literature on NAD+ availability has been generated in rodents and in cultured cells, and much of it tested biosynthetic precursors rather than NAD+ itself.

• Gomes et al. (2013), in a murine model, reported that a decline in nuclear NAD+ with age was associated with accumulation of HIF-1alpha and a specific loss of mitochondrially encoded oxidative phosphorylation subunits, describing this as a pseudohypoxic disruption of nuclear-mitochondrial communication.
• Camacho-Pereira et al. (2016), in mice, reported that expression and activity of the NADase CD38 increased with age and that CD38 was required for the age-related decline in tissue NAD, via a mechanism they attributed in part to SIRT3 regulation. The same work identified CD38 as a principal route of nicotinamide mononucleotide degradation in vivo.
• Zhang et al. (2016) administered the precursor nicotinamide riboside to aged mice and reported effects on muscle, neural and melanocyte stem cell compartments together with induction of the mitochondrial unfolded protein response.
• Mills et al. (2016) conducted a twelve-month administration of nicotinamide mononucleotide to chow-fed C57BL/6N mice during normal ageing and reported changes in age-associated metabolic parameters.

These are animal and cell-culture findings. They characterise NAD+ biology in those models; they do not establish outcomes in humans.

What the human literature does and does not show

Route of delivery is a live methodological question rather than a settled one. Liu et al. (2018), using isotope-tracer flux analysis in mice and in cell lines, reported that nicotinamide riboside and nicotinamide mononucleotide delivered intravenously reached multiple tissues intact, whereas the same compounds given orally were metabolised to nicotinamide in the liver. That work concerns precursors in rodents, but it is the clearest published illustration of why the form and route used in a study constrain what the study can be said to show.

Direct human data on NAD+ itself is sparse. Grant et al. (2019) published a pilot pharmacokinetic study in which the plasma and urine NAD+ metabolome was tracked during and after a six-hour intravenous NAD+ infusion in eleven healthy male volunteers aged 30 to 55, eight of whom received the infusion. The reported result was notably undramatic: no change in plasma NAD+ or in the measured metabolites was detected until after two hours, with increased urinary excretion of NAD+ and methylnicotinamide observed at six hours. That study was a metabolome and pharmacokinetic characterisation. It was not designed to, and did not, evaluate clinical outcomes.

A frequently cited human trial in this area tested a precursor, not NAD+. Yoshino et al. (2021), in Science, reported a ten-week randomised, placebo-controlled study of nicotinamide mononucleotide in postmenopausal women with prediabetes, with insulin-stimulated glucose disposal measured by hyperinsulinaemic-euglycaemic clamp as the primary readout. The reported findings were subsequently contested in a published Comment in the same journal, to which the authors responded. Two points bear on any reading of that trial: it studied NMN rather than NAD+, and its interpretation is disputed in the peer-reviewed record.

Stated plainly: there is no body of adequate, well-controlled human efficacy data for administered NAD+ in any indication.

Analytical considerations

Purity of NAD+ material is conventionally assessed by HPLC with UV detection, with identity confirmed by mass spectrometry. Two variables cause more confusion than any other when comparing certificates of analysis between suppliers. The first is salt form: a vial of the sodium salt contains fewer moles of NAD+ per stated milligram than a vial of the free acid, and a certificate that does not name the form is incomplete. The second is water content, since NAD+ is hygroscopic; Karl Fischer titration or loss-on-drying data allows mass-per-vial to be interpreted correctly. Comparing supplier paperwork on these points is covered in our notes on third-party lab testing.

Handling and stability

NAD+ is hygroscopic and light sensitive in the solid state, and is least stable in aqueous solution at alkaline pH. Solid material is conventionally held at minus 20 degrees C, desiccated and protected from light; vials should be brought to room temperature before opening to avoid condensation onto cold powder. General cold-chain and container guidance is collected under storage, and the arithmetic for converting a stated vial mass and diluent volume into a solution concentration is the same for any solute, so the concentration calculator and the notes on dissolving lyophilised material apply here as they do to peptide material.

Regulatory status

NAD+ is not an FDA-approved drug and has not been approved to treat, prevent, cure or mitigate any condition. FDA has evaluated nicotinamide adenine dinucleotide as a bulk drug substance nominated for use in pharmacy compounding under section 503A of the Federal Food, Drug, and Cosmetic Act, and in a 2019 proposed rule proposed that it not be included on the 503A Bulks List. Material supplied here is offered for laboratory research use only, is not for human or animal consumption, and is not supplied for any diagnostic or therapeutic purpose. See the full research use policy.

How should lyophilised NAD+ be stored?

Solid material is conventionally stored at minus 20 degrees C, desiccated and protected from light. NAD+ takes up atmospheric moisture readily, so the desiccant and the seal matter as much as the temperature.

Does the salt form change how much NAD+ a vial contains?

Yes. The sodium salt has a higher formula weight than the free acid, so an equal mass contains fewer moles of NAD+. A certificate of analysis should state the form explicitly, along with water content, before mass-per-vial figures can be compared between lots or suppliers.

What documentation should accompany research-grade NAD+?

At minimum: an HPLC purity chromatogram with the method stated, mass spectrometric identity confirmation, the salt form, water content, and the lot number tying the paperwork to the physical vial. Our lab testing page explains how to read each of these independently.

Is NAD+ approved by the FDA?

No. It is not an approved drug for any indication. It is supplied for laboratory research use only and is not for human or animal consumption.