NAD+ – Peptide Lexicon

NAD+

beta-NAD+ · Coenzyme I · DPN · Nadide

Clinical (early phases)Anti-AgingRecoveryCognition· Longevity / Cofactor

NAD+ (nicotinamide adenine dinucleotide, CAS 53-84-9) is an endogenous dinucleotide coenzyme and not a peptide. It serves as the central redox cofactor of energy metabolism and, at the same time, as a consumed substrate for NAD+-dependent signalling enzymes such as sirtuins, PARPs and CD38. In research it appears mainly in work on ageing metabolism, mitochondrial function and neurodegeneration, with the bulk of human data covering precursor molecules such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) rather than NAD+ itself.

Published on Aug 11, 2026

Mechanism of action

NAD+ is the central electron acceptor of catabolic metabolism: in the NAD+/NADH redox cycle it accepts reducing equivalents from glycolysis, beta-oxidation and the citric acid cycle and releases them again at mitochondrial Complex I of the respiratory chain. Beyond redox chemistry, NAD+ is consumed by signalling enzymes. Sirtuins (SIRT1 to SIRT7, NAD+-dependent class III deacylases, with additional enzymatic activities in some family members) cleave off nicotinamide during catalysis and modulate PGC-1alpha-, FOXO- and p53-dependent programmes; PARP1 uses NAD+ for poly-ADP-ribosylation in the DNA damage response; the ectoenzymes CD38 and CD157 as well as SARM1 hydrolyse NAD+ and lower the cellular pool. The pool is replenished mainly through the salvage pathway (NAMPT, NMNAT1 to NMNAT3, starting from nicotinamide, NR and NMN) and de novo from tryptophan via the kynurenine pathway. This compartmentalisation is why the literature does not equate extracellular NAD+ exposure with a direct rise in the intracellular pool.

State of evidence

The mechanistic basis is broad: in vitro work and rodent models describe an age-associated decline in tissue NAD+ and metabolic effects of raising the pool, for example through CD38 inhibition. In humans, however, controlled data mostly cover the precursors NR and NMN rather than NAD+ itself; the NADPARK trial was a randomised, double-blind phase 1 study of NR in Parkinson's disease, designed for safety, target engagement and feasibility rather than clinical efficacy. For systemically administered NAD+ there is one small open-label pilot investigation of the plasma and urine NAD+ metabolome during a six-hour infusion, with a very small sample size (eight participants in the infusion arm, three in a saline control arm) and no blinding. None of the sources cited here reports a published plasma half-life for systemically administered NAD+; the figure of roughly 1.5 hours carried in the peptide calculator is an estimate without a documented primary reference. Cellular uptake and degradation routes of extracellular NAD+, dose-response relationships and long-term data remain open. There are no phase 3 outcome data and no marketing authorisation for NAD+ as a medicine. Precursor and NAD+ literature are not interchangeable.

Storage and handling

As is standard for lyophilised research material: store cool, dry and protected from light, keeping the container closed. After reconstitution, refrigerated storage and use limited to a few days are described, and repeated freeze-thaw cycles are avoided. These are generic handling notes, not product-specific stability data.

Questions about the research

What is NAD+ studied for in research?: NAD+ is studied as a redox cofactor and as a substrate of NAD+-consuming enzymes, mainly in the context of mitochondrial function, ageing metabolism, the DNA damage response and neurodegeneration. A recurring theme is the age-associated decline of the NAD+ pool seen in tissue models and the question of whether and how it can be influenced. These are mechanistic questions and say nothing about clinical benefit.
What is the state of the evidence on NAD+?: The preclinical literature is extensive, whereas human data are thin and largely indirect: controlled studies mostly involve the precursors NR and NMN, such as a randomised phase 1 trial of NR. For systemically administered NAD+ itself there is essentially one small, open-label pilot investigation of the plasma and urine metabolome during an infusion. No robust efficacy or safety conclusions follow from this, and precursor data must not be transferred to NAD+.

Sources

Rajman, Chwalek, Sinclair, Cell Metab 2018DOI: 10.1016/j.cmet.2018.02.011PMID: 29514064
Yoshino, Baur, Imai, Cell Metab 2018DOI: 10.1016/j.cmet.2017.11.002PMID: 29249689
Brakedal et al., Cell Metab 2022 (NADPARK)DOI: 10.1016/j.cmet.2022.02.001PMID: 35235774
Tarrago et al., Cell Metab 2018DOI: 10.1016/j.cmet.2018.03.016PMID: 29719225
Grant et al., Front Aging Neurosci 2019DOI: 10.3389/fnagi.2019.00257PMID: 31572171

NAD+

beta-NAD+ · Coenzyme I · DPN · Nadide

Clinical (early phases)Anti-AgingRecoveryCognition· Longevity / Cofactor

Published on Aug 11, 2026

Mechanism of action

State of evidence

Storage and handling

Questions about the research

What is NAD+ studied for in research?

NAD+ is studied as a redox cofactor and as a substrate of NAD+-consuming enzymes, mainly in the context of mitochondrial function, ageing metabolism, the DNA damage response and neurodegeneration. A recurring theme is the age-associated decline of the NAD+ pool seen in tissue models and the question of whether and how it can be influenced. These are mechanistic questions and say nothing about clinical benefit.

What is the state of the evidence on NAD+?

The preclinical literature is extensive, whereas human data are thin and largely indirect: controlled studies mostly involve the precursors NR and NMN, such as a randomised phase 1 trial of NR. For systemically administered NAD+ itself there is essentially one small, open-label pilot investigation of the plasma and urine metabolome during an infusion. No robust efficacy or safety conclusions follow from this, and precursor data must not be transferred to NAD+.