NAD+
NAD+ (nicotinamide adenine dinucleotide) is not a peptide; it is a dinucleotide coenzyme essential for redox metabolism and a substrate for sirtuins, PARPs and CD38. It is studied in aging and metabolic research.
Overview
NAD+ is not a peptide. It is a dinucleotide coenzyme made of two nucleotides, one containing nicotinamide and one containing adenine, joined through their phosphate groups. It is included on PeptideWiki because it is frequently discussed alongside research peptides. NAD+ and its reduced form NADH carry electrons in hundreds of metabolic reactions, including glycolysis, the citric acid cycle and oxidative phosphorylation.
Beyond its redox role, NAD+ is consumed as a substrate by enzymes including sirtuins, poly(ADP-ribose) polymerases (PARPs) and the NAD+-hydrolyzing enzyme CD38. Studies in animals and humans have reported that NAD+ levels decline in some tissues with age, which has driven research into whether restoring NAD+ affects age-related changes. Much of this research uses precursors such as nicotinamide riboside and nicotinamide mononucleotide rather than NAD+ itself. Human evidence on clinical outcomes remains limited.
Structure
NAD+ is a dinucleotide, not a peptide, and contains no amino acids. It consists of a nicotinamide ribonucleotide and an adenosine monophosphate joined by a pyrophosphate bridge. The positively charged nicotinamide ring is the site of redox chemistry: it accepts a hydride to form NADH. A phosphorylated derivative, NADP+, and its reduced form NADPH serve mainly in biosynthetic and antioxidant reactions. Commercial NAD+ is typically supplied as the free acid or as a sodium salt.
Mechanism
NAD+ acts in two broad ways. As a redox coenzyme, it accepts electrons in catabolic reactions to become NADH, which then donates electrons to the mitochondrial electron transport chain to support ATP production; this cycling does not consume NAD+. As a substrate, NAD+ is cleaved by sirtuins (protein deacylases involved in metabolic and stress signaling), PARPs (involved in DNA repair) and CD38 and related enzymes, releasing nicotinamide. Cells replenish NAD+ through salvage pathways from nicotinamide and from precursors such as nicotinamide riboside and nicotinamide mononucleotide, and through de novo synthesis from tryptophan.
Research
NAD+ decline in aging models
Rodent studies have reported lower NAD+ levels in several tissues with age, and raising NAD+ with precursors improved measures of mitochondrial function and metabolism in aged animals. Increased CD38 activity has been proposed as one driver of age-related decline. These are mainly animal findings, and the extent and consequences of NAD+ decline in human tissues are still being studied. Measurement methods also vary between studies.
Precursor trials in humans
Randomized trials of nicotinamide riboside and nicotinamide mononucleotide in people have shown that these precursors can raise blood NAD+ or related metabolites. Effects on clinical or functional outcomes such as insulin sensitivity or muscle function have been small or inconsistent across trials. These studies concern precursors, not NAD+ itself. Trials have generally been short, with small sample sizes and varied populations.
Direct NAD+ administration
Studies of NAD+ given directly to people are few and small, and questions remain about how much extracellular NAD+ enters cells intact versus being broken down into precursors first. Pharmacokinetic studies have been limited. Human evidence on direct NAD+ administration is therefore sparse. Dedicated studies of tissue uptake and metabolism in people are needed. Most of the evidence used to discuss NAD+ supplementation comes from precursor trials rather than from NAD+ itself.
Sirtuins, PARPs and DNA repair
Mechanistic studies in cells and animals link NAD+ availability to sirtuin activity and PARP-mediated DNA repair. These relationships are well established at the biochemical level, but how much changes in NAD+ supply alter these processes in human tissues under normal conditions is an active research question. Competition among NAD+-consuming enzymes for a limited NAD+ pool is one hypothesis being explored in cell and animal models.
Regulatory status
NAD+ is not FDA-approved as a drug for any specific indication. Precursors such as nicotinamide riboside are sold as dietary supplement ingredients in the United States, and the regulatory status of nicotinamide mononucleotide as a supplement has been subject to FDA review; check current status. Compounding status should be checked against current FDA lists. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
Because NAD+ is a small-molecule coenzyme rather than a peptide, its certificate of analysis should report identity by mass spectrometry or comparison with a reference standard, purity by HPLC with UV detection, and water content. Key impurities and degradation products include nicotinamide, ADP-ribose, adenosine diphosphate and NADH; the certificate should confirm that the material is the oxidized form (NAD+) rather than NADH or NADP+. The salt form (free acid versus sodium salt) should be stated, since it affects content per milligram.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store NAD+ powder sealed at -20 °C, protected from light and moisture; it is hygroscopic. NAD+ is relatively stable in mildly acidic solution but degrades in basic conditions and at higher temperatures, releasing nicotinamide. NADH, by contrast, is more stable in basic solution and unstable in acid. Prepare solutions close to use, keep them cold, and avoid repeated freeze-thaw cycles.
Download the NAD+ data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention NAD+ in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
Is NAD+ a peptide?
No. NAD+ is a dinucleotide coenzyme made of two nucleotides joined by phosphate groups; it contains no amino acids. It appears on PeptideWiki because it is often discussed in the same research contexts as peptides, particularly in aging and mitochondrial research, and because laboratories handling peptides often handle it as well.
What is the difference between NAD+ and NADH?
NAD+ is the oxidized form of the coenzyme and NADH is the reduced form. In metabolism, NAD+ accepts electrons, becoming NADH, and NADH donates them to the electron transport chain, regenerating NAD+. The ratio of NAD+ to NADH reflects cellular redox state. The two forms also differ in chemical stability: NAD+ is more stable in mild acid, NADH in mild base.
What are NR and NMN?
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are NAD+ precursors, molecules that cells convert into NAD+ through the salvage pathway. They have been studied in randomized human trials, which show they can raise blood NAD+ levels, while effects on clinical outcomes have been modest or inconsistent. Their regulatory status as supplements should be checked.
Related compounds
- 5-Amino-1MQ
5-Amino-1MQ is not a peptide; it is a small-molecule quaternary quinolinium compound that inhibits the enzyme nicotinamide N-methyltransferase (NNMT). It has been studied in cell and rodent models of obesity and metabolism.
- MOTS-c
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene, described in 2015 as a regulator of metabolic homeostasis. Research is mainly in cell and rodent models, with limited human data.
- SS-31 (elamipretide)
SS-31, known as elamipretide, is a synthetic mitochondria-targeted tetrapeptide that binds the inner-membrane lipid cardiolipin. It received FDA accelerated approval in September 2025 as Forzinity for Barth syndrome.
- Glutathione
Glutathione is a tripeptide (γ-Glu-Cys-Gly) found in nearly all cells, where it acts as a major antioxidant and redox buffer. Its glutamate is linked through the side-chain gamma carboxyl, an unusual, non-standard peptide bond.
References
- PubMed: all indexed literature on NAD+
- ClinicalTrials.gov: registered studies mentioning NAD+
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