NAD+
The central redox cofactor — and the substrate that sirtuins and PARPs consume.
Mitochondrial & energy · 7 min read · updated 13 Aug 2026
Research use only. The ranges below are what published studies and community protocols report. They are reference material for laboratory research, not medical advice or a recommendation for human or veterinary use.
The compound
NAD+
View- Type
- Coenzyme
- CAS
- 53-84-9
- Formula
- C₂₁H₂₇N₇O₁₄P₂
- Mass
- 663.43 Da
At a glance
- Class
- Pyridine dinucleotide coenzyme
- Full name
- Nicotinamide adenine dinucleotide (oxidised form)
- Molecular weight
- 663.43 Da
- CAS
- 53-84-9
- Charge
- Highly polar — poor passive membrane permeability
- Vial size stocked
- 500 mg
NAD+ is not a peptide and does not behave like one. It is the electron carrier that sits at the centre of catabolism — glycolysis, the TCA cycle and β-oxidation all reduce it to NADH, and the electron transport chain reoxidises it. That recycling role means the cell needs a pool, not a supply.
What made NAD+ a research target is the second job: it is a consumed substrate, not just a carrier. Sirtuins (SIRT1–7) cleave NAD+ to deacetylate their targets. PARP enzymes consume it during DNA repair. CD38, an ectoenzyme that rises with age and inflammation, degrades it outright. Every one of those reactions destroys the molecule, so the pool has to be continuously resynthesised — mainly through the salvage pathway, where NAMPT converts nicotinamide back to NMN and NMNAT completes the loop.
Tissue NAD+ declines with age across multiple species, and CD38 up-regulation is a major driver of that decline. The research question that follows is whether restoring the pool restores the downstream enzymology — and that question is still open.
The permeability problem — read this before designing a protocol
NAD+ carries two phosphate groups and a net negative charge at physiological pH. It does not cross intact cell membranes efficiently by passive diffusion. Most extracellular NAD+ is degraded by ectoenzymes such as CD38 and CD73 into nicotinamide riboside or nicotinamide, which then enter the cell and are rebuilt into NAD+ internally.
This is why much of the field works with precursors — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — rather than with NAD+ itself. Administering NAD+ directly is, in mechanistic terms, largely an indirect way of delivering those precursors plus a transient extracellular signalling load. That is not an argument against the research use of NAD+; it is an argument for describing what it does accurately.
Where it is studied
- Mitochondrial function and the NAD+/NADH ratio as a determinant of oxidative capacity.
- Sirtuin-dependent processes — mitochondrial biogenesis via PGC-1α, and the deacetylation targets downstream of SIRT1 and SIRT3.
- DNA damage response, where PARP1 activation acutely depletes the NAD+ pool.
- Age-associated decline, with CD38 inhibition as an alternative strategy to supplementation.
- Neuroprotection models, where axonal NAD+ depletion via SARM1 is a well-characterised degeneration mechanism.
Route and rate
The single most consistent observation in reported NAD+ administration is that rate matters more than dose. Rapid intravenous infusion produces flushing, chest tightness, nausea and a pressured, uncomfortable sensation that resolves when the rate is reduced. Slow infusion over hours is the standard in reported protocols for that reason. Subcutaneous administration produces the same effect at the injection site instead — stinging is routine, and it scales with concentration and speed of injection.
Storage
- Lyophilised: 2–8 °C, or −20 °C for long storage. Keep dry — the powder is hygroscopic.
- Reconstituted: 2–8 °C and used quickly. Reported practice keeps the window to 7–14 days, shorter than the 28 days typical of peptides.
- Protect from light and from repeated warming; both accelerate degradation.
Cautions
- Infusion-rate reactions — flushing, chest pressure, nausea, cramping — are the defining tolerability issue and are rate-dependent, not dose-dependent.
- Subcutaneous administration commonly stings; concentration reduction is the practical mitigation.
- Because NAD+ is consumed by PARP during DNA repair, any model involving DNA-damaging agents will interact with the pool.
- The precursor question is not settled. Studies showing benefit from NR or NMN do not automatically transfer to administered NAD+, and vice versa.
References & credit
- 1Rajman L, Chwalek K, Sinclair DA — Cell Metabolism 2018 — Review of NAD+ precursors and the therapeutic rationale.
- 2Camacho-Pereira J et al., Cell Metabolism 2016 — CD38 as a driver of age-related NAD+ decline.
- 3Cantó C, Menzies KJ, Auwerx J — Cell Metabolism 2015 — NAD+ metabolism and the control of energy homeostasis.
This article was written in-house. Where a dose range reflects community practice rather than a published trial, the community references we consulted are credited above and the article says which is which.