Explainer
How NMN works: NAD and sirtuins
Quick answer
NMN is a vitamin B3 derivative your body can convert into NAD+. NAD+ is a coenzyme that powers hundreds of reactions, including enzymes called sirtuins that help regulate energy use, stress responses, and aspects of cellular maintenance. Human trials consistently show oral NMN can raise blood NAD+. Whether that translates into noticeable changes depends on dose, duration, and the person. This is an explainer, not medical advice.
NAD+ salvage pathway at a glance
| Step | Enzyme | From | To | Notes |
|---|---|---|---|---|
| 1 Salvage | NAMPT | Niacinamide (NAM) | NMN | Often considered rate‑limiting in the salvage route |
| 2 Activation | NMNAT1‑3 | NMN | NAD+ | Occurs in nucleus, cytosol, and mitochondria depending on isoform |
| Alt NR route | NRK1/2 | NR | NMN | NR is another NAD+ precursor that feeds into NMN |
| Use Consumption | Sirtuins, PARPs, CD38 | NAD+ | NAM + products | These enzymes consume NAD+ during their reactions |
In plain English: precursors like NMN and NR help refill the NAD+ pool. Enzymes then use that pool to do work. Balance between production and consumption sets your NAD+ availability.
The key players
NAD+
A coenzyme that shuttles electrons in metabolism and serves as a substrate for enzymes that regulate DNA repair and cell signaling. Cells recycle NAD+ continuously through salvage pathways.
Sirtuins
A family of NAD‑dependent deacylases and ADP‑ribosyltransferases. In humans, SIRT1 to SIRT7 act in the nucleus, cytosol, and mitochondria to influence gene expression, mitochondrial biogenesis, and stress responses. Their activity depends on NAD+ availability.
PARPs and CD38
PARPs use NAD+ during DNA repair and signaling. CD38 is an NAD‑consuming enzyme at the cell surface and in organelles. Higher activity of these enzymes increases NAD+ turnover.
NAMPT and NMNAT
NAMPT converts niacinamide to NMN. NMNAT enzymes convert NMN to NAD+. Together they form the core salvage route that keeps cellular NAD+ supplied.
Where NMN fits in
When you take NMN orally, it contributes to the same pool that cells use to make NAD+. Studies in adults show increases in circulating NAD+ or related metabolites over several weeks of oral NMN. Details of transport and conversion can vary by tissue. The practical takeaway is simple: precursors like NMN support the pool, and the pool powers NAD‑dependent enzymes.
Why NAD+ and sirtuins matter
- Energy metabolism: NAD+/NADH are central in glycolysis, the TCA cycle, and the electron transport chain
- Cell maintenance: sirtuins help regulate mitochondrial function, protein quality control, and aspects of stress resistance
- DNA repair and signaling: PARPs use NAD+ during repair responses, which competes for the same pool
- Circadian rhythms: cellular clocks and NAD+ influence each other, which helps explain why timing and sleep matter for recovery and performance
Practical takeaways
- Inputs and outputs both matter: raising supply with precursors is only half the story. High consumption by PARPs or CD38 can drain the pool
- Consistency over spikes: most human trials use steady daily intakes for 8 to 12 weeks
- Lifestyle amplifiers: sleep, training, and nutrition influence how cells use NAD+. A consistent routine pairs well with a consistent dose
- Effect sizes are modest: expect small changes at most. Track meaningful metrics and reassess after a cycle
Mini glossary
- NAD+ nicotinamide adenine dinucleotide, oxidized form used by enzymes
- NMN nicotinamide mononucleotide, an intermediate on the way to NAD+
- NR nicotinamide riboside, another precursor that converts to NMN
- NAMPT enzyme that converts niacinamide to NMN
- NMNAT enzymes that convert NMN to NAD+
- Sirtuins NAD‑dependent enzymes involved in gene regulation and mitochondrial function
- PARPs DNA repair enzymes that consume NAD+
- CD38 major NAD‑consuming enzyme impacting NAD+ availability
FAQ
- Is NMN the same as NAD+
- No. NMN is a precursor. Cells convert NMN to NAD+, which enzymes then use to do work.
- Do I need resveratrol for sirtuins to work
- No. Sirtuins require NAD+. Resveratrol influences related pathways in models, but human effects are mixed. Focus on consistent, evidence‑based inputs and good sleep, training, and nutrition.
- How fast does NAD+ change after taking NMN
- Trials typically measure changes over 4 to 12 weeks. Day‑to‑day swings are less important than a steady routine over time.
- Will higher NAD+ guarantee better performance
- No. Human outcomes vary and are usually modest. Consider NMN one input among many, not a replacement for training, sleep, or medical care.
Safety basics
Human studies generally report good short‑term tolerability for oral NMN within common study ranges. Long‑term data remain limited. If you are pregnant or nursing, under 18, or on prescription medications that affect blood sugar or blood pressure, talk with your clinician before use. This page is educational, not medical advice.
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