NAD+ (nicotinamide adenine dinucleotide) is present in every one of our cells. It helps turn food into energy and supplies enzymes that repair DNA and regulate metabolism. Since mouse studies associated its decline with ageing, it has become a flagship molecule in longevity research. Here is what NAD+ is, what it does, how the body makes it and what is actually known about its age-related decline in humans.
Key takeaways
- NAD+ is a coenzyme made from vitamin B3 and tryptophan; over 400 enzymes need it.
- It transports electrons for energy production and supplies sirtuins, PARPs and CD38, which consume it.
- In mice, levels fall with age in many tissues. In humans, decline is tissue-dependent and remains debated in blood.
- Precursors can raise NAD+, but human health benefits remain to be demonstrated.
What is NAD+?
NAD+ is a coenzyme: a small molecule that certain enzymes need to function. Its name describes its structure: two nucleotides connected by their phosphate groups, one bearing adenine and the other nicotinamide, a form of vitamin B3.
It was described in 1906 as a component accelerating yeast fermentation. Over 400 enzymes are now known to depend on it, more than any other vitamin-derived coenzyme.
NAD+, NADH and NADP+: one family
NAD+ is the oxidised form, ready to accept electrons. Receiving them turns it into reduced NADH, which passes them onward in the cell. This continuous exchange is detailed in the difference between NAD+ and NADH.
Around 10% of cellular NAD+ is also transformed into NADP+. Reduced NADPH helps make cholesterol and fatty acids and supports antioxidant defences, notably recycling glutathione, the antioxidant our cells produce.
What does NAD+ do in cells?
It has two very different roles: carrying electrons without destruction and supplying enzymes that consume it.
Producing energy from food
When cells break down glucose, fatty acids or amino acids, NAD+ accepts electrons, becoming NADH. NADH delivers them to the mitochondrial respiratory chain to make ATP, cellular energy currency. NAD+ is regenerated: recycled, not consumed, in this role.
This is reflected in a vitamin B3 authorised claim: “niacin contributes to normal energy-yielding metabolism”.
Supplying sirtuins
Sirtuins are seven enzymes removing small chemical groups from proteins, changing their activity. They regulate metabolism, stress responses and gene expression. Each reaction consumes one NAD+ and releases nicotinamide.
Because sirtuins depend on the available NAD+, they link the cell's energy state to its function. This explains the interest in other molecules associated with sirtuins, such as resveratrol, between myths and realities. A qualification is needed: several sirtuins are already saturated at usual NAD+ concentrations and do not necessarily respond to variations in those concentrations.
Repairing DNA with PARPs
PARPs (poly-ADP-ribose polymerases) detect DNA breaks and attach ADP-ribose chains cut from NAD+ to recruit repair enzymes. PARP1 alone accounts for around 90% of this family's NAD+ use.
With major damage, PARPs may take up to 90% of cellular NAD+ consumption, leaving less for sirtuins: the enzyme families compete.
CD38: the major consumer
CD38 is present on many cell surfaces, particularly immune cells. It breaks down NAD+ to produce signalling messengers. In mice, activity rises with age and animals lacking it do not experience age-related NAD+ decline.
Another mouse study showed senescent cells releasing inflammatory molecules cause liver and abdominal-fat macrophages to produce more CD38. These tissues' NAD+ then decreases.
| Enzymes | Main role | Effect on NAD+ |
|---|---|---|
| Dehydrogenases | Energy production | Converted to NADH, then recycled |
| Sirtuins | Metabolism and gene regulation | Consumed, releases nicotinamide |
| PARPs | DNA repair | Consumed, sometimes extensively |
| CD38 and related enzymes | Signalling, immunity | Broken down |
| NAD kinases | NADP+ synthesis | Converted (around 10%) |
How does the body make NAD+?
The body does not stockpile NAD+: it makes and recycles it continuously through three pathways.
- The de novo pathway starts from tryptophan, an amino acid supplied by proteins. It requires other nutrients: without enough vitamin B2, vitamin B6 or iron, conversion decreases. As a guide, around 60mg of tryptophan is needed to obtain the equivalent of 1mg of niacin.
- The Preiss–Handler pathway starts from nicotinic acid, a vitamin B3 form.
- The salvage pathway recycles nicotinamide released by sirtuins, PARPs and CD38. It also accepts nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Its rate-limiting enzyme is NAMPT.
The salvage pathway supplies the bulk of NAD+: most is recycled rather than made from scratch. NR also uses this pathway. It is the form used in Hexagon® NAD+ Nicotinamide Riboside Chloride 300mg, taken as one capsule per day.
NAD+ is compartmentalised: mitochondrial stores are largely separate from cytoplasm and nucleus. Approaches and precursors raising it are reviewed in our guide to increasing NAD+.
Why does NAD+ decline with age?
The NAD+ level results from a balance between production and consumption. Research, mostly conducted in animals, identifies two mechanisms that add together.
- Greater consumption: accumulated DNA damage activates PARPs, while low-grade chronic inflammation raises CD38.
- Lower production: in human muscle, NAMPT, the key recycling enzyme, is around 35% lower at seventy than twenty.
A study of 49 human skin samples from birth to age 77 found increasing PARP activity in men alongside lower NAD+. This is consistent with, but does not prove, this scenario.
Even in mice, decline is uneven. The most comprehensive young-versus-old comparison found it in only ten of 21 tissues: around 40 to 50% lower in fat and part of the intestine, 10 to 20% in muscle, liver or kidney, with no heart or brain change.
What human measurements show
Human measurements are rare, in small groups, comparing younger and older people at one time without following the same individuals. Results depend on tissue.
| Tissue | Study | Result |
|---|---|---|
| Skin | 49 people aged 0 to 77 | Lower NAD+ with age in men and women |
| Brain | Healthy volunteers, magnetic resonance | NAD+ decreases, NADH increases with age |
| Muscle | Young and old, active or frail | Lower NAD+ in older people, particularly inactive |
| Whole blood | 1,518 adults | Slight decline in men only |
| Whole blood | 7 cohorts, validated method | No age-related variation |
In the brain, the decline between ages 20 and 60 is estimated at 10 to 20%. In muscle, trained older people have NAD+ levels close to those of younger people, and levels track the number of daily steps. In blood, a Chinese study finds a modest decline in men, significant after age 60, and absent in women. A 2026 analysis of seven cohorts finds no age effect, although blood NAD+ does rise with nicotinamide riboside.
The reference review concludes age-related NAD+ changes remain poorly characterised in humans, requiring much larger studies, ideally following people for years.
NAD+ and longevity: established facts and hypotheses
In mice, raising NAD+ with nicotinamide riboside improves mitochondrial and muscle stem-cell function, and one study observed a longer lifespan. In humans, two points are established: NAD+ is involved in vital functions, and precursors increase the NAD+ measured in blood.
The rest remains a subject for research. A 2021 review stresses that we still need to understand how to effectively restore NAD+ during ageing, whether this is safe and whether it benefits older people. Trials with nicotinamide riboside are discussed in a dedicated article.
- Cause or consequence? Low NAD+ may reflect inactivity or disease rather than age itself, as muscle data suggest.
- More is not always better. In the laboratory, NAD+ also fuels senescent-cell inflammatory signals. Authors call for precision when raising it.
- No human lifespan data. No study shows raising NAD+ extends human life.
Frequently asked questions
What does the “+” in NAD+ mean?
It recalls the positive charge on nicotinamide's nitrogen in the electron-accepting oxidised form; the whole molecule remains negatively charged due to phosphates. “NAD” describes both NAD+ and NADH, “NAD+” only the oxidised form.
Is NAD+ a vitamin?
No. It is a coenzyme made by the body. B3 (niacin) is the vitamin: with tryptophan, it supplies raw materials and must come from diet.
Is NAD+ found in food?
Yes: meat, poultry and fish mainly supply B3 as NAD and NADP. But these are converted to nicotinamide in the intestine before absorption. We do not eat NAD+ “unchanged”: we supply building blocks.
At what age does NAD+ start falling?
No study allows us to set an age in humans: no research has followed the same people over decades. The dramatic figures circulating online are not based on robust human measurements.
Is NAD+ linked to cancer?
This is a subject for research. Tumour cells also need NAD+, and certain cancer treatments block PARPs, enzymes that use it. Long-term data on precursors are lacking: if you have a history of cancer, discuss it with your doctor before any supplementation.
Does NAD+ have an authorised health claim?
No. In the EU, NAD+, NADH and NR have no specific claims. Only niacin (B3) has claims such as “niacin contributes to the reduction of tiredness and fatigue”, for products supplying sufficient amounts.
Conclusion
NAD+ is essential: it drives energy production and supplies sirtuins, PARPs and CD38. The body makes it from B3 and tryptophan and continuously recycles it. Age-related decline is documented in some animal tissues and even more nuanced in humans: real in skin or brain, debated in blood, perhaps as related to lifestyle as years. Raising NAD+ is possible, but human health benefits remain unproved.
Sources
- Xie N et al. (2020). NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy, 5(1), 227. doi:10.1038/s41392-020-00311-7
- NIH Office of Dietary Supplements (2022). Niacin – Fact Sheet for Health Professionals. ods.od.nih.gov
- Regulation (EU) No 432/2012 establishing a list of permitted health claims made on foods. eur-lex.europa.eu
- Covarrubias AJ, Perrone R, Grozio A, Verdin E (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119-141. doi:10.1038/s41580-020-00313-x
- Camacho-Pereira J et al. (2016). CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metabolism, 23(6), 1127-1139. doi:10.1016/j.cmet.2016.05.006
- Covarrubias AJ et al. (2020). Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nature Metabolism, 2(11), 1265-1283. doi:10.1038/s42255-020-00305-3
- Massudi H et al. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One, 7(7), e42357. doi:10.1371/journal.pone.0042357
- Zhu XH et al. (2015). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences, 112(9), 2876-2881. doi:10.1073/pnas.1417921112
- Janssens GE et al. (2022). Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nature Aging, 2(3), 254-263. doi:10.1038/s43587-022-00174-3
- Yang F et al. (2022). Association of Human Whole Blood NAD+ Contents With Aging. Frontiers in Endocrinology, 13, 829658. doi:10.3389/fendo.2022.829658
- Tretowicz MM et al. (2026). Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nature Metabolism, 8(6), 1282-1290. doi:10.1038/s42255-026-01537-5
- Peluso A, Damgaard MV, Mori MAS, Treebak JT (2021). Age-Dependent Decline of NAD+ – Universal Truth or Confounded Consensus? Nutrients, 14(1), 101. doi:10.3390/nu14010101
- Zhang H et al. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443. doi:10.1126/science.aaf2693
- Nacarelli T et al. (2019). NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nature Cell Biology, 21(3), 397-407. doi:10.1038/s41556-019-0287-4
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