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NAD⁺ and NR: what we know, and why we built a network

NAD⁺ is one of the most hyped molecules in longevity science. Here's how the body makes and uses it, what human trials of NR actually show, and why 4VIA treats NAD⁺ as a network rather than one molecule.

BY 4VIA04 November 2026
In short
  • NAD⁺ is a molecule every cell uses to turn food into energy and to maintain itself.
  • NR (nicotinamide riboside) reliably raises NAD⁺ in the blood. That's well established in humans.
  • What isn't established: that raising it makes healthy people feel better, age more slowly or live longer. Results on real outcomes are mixed.
  • NAD⁺ is made, used and recycled through several connected routes, with vitamins B2, B6 and B3 involved along the way. That's why 4VIA approaches it as a network: NR alongside niacin, B2, B6, CoQ10, resveratrol and PQQ.
  • In GB, NR chloride is an authorised novel food for supplements, up to 300 mg a day for adults. NMN isn't authorised.

Every few years, biology produces a molecule that captures the public imagination. For the last decade, it's been NAD⁺.

The story is seductive. NAD⁺ helps power your cells. Levels fall with age. Top them up, and perhaps you turn back the clock. Some of that story is true. Some of it is a leap. The interesting part is telling them apart.

What NAD⁺ does

NAD⁺ (nicotinamide adenine dinucleotide) is a helper molecule in every cell. It shuttles energy in metabolism, and it fuels enzymes involved in DNA repair and cellular maintenance. Without it, life stops. That much isn't controversial.

Does it really fall with age?

In some tissues, it seems so. A small brain-imaging study found lower NAD⁺ in older adults.¹ But that study had 17 people and measured one point in time. Different tissues behave differently, and measurements vary by method. You'll often see a confident figure like "half by middle age". The evidence doesn't support one universal number.

What NR does in humans

NR is a form of vitamin B3 that the body converts into NAD⁺. On this, the human evidence is strong: in randomised trials, NR raises NAD⁺ in the blood in a dose-dependent way, from 100 to 1,000 mg a day over eight weeks.² It was well tolerated in the short term.²˒³

The measurement and the leap
Shown in human trials
NR → higher blood NAD⁺
Normal biology
NAD⁺ participates in energy metabolism and cell maintenance.
Not established
Higher blood NAD⁺ → longer human life
A change in a blood marker is not the same as a proven health outcome.

Does it change anything you'd notice?

This is where the evidence becomes genuinely mixed.

  • No effect: in men with obesity, 2,000 mg a day for 12 weeks didn't improve insulin sensitivity.⁴ In long-COVID, 2,000 mg a day raised NAD⁺ but didn't improve fatigue, cognition, sleep or mood compared with placebo.⁵
  • A modest signal: in people with peripheral artery disease, 1,000 mg a day for six months improved six-minute walking distance by about 18 metres.⁶ That's one small trial in a specific disease, not healthy adults.

The honest summary: NR changes the marker; it hasn't yet reliably changed outcomes. And no trial has shown that it extends human life.

NAD⁺ is a network, not a single molecule

Most NAD⁺ marketing draws a straight line: take precursor, get NAD⁺. The body's version is a network with several entrances, several consumers and constant recycling.

Three ways in.

  • From scratch, out of tryptophan, an amino acid in protein. This long route depends on enzymes that use vitamin B2 and vitamin B6 as cofactors.
  • From niacin (nicotinic acid), a form of vitamin B3.
  • The salvage route, which recycles nicotinamide, and takes in NR and NMN. Most of the body's daily NAD⁺ comes from recycling rather than new supply.

Constant use. NAD⁺ isn't just "used up" making energy. Families of enzymes consume it as they work: sirtuins, involved in how cells respond to stress and nutrients; PARPs, involved in DNA repair; and CD38, an enzyme whose activity rises with age and inflammation and is one proposed reason levels fall.¹⁰

Partners in the same pathways. In mitochondria, NADH (the loaded form of NAD⁺) hands its energy to the electron transport chain, where coenzyme Q10 carries it onward. Resveratrol and PQQ are studied in the lab for their links to sirtuin and mitochondrial pathways; human evidence for both is still limited.

Many inputs. Constant recycling.
Routes in
Tryptophan pathway, with B2/B6 cofactors
Niacin pathway
Salvage route, including NR
NAD⁺
Used and recycled continually.

NADH transfers energy into the mitochondrial electron transport chain, where CoQ10 carries electrons onward.
Consumers
Sirtuins
PARPs
CD38
A simplified pathway map; the presence of a nutrient in a pathway does not establish a benefit from supplementing it.

How 4VIA approaches NAD⁺

So we didn't build around one NAD⁺ ingredient at a high dose. We built an NAD⁺ network:

  • NR, 125 mg, microencapsulated to protect it in the powder, within its GB authorised use.
  • Niacin, 20 mg NE (125% NRV), another form of B3. Niacin contributes to normal energy-yielding metabolism.
  • Vitamins B2 and B6, the cofactors in the body's own route from tryptophan.
  • CoQ10 (50 mg), trans-resveratrol and PQQ (10 mg), partners studied in the same pathways.

NR sits at the centre because it's the NAD⁺ precursor with the strongest human evidence: in randomised trials, it consistently raises NAD⁺ in the blood. The rest of the network reflects how the biology works: many inputs, many uses, one connected system.

Why NR rather than NMN? It has the longer human research record, it's authorised in GB, and it enters cells without being converted first. We explain all three in NR vs NMN: why we chose NR.

What we still don't know

  • Which tissues matter, and whether blood levels reflect them.
  • Who responds: older people, people with low levels, people with specific conditions?
  • Whether any benefit lasts over years, and whether it's safe over decades.

References

  1. Zhu XH et al. PNAS. 2015;112:2876–2881. doi:10.1073/pnas.1417921112
  2. Conze D et al. Sci Rep. 2019;9:9772
  3. Martens CR et al. Nat Commun. 2018;9:1286. doi:10.1038/s41467-018-03421-7
  4. Dollerup OL et al. Am J Clin Nutr. 2018;108:343–353
  5. Wu CY et al. EClinicalMedicine. 2025;103633
  6. McDermott MM et al. Nat Commun. 2024;15. doi:10.1038/s41467-024-49092-5
  7. Yoshino M et al. Science. 2021;372:1224–1229
  8. EFSA J. 2019;17:e05775; Reg. (EU) 2020/16; FSA novel-food register, checked 29 Oct 2026
  9. FSA application RP-2116, checked 29 Oct 2026
  10. Covarrubias AJ et al. NAD⁺ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 2021;22:119–141. doi:10.1038/s41580-020-00313-x

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