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The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation

Haakon Berven, Magnus Svensen, Heidi Eikeland, Nora Tvedten, Erika V Sheard, Solveig Amdahl Af Geijerstam, Mona Søgnen, Adrian McCann, Lena Arnsten, Ove Årseth, Vivian Skjeie, Arve Hjellbrekke, Geir-Olve Skeie, Yamila N Torres Cleuren, Gonzalo S Nido, Kristoffer Haugarvoll, Frank Riemer, Charalampos Tzoulis, Christian Dölle
iScience 2026 29(3):114764

Bibliography

PubMed
PMID 41858901
PubMed Central
PMC12996706
DOI
10.1016/j.isci.2026.114764
Funding
The NAD-brain study lists support from the Norwegian Parkinson’s Disease Association, the Research Council of Norway (including Neuro-SysMed and KOMMERSFORSK), and the Regional Health Authority of Western Norway.
Competing interests
Charalampos Tzoulis and Christian Dölle are listed as inventors on patent applications relating to nicotinamide riboside for Parkinson’s disease and related disorders, filed by VIS on behalf of Haukeland University Hospital.

Study snapshot

DesignSingle-center phase I open-label pharmacokinetic trial with three stages. The key direct comparison was a randomized crossover in six healthy adults receiving NR and NMN; a later parallel stage studied longer NR exposure.
ModelStage 1: six healthy adults (3 women, 3 men). Stage 2: six healthy adults and six people with Parkinson’s disease for extended NR exposure.
SampleDirect NR-vs-NMN crossover: n=6 healthy adults; overall trial also included a one-person pilot and a 12-person extended NR stage.
InterventionStage 1: 600 mg NR twice daily or 600 mg NMN twice daily (1,200 mg/day) for 8 days, with washout and crossover. Stage 2: 600 mg NR twice daily for 4 weeks.
Duration8 days per precursor in the direct crossover stage; 4 weeks in the extended NR stage, with washout follow-up.
EndpointsWhole-blood total NAD; Cerebral total NAD by 31P-MRS; NAD+ and NADH; NAD metabolome; Washout kinetics; Interindividual response; Tolerability

What the study showed, in plain terms

This 2026 phase I study is one of the first direct human comparisons of NMN and nicotinamide riboside (NR). Six healthy adults completed randomized crossover periods with 1,200 mg/day of each precursor for eight days.

Both precursors increased whole-blood NAD, but NR produced a substantially larger short-term blood total-NAD increase in this tiny crossover: about 161% above baseline on day 8 versus about 69% with NMN. Neither precursor significantly increased measured cerebral total NAD over the eight-day crossover period.

The study also found slow blood-NAD kinetics and marked person-to-person variation. Because the direct comparison involved only six people, was open label, and measured biomarkers rather than health outcomes, it should be treated as exploratory rather than as proof that NR is clinically superior to NMN.

Key findings

  • In six healthy adults, 1,200 mg/day NR increased mean whole-blood total NAD from 27.3 to 70.5 μM by day 8, while 1,200 mg/day NMN increased it from 31.8 to 53.7 μM.
  • The authors reported an approximately 2.3-fold larger blood total-NAD increase with NR than NMN over the eight-day crossover, remaining significant after molecular-weight adjustment.
  • Neither NR nor NMN significantly changed cerebral total NAD during the eight-day direct comparison.
  • Blood NAD declined slowly after stopping supplementation, with an estimated elevated-NAD half-life of roughly six days.
  • Both NR and NMN were well tolerated in the direct-comparison stage, with no moderate or severe adverse events reported.
  • The study showed major interindividual variability in NAD responses.

What this study can and cannot tell us

The head-to-head comparison involved only six healthy adults, making effect estimates highly imprecise and vulnerable to chance and participant-specific effects despite the crossover design.

The trial was open label and compared total blood NAD over eight days, which is not necessarily the same estimand or duration as the larger 2026 Nature Metabolism comparison that found similar baseline whole-blood NAD+ increases after 14 days.

The study measured pharmacokinetics and biomarkers, not clinical outcomes such as energy, disease risk, physical performance, cognition or longevity.

NR and NMN products, capsule burden and other protocol details differed; the authors themselves called for harmonized head-to-head studies.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology