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Human whole-blood NAD+ levels do not vary with age or lifestyle interventions

Maria M Tretowicz, Angelique M L Scantlebery, Bauke V Schomakers, Kaan D Eroğlu, Michel van Weeghel, Vera Spek, Kasper T Vinten, Luc Legon, Evrim Coskun, Fernando Millan-Domingo, Gloria Olaso-Gonzalez, Maria Carmen Gomez-Cabrera, Silvia Montoro-García, Clara Noguera-Navarro, André B P van Kuilenburg, Sofia Moco, Juliette C van Hattum, Harald T Jørstad, Mohammed Benali, Jantine van der Helder, Esmee J M Biersteker, Maheswary Muniandy, Kirsi H Pietiläinen, Eija Pirinen, P Eline Slagboom, Marian Beekman, Joris Deelen, Rubén Zapata-Pérez, Peter J M Weijs, Michael Tieland, Georges E Janssens, Riekelt H Houtkooper
Nature Metabolism 2026 8(6):1282–1290

Bibliography

PubMed
PMID 42135539
DOI
10.1038/s42255-026-01537-5
Funding
Funding included EU Horizon Europe NADIS project 101073251, AGEM Innovation, Academy of Finland and Finnish Diabetes Research Foundation support for the twin-pair NR study, EU FP7/Netherlands cohort infrastructure, Dutch research funding, and additional cohort-specific support. The MEJNES2019 cohort included support from Nestlé Health Science.
Competing interests
The authors declared no competing interests.

Study snapshot

DesignMulti-cohort human observational metabolomics study with analytical validation and lifestyle-intervention cohort comparisons.
ModelSeven independent human cohorts spanning age and lifestyle/intervention contexts; supplemental analyses included NR exposure and assay/pre-analytical validation.
SampleSeven independent human cohorts; cohort-specific sample sizes varied. The study was designed around cross-cohort reproducibility rather than a single intervention sample.
InterventionPrimarily observational across age/lifestyle cohorts; included lifestyle-intervention comparisons and an NR supplementation cohort as a positive control for biological responsiveness.
DurationCross-sectional and cohort-specific longitudinal/intervention components; not an NMN supplementation trial.
EndpointsWhole-blood NAD+ concentration; Association of whole-blood NAD+ with age; Association with lifestyle interventions; Pre-analytical stability and freeze-thaw effects; Hematocrit relationship; Responsiveness to NR supplementation

What the study showed, in plain terms

A common longevity claim is that NAD+ in the blood inevitably falls as people age. This 2026 Nature Metabolism study tested that assumption using a rigorously validated mass-spectrometry method across seven independent human cohorts.

Whole-blood NAD+ remained remarkably stable with age and across lifestyle interventions, while the assay still detected expected changes after nicotinamide riboside supplementation. The result argues that whole-blood NAD+ should not be treated as a simple biomarker or 'aging clock.'

This does not prove that NAD+ is age-stable in every tissue. Human muscle and other tissue studies can show different age associations. The paper therefore supports a tissue-specific model of NAD biology rather than a universal systemic-decline narrative.

Key findings

  • Whole-blood NAD+ was remarkably stable with age across seven independent human cohorts.
  • Whole-blood NAD+ also remained stable across the lifestyle interventions examined.
  • The validated assay detected expected NAD+ changes with NR supplementation, supporting its ability to measure genuine intervention-related shifts.
  • Pre-analytical handling meaningfully affects NAD-related measurements and can contribute to discrepancies between studies.
  • The authors concluded that whole-blood NAD+ is not a useful simple biomarker of aging or lifestyle status.

What this study can and cannot tell us

The conclusion is specific to whole blood and cannot be generalized to skeletal muscle, brain, liver or other tissues where age-associated NAD biology may differ.

The study was not an NMN efficacy trial and does not test whether NMN improves clinical outcomes.

Cross-sectional age comparisons cannot resolve every within-person longitudinal change, although the multi-cohort design and analytical validation substantially strengthen the blood-specific conclusion.

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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