Human whole-blood NAD+ levels do not vary with age or lifestyle interventions
Across seven independent human cohorts measured with a validated UHPLC-high-resolution MS method designed to account for real-world analytical variability, whole-blood NAD+ was essentially flat with age and unmoved by lifestyle interventions, while responding as expected to nicotinamide riboside supplementation. The authors conclude this challenges the use of blood NAD+ as a biomarker of ageing or of lifestyle. The methodological implication is that much of the age-related decline reported in the prior literature may reflect assay variability rather than biology.
Evidence
7/10
Moderate Evidence
Sample
—
subjects
Duration
—
study period
Journal
Nature Metabolism
May 2026
Full Abstract
Nicotinamide adenine dinucleotide (NAD+) levels in blood and tissues are widely proposed to decline with age, yet evidence in human blood is inconsistent. Using a rigorously validated ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry system that accounts for real-world analytical variability, the authors quantify NAD+ across seven independent human cohorts. Whole-blood NAD+ levels remain remarkably stable with age and across lifestyle interventions, but change in response to nicotinamide riboside supplementation, as expected. The results challenge the utility of blood NAD+ levels as a biomarker of ageing or lifestyle factors.
Key Findings
- 01
Whole-blood NAD+ did not decline with chronological age across seven independent human cohorts
- 02
Whole-blood NAD+ did not shift in response to lifestyle interventions
- 03
Whole-blood NAD+ did rise with nicotinamide riboside supplementation, confirming assay sensitivity
- 04
Authors conclude blood NAD+ is not a useful biomarker of ageing or lifestyle
- 05
Prior reports of age-related blood NAD+ decline are plausibly attributable to analytical variability
Structured Methods
- Study Design
- Observational Study
- Sample Size
- Not reported
- Study Duration
- Not reported
- Methodology
- Validated ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), applied across seven independent human cohorts, with explicit accounting for real-world pre-analytical and analytical variability.
- Limitations
- Brief Communication format. Whole blood only - does not address tissue or intracellular NAD+, where age-related decline may still occur. Cohorts are observational and the lifestyle interventions vary in type and duration. Does not evaluate clinical outcomes of NAD+ precursor supplementation, only the behaviour of the blood measurement itself.
Citations & References
Maria M. Tretowicz, Angelique M. L. Scantlebery, Bauke V. Schomakers, Kaan D. Eroglu, Michel van Weeghel, Riekelt H. Houtkooper (2026). Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nature Metabolism. https://doi.org/10.1038/s42255-026-01537-5
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