Post-hoc clinical-trial analysis

Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration

Ajla Hodzic Kuerec et al. · Mechanisms of Ageing and Development · 2024

Evidence type: Secondary human analysis Interpretive weight: LimitedResearch area: NAD response variability
DesignPost-hoc analysis of the randomized double-blind 80-person Yi et al. NMN dose-ranging trial
PopulationGenerally healthy adults aged 40–65 years from the parent trial
Sample80 participants from the parent trial
InterventionParent trial: placebo or NMN 300, 600, or 900 mg/day for 60 days
EndpointsChange in blood NAD concentration; Interindividual variability in NAD response; Associations between NAD change and six-minute walk distance; Associations between NAD change and SF-36

What the publication reported

This paper re-analyzed the 80-person Yi et al. randomized trial to examine how strongly individuals differed in their blood NAD response to 300, 600 or 900 mg/day NMN.

The analysis reported a dose-related average increase in NAD but also very large person-to-person variability. Larger increases in NAD were statistically associated with improvements in six-minute walk distance and SF-36 scores.

These are post-hoc associations from the same trial population, not a new randomized comparison. They can generate hypotheses about response variability but cannot prove that targeting a particular NAD level causes better clinical outcomes.

Key findings

  • Blood NAD response increased with dose on average.
  • Within-group variability in NAD response was large.
  • Greater NAD changes were associated with six-minute walk and SF-36 changes.
  • The paper proposed monitoring NAD as a possible basis for personalized dosing.
  • All data came from the previously published Yi et al. trial rather than a new participant cohort.

What it cannot establish

  • Post-hoc secondary analysis.
  • Not an independent clinical trial or new sample.
  • Associations between NAD change and functional outcomes do not establish causality.
  • Commercial sponsorship and affiliations from the parent study remain relevant.
  • Proposed personalized dosing thresholds require prospective validation.
HealthspanX claim boundary: This analysis does not establish a validated personalized NMN dose or target NAD concentration, and does not independently prove functional benefit.

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