Randomized controlled trial

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Lin Yi et al. · GeroScience · 2023

Evidence type: Human randomized trial Interpretive weight: ModerateResearch area: Dose response, NAD and physical-function measures
DesignRandomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-ranging trial; 60 days
PopulationGenerally healthy adults aged 40–65 years
Sample80 participants; 20 each in placebo, 300 mg, 600 mg and 900 mg NMN groups; all completed
InterventionPlacebo or NMN 300, 600, or 900 mg once daily for 60 days
EndpointsBlood NAD concentration; Safety and tolerability; Six-minute walk distance; Blood biological age estimate; HOMA-IR; SF-36 self-reported health

What the publication reported

This dose-ranging randomized trial assigned 80 healthy middle-aged adults to placebo or 300, 600, or 900 mg/day NMN for 60 days. All participants completed the trial.

Blood NAD increased in all NMN groups, with the largest increases in the 600 and 900 mg groups. The publication also reported greater six-minute-walk and some SF-36 changes in NMN groups, while HOMA-IR did not significantly differ from placebo.

The study provides comparatively strong human pharmacodynamic evidence that the tested NMN preparation can raise blood NAD over 60 days, but the duration was short and several clinical or surrogate efficacy endpoints remain exploratory.

Key findings

  • Blood NAD increased significantly in all three NMN dose groups versus baseline and placebo.
  • Blood NAD response was greatest in the 600 and 900 mg groups.
  • No major safety issue was identified across doses up to 900 mg/day for 60 days.
  • Six-minute walk distance improved more in the NMN groups than placebo in the reported analysis.
  • HOMA-IR did not significantly differ between NMN and placebo at day 60.
  • SF-36 changes favored NMN for most reported comparisons, but these are subjective secondary outcomes.

What it cannot establish

  • Intervention lasted only 60 days.
  • The study was fully commercially funded by companies involved with the test product, and three authors were company employees.
  • Clinical efficacy outcomes were secondary and include subjective or surrogate measures.
  • The population was generally healthy and middle-aged, so disease-treatment and longevity conclusions are not supported.
  • The study does not establish an optimal long-term dose.
HealthspanX claim boundary: This record supports short-term blood-NAD pharmacodynamics for the tested product. It does not establish anti-aging, longevity, disease-treatment, or equivalence with HealthspanX NMN.

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