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NAD+ precursors (nicotinamide riboside and nicotinamide mononucleotide) and mental fatigue: grade C

Limited evidence. Direction: No effect.

C LimitedSubjective outcome only

Educational guidance, not medical advice

Why this grade

Rubric condition met: A network meta-analysis of 27 studies is null for perceived fatigue, but it mixes precursors and clinical cohorts, so not N under the rubric; one RCT found drowsiness improved with placebo as well

The 2026 network meta-analysis of 27 studies (1,599 participants) found that no NAD+ precursor significantly improved perceived fatigue. In the 12-week trial in 108 older Japanese adults, drowsiness improved within both afternoon groups, including placebo; the authors reported a significant interaction and concluded that afternoon NMN reduced drowsiness. Because the pooled studies mix NR, NMN, NADH and nicotinamide and include clinical cohorts, the proposal is C with direction none rather than N.

How we grade evidence

Studies this grade rests on

EffectMixedNo effectSize shows participants (n)202020252030Meta-analysisRCTGao 2026, 2026: meta-analysis, n = 1,599, result not recordedKim 2022, 2022: RCT, n = 108, result not recorded
each study this grade rests on, by publication year and design. Solid: effect versus the comparator; half-filled: mixed; hollow: no effect; dashed: result not recorded yet. Larger marks had more participants.
Show the numbers
StudyYearDesignParticipantsResult
Kim 20222022RCT108result not recorded
Gao 20262026meta-analysis1599result not recorded

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study.

Kim M, Seol J, Sato T. Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study Nutrients, 2022. PMID 35215405

Result not recorded
Design
Randomized, double-blind, placebo-controlled trial, 12 weeks, four groups
Sample
n = 108
Population
Older Japanese adults
Funding
not stated in the PubMed or Crossref record; full text not read

Domain-specific effects of NAD(+) precursors on fatigue and functional performance: a systematic review and network meta-analysis.

Gao Y, Li S, Guan J. Domain-specific effects of NAD(+) precursors on fatigue and functional performance: a systematic review and network meta-analysis Front Nutr, 2026. PMID 42774067

Result not recorded
Design
Systematic review and network meta-analysis of 25 RCTs and 2 quasi-experimental studies
Sample
n = 1,599
Population
Adults, including clinical cohorts (NR, NMN, NADH and nicotinamide)
Funding
not stated in the PubMed or Crossref record (authors declare no commercial or financial relationships)

Search and history

Search (): (nicotinamide mononucleotide[tiab] OR nicotinamide riboside[tiab]) AND (fatigue[tiab] OR sleep[tiab] OR cognitive[tiab] OR cognition[tiab]) AND clinical trial[pt]

  • Graded C (proposed): Proposed in the monograph draft
  • C to C (approved): Editor sign-off November 13, 2026: grade matches the editor-approved final page