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

Yixuan Gao, Shengnian Li, Jingjun Guan, Yikun Yin, Xianghao Kong, Liang Yu
Frontiers in Nutrition 2026 13:1890335

Bibliography

DOI
10.3389/fnut.2026.1890335
Competing interests
The authors declared that the work was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest.

Study snapshot

DesignSystematic review and network meta-analysis registered in PROSPERO (CRD420251237193), with RoB 2 and GRADE assessment.
ModelAdults across healthy and clinical populations receiving NMN, NR, NADH or NAM; 27 included studies, including 7 NMN studies.
Sample27 studies; 1,599 total participants. Seven NMN studies included 370 participants.
InterventionNAD+ precursor supplementation (NMN, NR, NADH or NAM) versus placebo/control, with domain-specific analyses of perceived fatigue, endurance, strength, cognition, quality of life and sleep.
DurationIncluded studies ranged from approximately 2 to 48 weeks, with most lasting 4–12 weeks.
EndpointsPerceived fatigue; Aerobic capacity/endurance; Neuromuscular strength; Cognitive performance; Quality of life; Sleep quality

What the study showed, in plain terms

This September 2026 synthesis separates subjective fatigue from objective performance rather than treating 'energy' as one outcome. Across 27 studies of several NAD+ precursors, no precursor significantly improved perceived fatigue or sleep quality.

For NMN specifically, the network model found statistically significant endurance-related effects at medium and high dose, while neuromuscular strength remained unchanged and NMN did not show a cognitive-performance benefit.

The result should be interpreted alongside the network structure: most comparisons were against placebo rather than direct active head-to-head trials, populations and endpoints were heterogeneous, and the authors explicitly call the comparative rankings indirect and in need of longer domain-specific RCTs.

Key findings

  • No NAD+ precursor significantly improved perceived fatigue in the network analysis.
  • Medium-dose NMN improved endurance-related outcomes in the network model (SMD 0.66, 95% CI 0.09–1.23).
  • High-dose NMN improved endurance-related outcomes in the network model (SMD 1.02, 95% CI 0.43–1.60).
  • Neuromuscular strength outcomes remained unchanged; the matching aggregate meta-analysis did not show a significant overall strength benefit.
  • NMN did not show the cognitive-performance effect observed for NADH.
  • No meaningful improvement in sleep quality was established.
  • Quality-of-life signals were modest and dose-dependent for some NMN categories.

What this study can and cannot tell us

This is not an NMN-only synthesis: the network includes NR, NADH and NAM as well as NMN, and only seven included studies evaluated NMN.

Most treatment networks were placebo-centered with few direct head-to-head comparisons between active precursors, so SUCRA rankings and indirect comparisons require caution.

Dose categories, populations and outcome definitions were heterogeneous. Positive endurance estimates should not be converted into a universal athletic-performance claim.

The search covered studies through January 1, 2026, so later 2026 trials such as the collegiate-athlete NMN trial are not fully represented in the synthesis.

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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