NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence.
Level 1 - systematic review of randomized trials
Systematic review including 28 randomized human clinical trials.
PubMed 41655607 · doi:10.1016/j.arr.2026.103057
What was done
A PRISMA-guided systematic review evaluated peer-reviewed human and rodent intervention studies published from January 2010 to October 2025 investigating oral or parenteral NAD-related compounds (including nicotinamide riboside [NR], nicotinamide mononucleotide [NMN], and direct NAD+). The review synthesized 113 eligible studies: 33 human intervention studies (28 randomized and 5 nonrandomized) and 80 rodent studies.
What was found
In 80 rodent studies, NAD+ augmentation frequently improved metabolic, mitochondrial, inflammatory, and functional outcomes, with variation across models. In humans across 33 intervention studies, oral NR and NMN consistently increased circulating and cellular NAD-related metabolites and were well tolerated over weeks to months. However, clinical effects on functional, metabolic, vascular, and other healthspan endpoints were heterogeneous and frequently null or endpoint-specific. No eligible clinical trials evaluated intravenous or intramuscular direct NAD+ for anti-aging or wellness outcomes; only one nonrandomized intravenous NMN study examining safety and biomarkers and one intravenous NAD+ pharmacokinetic pilot were identified. The abstract reports no pooled quantitative effect sizes or p-values.
Why it matters
While NAD+ precursors reliably achieve biochemical target engagement in humans, evidence supporting their efficacy for anti-aging or wellness outcomes remains inconclusive. The findings caution against assuming robust preclinical benefits automatically translate into clinical anti-aging efficacy.
Limits
Human trials were constrained by short follow-up periods (weeks to months), heterogeneous clinical endpoints, and small study cohorts. Clinical outcome trials for parenteral NAD+ formulations are completely absent. The abstract does not provide meta-analytic pooled numerical estimates.
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