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NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence

Cory Gallagher, Owoturo Oluwaseun Emmanuel
Ageing Research Reviews 2026 116:103057

Bibliography

PubMed
PMID 41655607
DOI
10.1016/j.arr.2026.103057
Competing interests
Cory Gallagher reported ownership of a management services organization serving an aesthetics clinic that did not offer NAD+ infusions or NAD+ supplementation; the authors declared no other competing interests.

Study snapshot

DesignPRISMA-guided systematic review of peer-reviewed human and rodent intervention studies published from January 2010 through October 2025, with risk-of-bias assessment.
Model33 human intervention studies (28 randomized, 5 nonrandomized) and 80 rodent intervention studies involving NAD+, NMN, NR, nicotinamide/niacin and related NAD augmentation approaches.
Sample113 eligible studies total: 33 human intervention studies and 80 rodent studies.
InterventionNAD-related compounds including oral NMN, NR, nicotinamide/niacin and contextual parenteral NAD-related approaches.
DurationIncluded human studies ranged from acute assessments to several months; review search window January 2010–October 2025.
EndpointsNAD-related biomarkers; Physical performance; Fatigue and energy; Sleep and circadian outcomes; Vascular function; Blood pressure; Body composition; Insulin sensitivity; Lipids; Inflammation; Quality of life; Skin-aging outcomes; Safety and tolerability

What the study showed, in plain terms

This 2026 systematic review mapped the wider NAD-augmentation literature across 33 human intervention studies and 80 rodent studies.

Its central conclusion is highly relevant to NMN: oral NMN and NR consistently demonstrate biochemical target engagement in humans and are generally well tolerated over weeks to months, but clinical effects on metabolism, vascular function, physical performance and other healthspan outcomes are heterogeneous and often null or limited to specific endpoints.

The review also found no eligible controlled outcomes trials of intravenous or intramuscular NAD+ itself for anti-aging or wellness. That makes it a useful umbrella source for separating proven NAD biomarker changes from much weaker claims about general rejuvenation.

Key findings

  • The review included 113 studies: 33 human intervention studies and 80 rodent studies.
  • Twenty-eight of the 33 human studies were randomized trials.
  • Oral NMN and NR consistently increased circulating or cellular NAD-related biomarkers.
  • Clinical and functional benefits in humans were heterogeneous, often null, or specific to particular endpoints and populations.
  • No eligible outcomes trials evaluated IV or IM NAD+ itself for anti-aging or wellness indications.
  • Risk-of-bias concerns were common: only one randomized human trial received an overall low-risk judgment, with 23 rated some concerns and four high risk.

What this study can and cannot tell us

The review pooled several NAD-related compounds and routes conceptually rather than performing a single quantitative NMN-only meta-analysis, so compound-specific conclusions still require the underlying NMN trials and dedicated meta-analyses.

Human trials were heterogeneous in population, dose, formulation, duration and outcome definitions.

The literature search ended in October 2025, so several 2026 NMN publications are outside its primary search window even though the review itself was published in 2026.

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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