Tier 2 — strong

Sustained NAD⁺ augmentation by high-dose nicotinamide mononucleotide supplementation in older adults: a 24-week randomized, double-blind, placebo-controlled trial

Igarashi M, Naruse K, Takaoka Y, Miura M, Kashiwabara K, Sawada M, Sekine R, Kubota N, Suzuki M, Yoshida Y, Shimizu N, Yaku K, Nakagawa T, Yamauchi T
npj Aging 2026 Early online publication; final volume/issue/pages not yet assigned at verification

Bibliography

DOI
10.1038/s41514-026-00482-7
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Funded by MIRAILAB BIOSCIENCE Inc., which also provided the NMN used in the study.
Competing interests
M.S., Y.Y. and N.Sh. were employees of MIRAILAB BIOSCIENCE Inc.; N.Sh. also served as CEO, CTO and Representative Director. The company supplied NMN and technical support for ELISA-based biomarker measurements. The paper states that the company was not involved in study design, clinical data collection, statistical analysis, interpretation, manuscript preparation or the submission decision. Other authors declared no competing interests.

Study snapshot

DesignRandomized, double-blind, placebo-controlled, parallel-group human trial registered as jRCTs031220373.
ModelHealthy older adults aged ≥65 years; both men and women; restrictive eligibility excluded many chronic conditions and regular medication use.
SampleRegistered target: 62 participants; 2026 conference abstract reported 31 NMN and 31 placebo. The article abstract does not state the final analyzed sample.
InterventionNMN 1,250 mg/day orally (5 × 250 mg tablets once daily) versus matching placebo.
Duration24 weeks
EndpointsChange from baseline in auditory function after 24 weeks (primary); Whole-blood NAD+ and related metabolites; Physical function and exercise tolerance; Blood tests and aging-related biomarkers; DNA methylation age; Skin condition; Gut and oral microbiota; Mitochondrial measures; Quality of life and dietary behavior; Safety and adverse events

What the study showed, in plain terms

This 2026 randomized, double-blind, placebo-controlled trial tested whether a comparatively high oral NMN dose could sustain NAD+ augmentation and improve age-related physiological outcomes in adults aged 65 years or older.

Participants were assigned to 1,250 mg/day NMN or placebo for 24 weeks. The registered target sample size was 62, and a 2026 conference abstract described 31 participants per group. The primary endpoint was change in auditory function; the protocol also evaluated physical function, blood biomarkers, body composition, skin, exercise tolerance, microbiota, mitochondrial measures and quality of life.

NMN robustly increased whole-blood NAD+ and related metabolites, confirming durable target engagement at 24 weeks. However, the trial did not significantly improve the primary auditory endpoint or physical-performance measures.

Nominal changes were reported in some body-composition, lipid-related and dietary-behavior measures, but they did not remain significant after correction for multiple testing. The practical interpretation is that sustained high-dose NMN clearly changes NAD biology, while evidence for broader physiological benefit remains limited.

Key findings

  • Oral NMN at 1,250 mg/day for 24 weeks significantly increased whole-blood NAD+ and related metabolites in adults aged 65 years or older.
  • The primary endpoint, auditory function, did not significantly improve compared with placebo.
  • Physical-performance measures did not show a significant benefit.
  • Some body-composition, lipid-related and dietary-behavior measures changed nominally, but these findings did not survive correction for multiple testing and should be considered exploratory.
  • High-dose NMN was generally well tolerated over 24 weeks and no significant adverse effects were reported, although the authors explicitly advised careful safety monitoring.

What this study can and cannot tell us

The study population consisted of comparatively healthy older adults aged at least 65 years who were selected using restrictive eligibility criteria, so the results should not automatically be generalized to younger adults or people with substantial chronic disease, polypharmacy or frailty.

The primary endpoint was auditory function. Many aging-related outcomes were secondary or exploratory, and nominal signals in body composition, lipids and dietary behavior did not remain significant after correction for multiple testing.

Twenty-four weeks is longer than many NMN trials but is still insufficient to establish effects on chronic disease incidence, disability, biological aging trajectories or lifespan.

The trial was funded by MIRAILAB BIOSCIENCE Inc., which also supplied the NMN. Three authors were company employees, including one who served as CEO, CTO and Representative Director. The paper states that the company was not involved in study design, clinical data collection, statistical analysis, data interpretation, manuscript preparation or the decision to submit.

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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