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Supplements & CompoundsRCT · 24 weeks · age 65+Sample24-WEEK NMN TRIAL MISSES HEARING ENDPOINT

High-dose NMN raised NAD+ in older adults but did not improve hearing

A 24-week placebo-controlled trial from the University of Tokyo found that NMN reliably lifted blood NAD+ in people 65 and older, while hearing and physical performance did not measurably change.

Abstract illustration of a human inner ear cochlea beside floating molecular shapes
The trial's primary outcome was hearing, an age-related decline earlier linked to NAD+ metabolism in animal studies.Illustration
AT A GLANCE
RCT · 24 weeks · age 65+

A small randomized trial can show whether a supplement changes blood markers and selected measures over months, not whether it affects aging, disease or lifespan.

Journal
npj Aging, 25 Sep 2026
Design
Randomized, double-blind, placebo
Participants
Healthy adults aged 65+
Primary outcome
Hearing: no significant change
Funder
MIRAILAB BIOSCIENCE Inc.
STORY THREAD NAD+ precursor trials in humansFirst report in this thread. Updates will appear here.

A randomized trial in healthy older adults has found that taking a high daily amount of nicotinamide mononucleotide (NMN) for 24 weeks raised blood levels of NAD+ and related molecules, but did not improve the outcome the trial was built to test, hearing, or measures of physical performance. The results were published in npj Aging on 25 September 2026 by a team led from the University of Tokyo1.

NMN is one of the most widely sold "NAD+ booster" supplements. At 24 weeks, the new study matches the longest NMN trial durations covered by a 2026 meta-analysis5, and its result fits a pattern seen across the field: the compound reliably changes blood chemistry, while effects on how the body works are much harder to show16.

What happened

The trial was placebo-controlled, randomized, double-blind and parallel-group. Participants aged 65 and older received either 1,250 mg of NMN a day or placebo for 24 weeks1. That is five times the 250 mg a day the same group tested in an earlier 6- to 12-week trial in older men3. The amount is reported here only to describe the study; it is not a recommendation.

According to its registry entry, the trial was run at the University of Tokyo Hospital, aimed to recruit 62 men and women, and excluded people already taking supplements or health foods, smokers, people with severe hearing loss, and people with a history of cancer, heart failure or heart attack, among other conditions2. The registered primary outcome was the "change from baseline in hearing ability after 24 weeks of treatment"2.

Skeletal chemical structure diagram of nicotinamide mononucleotide
Chemical structure of nicotinamide mononucleotide (NMN), a precursor the body converts into NAD+.Image: Ed (Edgar181), public domain, via Wikimedia Commons

The evidence so far

The paper's abstract reports four main findings1:

  • NAD+ levels. Metabolomic analysis of whole blood "confirmed that oral high-dose NMN supplementation significantly increased concentrations of NAD⁺ and related metabolites."
  • Hearing and physical performance. "No significant improvement was observed in the primary endpoint of auditory function or in physical performance measures."
  • Other measures. Some body composition, lipid and dietary behavior measures showed nominal changes, but these "did not remain significant after correction for multiple testing and should be considered exploratory."
  • Safety. The supplement "was generally well tolerated, although careful safety monitoring is warranted, and did not induce significant adverse effects."

The authors' own summary: long-term high-dose NMN "robustly increases circulating NAD-related metabolites, whereas evidence for broader physiological benefit remains limited"1.

Why hearing? The same Tokyo group had earlier analyzed baseline data from its 2022 trial and reported that, in 42 healthy older men, blood levels of nicotinic acid, another molecule in the NAD+ pathway, correlated with worse hearing thresholds at some frequencies4. That paper concluded that the NAD+ pathway "might be associated" with age-related hearing loss and that further studies were warranted4. Animal studies had also linked falling NAD+ to age-related declines including hearing loss4. The new trial was a direct test of that idea in people, and on its primary measure it did not find an effect.

What it does not show yet

A negative result in one small trial does not prove NMN has no effect on hearing or function. It means this trial, at this size and length, did not detect one. Several limits apply:

  • Size. The registry lists a target of 62 participants2. A trial that small can miss modest effects.
  • Population. Participants were healthy older adults recruited at a single Tokyo hospital, without severe hearing loss and without major chronic diseases listed in the exclusion criteria2. Results may differ in other groups.
  • Duration. Twenty-four weeks is long for an NMN trial but short relative to how aging changes hearing and muscle.
  • Detail. The online version reviewed for this article presents the abstract and declarations; exact participant numbers, effect sizes and adverse event counts were not shown there.
  • Safety wording. "Generally well tolerated" comes with the authors' own note that careful safety monitoring is warranted1.

The registry also lists secondary outcomes including DNA methylation age, skin condition, six-minute walk test, gut microbiota and mitochondrial count2. The abstract does not report results for most of these, so their outcomes are not yet clear from the published summary.

Who is behind it

The corresponding authors are Masaki Igarashi and Toshimasa Yamauchi of the Department of Diabetes and Metabolic Diseases at the University of Tokyo. Co-authors come from Hiratsuka City Hospital, the University of Tokyo Hospital, Kumamoto University, the University of Toyama and MIRAILAB BIOSCIENCE Inc.1.

The study was funded by MIRAILAB BIOSCIENCE, which also supplied the NMN and gave technical support for ELISA-based biomarker measurements1. Three authors are employees of the company, and one of them also serves as its CEO, CTO and representative director1. The paper states that the company "was not involved in the study design, clinical data collection, statistical analysis, interpretation of the data, preparation of the manuscript, or the decision to submit the manuscript for publication"1. The registry lists the company as sponsor2.

How it fits the field

The result lines up with two independent reviews published earlier in 2026.

A PRISMA-guided systematic review in Ageing Research Reviews covered 33 human intervention studies of NAD-related compounds. It found that oral NR and NMN "consistently demonstrated biochemical target engagement" and were generally well tolerated, but effects on functional, metabolic, vascular and other healthspan outcomes "were heterogeneous and often null or endpoint-specific"6. It concluded that clinical effectiveness for anti-aging or wellness outcomes "remains inconclusive"6.

A meta-analysis in Nutrients, published in July 2026, pooled 15 randomized NMN trials lasting from 14 days to 24 weeks. It found no increase in adverse events or liver enzymes, and no significant effects on body weight, glucose, HbA1c, lipids or systolic blood pressure; diastolic blood pressure fell slightly5. Its authors called for larger and longer trials to confirm efficacy and long-term safety5.

StudyWhoLengthNAD+ markersFunctional outcomes
Igarashi et al., 2022Older men6 or 12 weeksIncreasedNominal gait speed and grip changes; to be validated
Igarashi et al., 2026Adults 65+24 weeksIncreasedNo significant change in hearing or physical performance

Sources:31

The 2022 trial had reported "nominally significant improvements in gait speed and performance in the left grip test, which should be validated in larger studies"3. The longer, higher-dose 2026 trial did not report significant physical performance gains1.

What to watch next

  • The full paper's numbers: how many people were randomized and completed, the size of the NAD+ rise, and adverse event counts.
  • Results for the registered secondary outcomes, including DNA methylation age and the six-minute walk test2.
  • Larger, longer trials with clinically meaningful endpoints, which both 2026 reviews say are still missing56.

For now, the clearest finding is the one the authors put first: NMN raises NAD+ in older adults' blood. Whether that change does anything people would notice remains unproven.

Questions readers ask

Did NMN improve hearing in this trial?

No significant improvement was found. Hearing was the trial's primary outcome, and the authors report no significant change compared with placebo after 24 weeks.

Did NMN raise NAD+?

Yes. Whole-blood metabolomic analysis showed significantly higher NAD+ and related metabolites in the NMN group, consistent with earlier human trials.

Was it safe?

The authors describe it as generally well tolerated with no significant adverse effects over 24 weeks, while adding that careful safety monitoring is warranted. The trial was small and not designed to detect rare or long-term harms.

Who paid for the study?

MIRAILAB BIOSCIENCE Inc. funded the trial and supplied the NMN. Three authors are company employees. The paper states the company had no role in design, data collection, analysis, interpretation or writing.

Does this mean NMN does not work for aging?

This trial cannot answer that. It found no effect on hearing or physical performance in healthy adults over 65 within 24 weeks. Reviews published in 2026 describe the human evidence for functional benefits as limited and inconclusive.

Sources

Each story is checked against the original material and independent reporting. Numbers in the text point here.

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