Research paper

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study

Mijin Kim, Jaehoon Seol, Toshiya Sato, Yuichiro Fukamizu, Takanobu Sakurai, Tomohiro Okura

Nutrients 2022 Volume 14, Issue 4, article 755

Tier 2 · Single well-powered human RCT or comprehensive human reviewSleep and Performance

Source identifiers

DOI 10.3390/nu14040755
PubMed PMID 35215405
Funding This study was supported by the Mitsubishi Corporation Life Sciences Ltd. The Mitsubishi Corporation Life Sciences Ltd., provided the research funds, experimental supplements and APC. The funders had no role in data collection, interpretation of the data, the writing, or submission of this publication.
Declared competing interests The authors declare no conflict of interest.

Study snapshot

Design
Randomised, double-blind, placebo-controlled, parallel-group, 2×2 factorial trial (dose timing × treatment)
Population
Community-dwelling Japanese adults aged 65 years and older, without dementia, not requiring long-term care, with independent mobility. Recruited in Tsukuba City.
Sample
n = 108, randomly allocated to four groups of 27 (NMN morning, NMN evening, placebo morning, placebo evening), stratified by sex, age band, and reported poor sleep
Intervention
250 mg NMN or matching placebo (six tablets) taken once daily for 12 weeks. Morning groups took the dose between waking and noon; evening groups took it between 18:00 and bedtime. Intake was recorded in participant diaries.
Endpoints
Sleep quality (Pittsburgh Sleep Quality Index — primary); Subjective fatigue (Jikaku-sho shirabe questionnaire, five subscales — primary); Grip strength; 5-times sit-to-stand; Timed up-and-go; 5-metre habitual walk

What the study found, in plain language

This trial tested a question the earlier NMN trials had not asked: does the time of day at which NMN is taken change its effects? One hundred and eight Japanese adults aged 65 and over were randomised into four groups — NMN in the morning, NMN in the evening, placebo in the morning, or placebo in the evening — and took 250 mg once daily for twelve weeks. The primary outcomes were sleep quality and subjective fatigue; physical performance was a secondary outcome.

Two significant group-by-time interactions emerged. Lower-limb function measured by the 5-times sit-to-stand test improved in all four groups after twelve weeks, but the effect was largest in the evening-NMN group (Cohen's d = 0.72). Self-reported drowsiness — one of five subscales on the fatigue questionnaire — improved significantly in both evening groups (NMN and placebo) but not in the morning groups; again the largest effect size was in the evening-NMN group (d = 0.64).

Total sleep quality on the PSQI did not show a significant group-by-time interaction, though the evening-NMN group had the largest effect sizes across several subscales including sleep quality score (d = 0.80) and daytime dysfunction (d = 0.72). Grip strength and 5-metre walk speed did not change. The authors interpret the pattern as suggestive that evening dosing may be more effective for lower-limb function and reduced drowsiness in older adults, while acknowledging the placebo group also improved on several measures.

Key findings

  • Significant group × time interaction for 5-times sit-to-stand (p = 0.04); all four groups improved post-intervention, with the largest effect in the evening-NMN group (d = 0.72).
  • Significant group × time interaction for drowsiness (p = 0.02); both evening groups (NMN and placebo) improved at mid- and post-intervention, with the largest effect in the evening-NMN group (d = 0.64).
  • Timed up-and-go improved with a medium effect in the evening-NMN group (d = 0.54) but the interaction was not significant.
  • Total PSQI global score showed no significant interaction; effect sizes were largest in the evening-NMN group (d = 0.68) across sleep quality, sleep latency, and daytime dysfunction subscales.
  • Grip strength and 5-metre habitual walk speed did not change in any group.
  • Metabolic markers, fasting glucose, and lipids were not reported as primary outcomes.
  • Intake adherence exceeded 95% in all groups.

What this study can and cannot tell us

  • Placebo groups also improved on several outcomes, including 5-times sit-to-stand and evening drowsiness. The authors note participants may have perceived the placebo as NMN, given the disclosure required by research ethics. This weakens the specificity of the NMN attribution.
  • Sleep, fatigue, and drowsiness were assessed by subjective questionnaires only. Objective measures (actigraphy, polysomnography, sleep diary) were not used.
  • No physiological or biochemical measurements were taken; the study could not confirm that NMN raised NAD+ in these participants, nor link measured effects to a mechanism.
  • Dietary NMN intake and overall nutrient intake were not tracked, so background exposure to NMN from food is unaccounted for.
  • Total PSQI score, the pre-specified primary sleep outcome, did not show a significant group-by-time interaction. Positive findings on drowsiness and 5-STS should be read as a specific pattern within a broader set of null results.
  • Population was Japanese adults aged 65+ living in Tsukuba City; generalisability to other populations is not established.
  • Tier-2 evidence: single RCT with mixed positive-and-null findings; independent replication is needed before firm efficacy conclusions.