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

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.

• 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.

• 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.