Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men

This single-arm open-label study screened 28 healthy Japanese men aged 40–60 years. Fourteen were eligible, 13 began a four-week placebo period, and nine completed all planned examinations after a two-week washout and eight weeks of NMN at 250 mg/day.

Among the nine completers, trough PBMC NAD+ concentrations increased over the NMN period. The investigators also examined glucose and insulin responses, ophthalmologic measures, sleep, and other safety outcomes. A possible reduction in postprandial hyperinsulinemia was reported in a subgroup of three participants with insulin oversecretion at baseline.

The study has no parallel placebo-control group for the NMN phase and experienced five post-screening dropouts. It therefore contributes exploratory safety and NAD pharmacodynamic evidence rather than confirmatory evidence of clinical benefit.

• PBMC NAD+ increased over the eight-week supplementation period.
• The 250 mg/day regimen was reported as well tolerated.
• A possible attenuation of postprandial hyperinsulinemia was observed in a subgroup of three participants with baseline insulin oversecretion.
• The study collected broad metabolic, ophthalmologic and sleep measures but did not provide placebo-controlled efficacy estimates.
• The study's open-label single-arm design limits causal inference.

• Small and incomplete cohort: 14 participants were eligible, 13 started the placebo period, and only 9 completed all planned examinations and the 8-week NMN period.
• There was no parallel placebo or untreated control group during the NMN phase; the study used a preceding placebo period instead.
• The postprandial-hyperinsulinemia signal involved only three participants and is highly exploratory.
• The intervention tested one dose, 250 mg/day, for eight weeks; long-term clinical safety and efficacy were not established.
• Three participants developed mild transaminase elevations at different stages (placebo, washout, or NMN periods), and one participant developed elevated intraocular pressure during the NMN period; causality was not established.
• The publication discloses NAD/NMN-related patents and research funding from Oriental Yeast Company, which also supplied the placebo and NMN capsules.