Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men

This was the first published human study of nicotinamide mononucleotide (NMN). Ten healthy Japanese men in their 40s and 50s received single oral doses of 100 mg, 250 mg, and 500 mg NMN on separate visits, and were monitored for five hours after each dose. The purpose was not to test whether NMN works, but whether it is safe to take at these doses and whether the body absorbs and metabolises it.

The doses were well tolerated. None of the participants experienced flushing, nausea, or the gastrointestinal effects sometimes reported with high-dose nicotinamide. Vital signs, ophthalmic examinations, and sleep quality scores were unchanged before and after each dose. Small changes in serum bilirubin, glucose, chloride, and creatinine were observed, but the authors attributed these to the five-hour fast rather than to NMN, and all values stayed within normal ranges.

Plasma concentrations of two downstream NMN metabolites — 2Py and 4Py — rose significantly and in a dose-dependent way, showing that orally administered NMN was absorbed and processed. NMN itself was not measurable in plasma, which the authors attributed to sample-handling degradation rather than absence of uptake.

• No significant changes in heart rate, blood pressure, oxygen saturation, or body temperature at any of the three doses.
• No adverse events reported, including no flush and no gastrointestinal symptoms.
• Serum bilirubin rose 51.3% and glucose fell 11.7% at 300 minutes across all doses; both changes stayed within normal ranges and the authors attributed them to the 5-hour fast, not NMN.
• Plasma 2Py and 4Py rose significantly and dose-dependently; the incremental area under the curve was significantly greater at 500 mg than at 100 mg or 250 mg.
• 2Py and 4Py incremental areas were strongly correlated (r = 0.989), and the 2Py:4Py ratio was constant across subjects, indicating consistent metabolism of NMN to its downstream products.
• Sleep quality (PSQI) and ophthalmic parameters were unchanged after each dose.

• Not placebo-controlled: the study cannot separate NMN effects from effects of the 5-hour fast itself. The authors flag this explicitly for the bilirubin and glucose findings.
• Single-dose design only. Long-term safety and efficacy were not evaluated.
• Small sample (n = 10) and single-sex (men only) limit generalisability.
• Plasma NMN itself was not detected, most likely because of degradation during sample handling. Direct pharmacokinetics of the parent compound could not be characterised.
• Tissue NAD+ levels were not measured; increases in downstream metabolites are indirect evidence of NMN uptake, not direct evidence of raised tissue NAD+.
• Tier-4 evidence: hypothesis-generating for safety at these doses. Does not establish clinical efficacy.