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

Summary

The first published single-dose pharmacokinetic and safety study of oral NMN in humans. Ten healthy Japanese men (ages 40-60) received a single oral dose of NMN at 100, 250, or 500 mg, with serial blood sampling over five hours and clinical chemistry monitoring. NMN was well tolerated at all three doses, with no serious adverse events and no clinically significant changes in vital signs, sleep quality, or laboratory panels (liver enzymes, kidney function, glucose, lipids). Plasma concentrations of NMN itself remained largely undetectable by LC-MS, but downstream NAD+ metabolites — particularly N-methyl-nicotinamide (MeNAM) and N-methyl-2-pyridone-5-carboxamide (2PY) — rose dose-dependently within 30 minutes, consistent with rapid conversion of NMN to NAD+ and subsequent metabolic processing. Bilirubin rose slightly and uric acid fell slightly at higher doses, both within clinical reference ranges. The study established acute safety at single doses up to 500 mg and is the foundational human PK data underpinning all subsequent NMN trial dose selection. Limitations include small cohort, single-dose design, and indirect readout of NAD+ via downstream metabolites rather than direct tissue measurement.

For background on the compound studied here, see our NMN precursor reference.

Frequently asked questions

What did Irie et al. (2020) find about NMN?

Single oral NMN doses up to 500 mg are safe and well-tolerated in healthy men, with dose-dependent rises in downstream NAD+ metabolites. Source: Irie J, Inagaki E, Fujita M, et al. "Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men." Endocrine Journal, 2020.

What kind of study is Irie 2020?

It is a pk study on NMN published in Endocrine Journal in 2020. The first published single-dose pharmacokinetic and safety study of oral NMN in humans. Ten healthy Japanese men (ages 40-60) received a single oral dose of NMN at 100, 250, or 500 mg, with serial blood sampling over five hours and clinical chemistry monitoring. NMN was well tolerated at all three doses, with no serious adverse events and no clinically significant changes in vital signs, sleep quality, or laboratory panels (liver enzymes, kidney function, glucose, lipids). Plasma concentrations of NMN itself remained largely undetectable by LC-MS, but downstream NAD+ metabolites — particularly N-methyl-nicotinamide (MeNAM) and N-methyl-2-pyridone-5-carboxamide (2PY) — rose dose-dependently within 30 minutes, consistent with rapid conversion of NMN to NAD+ and subsequent metabolic processing. Bilirubin rose slightly and uric acid fell slightly at higher doses, both within clinical reference ranges. The study established acute safety at single doses up to 500 mg and is the foundational human PK data underpinning all subsequent NMN trial dose selection. Limitations include small cohort, single-dose design, and indirect readout of NAD+ via downstream metabolites rather than direct tissue measurement.

Where can I read the full Irie 2020 paper?

The primary source is available on PubMed (PMID 31685720) and via DOI 10.1507/endocrj.EJ19-0313.

Access the full paper

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