Tier 3 — preclinical

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

Junichiro Irie, Emi Inagaki, Masataka Fujita, Hideaki Nakaya, Masanori Mitsuishi, Shintaro Yamaguchi, Kazuya Yamashita, Shuhei Shigaki, Takashi Ono, Hideo Yukioka, Hideyuki Okano, Yo-ichi Nabeshima, Shin-ichiro Imai, Masato Yasui, Kazuo Tsubota, Hiroshi Itoh
Endocrine Journal 2020 67(2), 153-160

Bibliography

PubMed
PMID 31685720
DOI
10.1507/endocrj.EJ19-0313
Funding
The disclosure states that Hiroshi Itoh received research funding from Oriental Yeast Co., Ltd.; NMN capsules used in the study were provided by Oriental Yeast Co., Ltd.
Competing interests
Shin-ichiro Imai is an inventor on NMN-use and SLC12A8 NMN-transporter patents licensed to MetroBiotech and Teijin. Shuhei Shigaki, Takashi Ono and Hideo Yukioka were employees of Shionogi & Co., Ltd. Hiroshi Itoh received research funding from Oriental Yeast Co., Ltd.

Study snapshot

DesignSingle-arm, nonblinded, nonrandomized dose-escalation clinical study; each participant received single oral doses of 100, 250 and 500 mg NMN on separate visits more than one week apart.
ModelTen healthy Japanese men aged 40-60 years, excluding participants with major medical, metabolic, psychiatric, ophthalmic or allergic disorders.
Samplen=10 healthy men.
InterventionSingle oral NMN doses of 100 mg, 250 mg and 500 mg at 09:00 after an overnight fast, with five hours of monitoring after each dose and more than one week between visits.
DurationAcute: 5-hour monitoring after each single dose; three dose visits separated by more than one week.
EndpointsClinical symptoms and adverse events; Heart rate, blood pressure, oxygen saturation and body temperature; Routine blood and urine laboratory measures; Plasma nicotinamide metabolites MNA, 2Py and 4Py; Ophthalmic examinations; Pittsburgh Sleep Quality Index

What the study showed, in plain terms

This early human study asked a basic question: can single oral doses of NMN up to 500 mg be given to healthy adults without obvious short-term safety problems, and what happens to downstream nicotinamide metabolites?

Ten healthy men received 100, 250 and 500 mg on separate visits. No severe adverse events or clinically important changes in vital signs, ophthalmic measures or most laboratory tests were observed. Changes in bilirubin, glucose, creatinine and chloride remained within reference ranges and were not dose dependent.

The clearest pharmacokinetic signal was a dose-related rise in the downstream metabolites 2Py and 4Py. The study did not directly quantify plasma NMN or tissue NAD+, so it supports acute tolerability and metabolism rather than proof that the doses raised tissue NAD+ or produced clinical benefit.

Key findings

  • Single oral doses of 100, 250 and 500 mg NMN were reported as well tolerated in 10 healthy men, without severe adverse events such as flushing or gastrointestinal symptoms.
  • Heart rate, blood pressure, oxygen saturation and body temperature were not materially altered after dosing.
  • Serum bilirubin increased and glucose, creatinine and chloride decreased, but the changes remained within normal ranges and were not dose dependent; the authors considered fasting a likely contributor.
  • Plasma 2Py and 4Py increased significantly after NMN and showed dose-dependent exposure, supporting systemic metabolism of the administered NMN.
  • PSQI sleep scores and ophthalmic assessments did not show meaningful pre/post differences.

What this study can and cannot tell us

The study had no placebo control, so changes in laboratory measures cannot be cleanly separated from the effects of five hours of fasting.

The sample included only 10 healthy men and assessed single doses, providing little information about women, older populations, chronic dosing or clinical efficacy.

The investigators could not detect plasma NMN, likely because of sample handling and rapid NMN degradation, and they did not measure tissue NAD+.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology