Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Open accessAbstract
prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.
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Increases in these metabolites after oral NMN suggest increased muscle NAD+ turnover by NMN.
“Irie et al. [40] also observed the raising of these metabolites after oral NMN supplementation, suggesting increased muscle NAD+ turnover by NMN [40].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [40]
The Results report increased plasma 2Py and 4Py after oral NMN, and the Discussion speculates that NMN increased tissue NAD+ and plasma metabolites. The paper does not establish increased muscle NAD+ turnover: the Discussion says tissue NAD+ was not measured and proposes skeletal-muscle biopsies for future study. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNMN was not detected in plasma in that trial, most likely because sample freezing before extraction caused NMN degradation.
“However, NMN was not detected in plasma, most likely because the sample freezing before extraction may have caused NMN degradation [40].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [40]
A single oral dose of NMN from 100 to 500 mg was safely and effectively metabolized in healthy subjects, with significant dose-dependent increases in plasma metabolites and no adverse effects or significant clinical changes.
“The first clinical trial reported that a single oral dose of NMN (from 100 to 500 mg) was safely and effectively metabolized in healthy subjects. It showed a significant increase of metabolites in plasma in a dose-dependent manner, without causing adverse effects or any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature [40].”
From NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health (2023) · cites this paper as [40]
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- Authors
- Irie, J., Inagaki, E., Fujita, M., Nakaya, H., Mitsuishi, M., Yamaguchi, S., Yamashita, K., Shigaki, S., Ono, T., Yukioka, H., Okano, H., Nabeshima, Y.-I., Imai, S.-I., Yasui, M., Tsubota, K., & Itoh, H.
- Affiliations
- Keio University (JP)
- Shionogi (Japan) (JP)
- Foundation for Biomedical Research and Innovation (JP)
- Washington University in St. Louis (US)
- ORCID
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 2020
- Volume
- 67
- Issue
- 2
- Pages
- 153-160
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- OpenAlex
- W2984194295
- Cited by
- 191
- References
- 21
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 25 · 2023: 28 · 2022: 32 · 2021: 39 · 2020: 15
- FWCI
- 11.30
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Keio University
- Shionogi
- Japan Society for the Promotion of Science (17H06270, 18K08526, 17H04353, 18K15399, 20H00535)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- nicotinamide mononucleotide, oral administration, safety, pharmacokinetics, dose dependence, serum bilirubin, sleep quality, age-related diseases, healthy men
- MeSH terms
- Administration, Oral, Adult, Bilirubin, Blood Glucose, Blood Pressure, Body Temperature, Chlorides, Chromatography, Liquid, Creatinine, Diagnostic Techniques, Ophthalmological, Dose-Response Relationship, Drug, Electrocardiography, Heart Rate, Humans, Intraocular Pressure, Japan, Male, Middle Aged, Niacinamide, Nicotinamide Mononucleotide, Oxygen, Pyridones, Sleep, Visual Acuity, Tandem Mass Spectrometry, Healthy Volunteers
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