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Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

Keisuke Okabe, Keisuke Yaku, Yoshiaki Uchida, Yuichiro Fukamizu, Toshiya Sato, Takanobu Sakurai, Kazuyuki Tobe, Takashi Nakagawa
Frontiers in Nutrition 2022 9:868640

Bibliography

PubMed
PMID 35479740
PubMed Central
PMC9036060
DOI
10.3389/fnut.2022.868640
Funding
Funded by Mitsubishi Corporation Life Sciences Limited. JSPS KAKENHI Grant 20K2065, the Tamura Science and Technology Foundation, and Moonshot R&D Grant JPMJMS2021 supported maintenance of the metabolomics facilities.
Competing interests
Yoshiaki Uchida, Yuichiro Fukamizu, Toshiya Sato and Takanobu Sakurai were employees of Mitsubishi Corporation Life Sciences Limited and prepared the NMN and placebo; the remaining authors reported no commercial or financial relationships that could be construed as a conflict.

Study snapshot

DesignRandomized, double-blind, placebo-controlled parallel-group trial.
ModelHealthy adults aged 20–65 years.
Sample30 randomized: 15 NMN and 15 placebo. One placebo participant withdrew after the 8-week visit, leaving 29 participants to complete the 12-week study.
InterventionNMN 250 mg/day versus placebo.
Duration12 weeks.
EndpointsSafety laboratory and physiological measures; Whole-blood NAD+; Whole-blood NMN and related metabolites including NAMN

What the study showed, in plain terms

Thirty healthy adults were randomized to 250 mg/day of NMN or placebo for 12 weeks. The main questions were whether repeated dosing was well tolerated and whether it raised whole-blood NAD+.

NMN significantly increased whole-blood NAD+ and NAMN without an obvious safety signal. The trial did not demonstrate that raising NAD+ translated into a clinical health benefit.

Key findings

  • Whole-blood NAD+ increased significantly with NMN and remained elevated through the supplementation period.
  • NAMN increased, whereas circulating NMN itself did not show a comparable increase.
  • No obvious adverse effects or clinically concerning laboratory abnormalities were reported over 12 weeks.

What this study can and cannot tell us

The trial was small and conducted in healthy adults, so it was not designed to establish clinical efficacy or long-term safety. One placebo participant withdrew after the 8-week visit. The main pharmacodynamic endpoint was whole-blood NAD+ rather than target-tissue NAD+. Mitsubishi Corporation Life Sciences Limited funded the study and manufactured the NMN and placebo, and four authors were company employees.

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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