Endocrine Journal (Jan 2024)

Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men

  • Shintaro Yamaguchi,
  • Junichiro Irie,
  • Masanori Mitsuishi,
  • Yuichi Uchino,
  • Hideaki Nakaya,
  • Ryo Takemura,
  • Emi Inagaki,
  • Shotaro Kosugi,
  • Hideyuki Okano,
  • Masato Yasui,
  • Kazuo Tsubota,
  • Kaori Hayashi,
  • Jun Yoshino,
  • Hiroshi Itoh

DOI
https://doi.org/10.1507/endocrj.EJ23-0431
Journal volume & issue
Vol. 71, no. 2
pp. 153 – 169

Abstract

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Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD+ intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD+ levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD+ content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD+ levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD+ biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

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