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

• Published in: ENDOCRINE JOURNAL Vol. 71; no. 2; pp. 153 - 169
• Main Authors: Yamaguchi, Shintaro, Irie, Junichiro, Mitsuishi, Masanori, Uchino, Yuichi, Nakaya, Hideaki, Takemura, Ryo, Inagaki, Emi, Kosugi, Shotaro, Okano, Hideyuki, Yasui, Masato, Tsubota, Kazuo, Hayashi, Kaori, Yoshino, Jun, Itoh, Hiroshi
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01.01.2024; Japan Science and Technology Agency
• Subjects: Aging; Animal models; Biosynthesis; Cardiovascular disease; Coronary artery disease; Heart diseases; Hyperinsulinemia; Leukocytes (mononuclear); Metabolism; Middle age; NAD; Nicotinamide adenine dinucleotide; Nicotinamide mononucleotide; Obesity; Oral administration; Peripheral blood mononuclear cells; Postprandial hyperinsulinemia; Risk factors; Sleep; Nicotinamide adenine dinucleotide; Postprandial hyperinsulinemia; Metabolism; Nicotinamide mononucleotide
• ISSN: 0918-8959; 1348-4540; 1348-4540
• DOI: 10.1507/endocrj.EJ23-0431

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.