著者
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
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ19-0313, (Released:2019-11-02)
被引用文献数
8 115

Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ 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.
著者
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
出版者
The Japan Endocrine Society
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.67, no.2, pp.153-160, 2020 (Released:2020-02-28)
参考文献数
21
被引用文献数
22 115

Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ 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.
著者
Hinako Oshiro Junichi Hata Daisuke Nakashima Naoya Hayashi Yawara Haga Kei Hagiya Daisuke Yoshimaru Hideyuki Okano
出版者
Japanese Society for Magnetic Resonance in Medicine
雑誌
Magnetic Resonance in Medical Sciences (ISSN:13473182)
巻号頁・発行日
pp.mp.2022-0103, (Released:2023-02-08)
参考文献数
37

Purpose: Diffusion MRI is a physical measurement method that quantitatively indicates the displacement of water molecules diffusing in voxels. However, there are insufficient data to characterize the diffusion process physically in a uniform structure such as a phantom. This study investigated the transitional relationship between structure scale, temperature, and diffusion time for simple restricted diffusion using a capillary phantom.Methods: We performed diffusion-weighted pulsed-gradient stimulated-echo acquisition mode (STEAM) MRI with a 9.4 Tesla MRI system (Bruker BioSpin, Ettlingen, Germany) and a quadrature coil with an inner diameter of 86 mm (Bruker BioSpin). We measured the diffusion coefficients (radial diffusivity [RD]) of capillary plates (pore sizes 6, 12, 25, 50, and 100 μm) with uniformly restricted structures at various temperatures (10ºC, 20ºC, 30ºC, and 40ºC) and multiple diffusion times (12–800 ms). We evaluated the characteristics of scale, temperature, and diffusion time for restricted diffusion.Results: The RD decayed and became constant depending on the structural scale. Diffusion coefficient fluctuations with temperature occurred mostly under conditions of a large structural scale and short diffusion time. We obtained data suggesting that temperature-dependent changes in the diffusion coefficients follow physical laws.Conclusion: No water molecules were observed outside the glass tubes in the capillary plates, and the capillary plates only reflected a restricted diffusion process within the structure.We experimentally evaluated the characteristics of simple restricted diffusion to reveal the transitional relationship of the diffusion coefficient with diffusion time, structure scale, and temperature through composite measurement.