Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
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DOI：
10.1507/endocrj.ej19-0313
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发表时间：
2020-01-01
影响因子：
2
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Irie, Junichiro;Inagaki, Emi;Itoh, Hiroshi
最近的研究表明，在动物模型中，细胞烟酰胺腺嘌呤二核苷酸 (NADI) 水平的下降会导致与衰老相关的疾病，而增加细胞 NAD(+) 的治疗方法可以预防这些疾病。烟酰胺单核苷酸 (NMN) 的给药已被证明可以减轻与衰老相关的功能障碍。然而，NMN 在人体中的安全性仍不清楚。 我们。因此，进行了一项临床试验，以调查 10 名健康男性单次服用 NMN 的安全性。通过单次口服 100、250 和 500 mg NMN 进行单臂非随机干预。每次干预后研究 5 小时的临床结果和参数以及 NMN 代谢物的药代动力学。干预前后还进行了眼科检查和睡眠质量评估。 单次口服NMN不会引起任何明显的临床症状或心率、血压、血氧饱和度和体温的变化。实验室分析结果没有显示显着变化，除了血清胆红素水平升高以及肌酐、氯化物和血糖水平降低在正常范围内之外，与 NMN 的剂量无关。眼科检查和睡眠质量评分结果显示前后无差异 干预后。 NMN给药后，N-甲基-2-吡啶酮-5-甲酰胺和N-甲基-4-吡啶酮-5-甲酰胺的血浆浓度显着增加，呈剂量依赖性。单次口服 NMN 在健康男性中是安全且有效代谢的，不会造成任何明显的有害影响。因此，口服 NMN 被认为是可行的，这意味着一种潜在的治疗策略 减轻人类与衰老相关的疾病。
Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NADI 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 sawn 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.