NAD⁺ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD⁺ depletion occurs in patients with degenerative disorders and whether NAD⁺ repletion improves their symptoms has remained open. Here, we report systemic NAD⁺ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD⁺-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD⁺ increased in all subjects, up to 8-fold, and muscle NAD⁺ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD⁺ deficiency and points niacin to be an efficient NAD⁺ booster for treating mitochondrial myopathy.

NAD ⁺是一种氧化还原活性代谢物，已提出消耗其会促进啮齿动物的衰老和退行性疾病。然而，NAD ⁺消耗是否会发生在退行性疾病患者中，以及 NAD ⁺补充是否能改善他们的症状仍然没有定论。在这里，我们报告了成人发病的线粒体肌病患者的全身性 NAD ⁺缺乏症。我们为患者及其匹配的对照组分别施用了增加剂量的 NAD ^{+ -}助推剂烟酸，一种维生素 B3 形式（至 750–1,000 毫克/天；clinicaltrials.gov NCT03973203），分别持续 10 或 4 个月。所有受试者的血液 NAD ⁺增加，高达 8 倍，肌肉 NAD ⁺患者达到了他们的控制水平。部分患者表现出贫血倾向，而所有受试者的肌肉力量和线粒体生物合成均增加。在患者中，肌肉代谢组转向对照组，肝脏脂肪甚至减少了 50%。我们的证据表明，血液分析有助于识别 NAD ⁺缺乏症，并指出烟酸是治疗线粒体肌病的有效 NAD ⁺助推器。