Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

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.govNCT03973203) 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. [Display omitted] •Mitochondrial myopathy patients have NAD+ deficiency in muscle and blood•Niacin is an efficient NAD+ booster in humans•Niacin improves muscle strength and fatty liver in mitochondrial myopathy•Niacin boosts muscle mitochondrial biogenesis and respiratory chain activity in humans Pirinen et al. report that niacin, a vitamin B3, can efficiently rescue NAD+ levels in the muscle and blood of patients with mitochondrial myopathy, improving disease signs and muscle strength. NAD+ levels increased also in healthy subjects. The evidence suggests that niacin is an effective NAD+ booster in humans.