Nicotinamide Riboside Restores NAD+ in RYR1-Related Muscle Diseases: Preclinical Findings

Synopsis

Mutations in the RYR1 gene cause a group of rare congenital muscle diseases (RYR1-RM) characterized by problems in calcium regulation within muscle cells, leading to muscle weakness and fatigue. This study investigated whether these disorders are linked to redox and NAD+ imbalances, which affect energy metabolism and oxidative stress. Researchers measured glutathione (GSH/GSSG) and NAD+ / NADP redox states in blood, muscle tissue, and cultured myotubes from RYR1-RM patients and mice. Most patients (68%) showed systemic NAD+ deficiency and altered NADP/NADPH ratios, indicating metabolic stress. In cell experiments, supplementation with nicotinamide riboside (NR)—a vitamin B3–derived NAD+ precursor—increased cellular NAD+ levels and enhanced mitochondrial respiration and ATP production after 72 hours. These findings suggest that NAD+ depletion contributes to muscle energy deficits in RYR1-RM and that NR supplementation could help restore mitochondrial function. Further clinical studies are needed to determine if NAD+ repletion can serve as an effective therapy for RYR1-related myopathies and other neuromuscular disorders.

Journal

Skeletal Muscle