Nicotinamide Riboside Partially Restores Cellular Energy in Mitochondrial Disease: Preclinical Findings

Synopsis

Mitochondrial diseases arise from genetic mutations that impair energy production in cells. One of the most common, the m.3243A>G mutation, disrupts complex I of the mitochondrial respiratory chain, lowering energy output and disturbing the NAD+/NADH balance essential for metabolism. In this study, scientists treated fibroblasts from patients carrying this mutation with nicotinamide riboside (NR)—a vitamin B3–derived NAD+ booster—and a mitochondrial enzyme therapy (mitoLbNOX) that reduces excess NADH. Cells with the mutation showed low complex I activity, poor oxygen consumption, and reduced ATP levels, but NR treatment partially restored NAD+/NADH balance and energy production. MitoLbNOX treatment was even more effective, significantly increasing ATP and oxygen use while lowering NADH buildup. The results suggest that combining NAD+ supplementation with therapies that remove NADH overload could better restore mitochondrial energy balance in patients with m.3243A>G-related mitochondrial disorders.

Journal

Frontiers in Physiology