Effects of Nicotinamide Riboside on Mitochondrial Function in Rare Mitochondrial Disorder: Preclinical Findings

Synopsis

Nicotinamide riboside (NR), a vitamin B3 derivative and precursor to NAD+, is known to support mitochondrial function and energy metabolism in many conditions. Researchers tested whether NR could help mice with mitochondrial complex III deficiency—a genetic disorder that causes severe liver disease (hepatopathy) and NAD+ depletion. Although NR supplementation successfully increased NAD+ biosynthesis activity, it did not raise total liver NAD+ levels or improve mitochondrial respiration, liver function, or survival in the affected mice. The study revealed that these mice were in a starvation-like metabolic state, which already triggered SIRT1 and SIRT3 activation through AMPK and cAMP signaling, independent of NAD+. This may explain why additional NR had no therapeutic effect. Overall, the findings show that simply boosting NAD+ precursors may not benefit all forms of mitochondrial dysfunction. A deeper understanding of each disease’s metabolic state is essential before applying NAD-based therapies.

Journal

The FASEB Journal