Evaluation of Nicotinamide Riboside in Prevention of Small Nerve Fiber Axon Degeneration and Promotion of Nerve Regeneration

ABSTRACT Background and Aims Recent preclinical studies have shown that nicotinamide adenine dinucleotide (NAD + ) plays a critical role in molecular mechanisms of axon degeneration, and reductions in NAD + levels are associated with axonal degeneration. Nicotinamide riboside (NR) is a safe and widely available pyridine‐nucleoside form of vitamin B3 and is an NAD + precursor. Methods To investigate if oral supplementation of synthetic NR can act as a therapeutic agent to prevent degeneration of small somatic sensory axons innervating the skin or promote regeneration of these same fibers in humans, we utilized a validated experimental model of cutaneous nerve degeneration and regeneration and conducted a placebo‐controlled, double‐blinded Phase 2 study. Results NR supplementation did not result in elevation of plasma NAD + levels but resulted in a small increase in NAD + in the skin samples. NR supplementation did not prevent capsaicin‐induced degeneration of the epidermal sensory nerve fibers, and there was no difference in the amount of epidermal reinnervation at the 90‐day visit. Although there was a small but statistically significant increase in the number of epidermal sensory nerve fibers at the 60‐day visit, these results are preliminary and will need to be validated in larger studies. Interpretation At present oral NR supplementation, at the doses used in this study, cannot be recommended to prevent neuropathy or to improve nerve regeneration.