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

Jan 8, 2026Journal of the peripheral nervous system : JPNS

Nicotinamide Riboside may help prevent small nerve damage and support nerve regrowth

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Abstract

Nicotinamide riboside supplementation did not elevate plasma NAD levels but showed a small increase in NAD in skin samples.

Nicotinamide riboside is a precursor to NAD, which is associated with axon degeneration.
Oral supplementation of nicotinamide riboside did not prevent degeneration of sensory nerve fibers after capsaicin exposure.
No significant difference was observed in the amount of epidermal nerve fiber regrowth after 90 days.
There was a small, statistically significant increase in epidermal sensory nerve fibers at 60 days, though these findings are preliminary.
Current findings indicate that nicotinamide riboside supplementation cannot be recommended for preventing neuropathy or enhancing nerve regeneration.

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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 NADlevels are associated with axonal degeneration. Nicotinamide riboside (NR) is a safe and widely available pyridine-nucleoside form of vitamin B3 and is an NADprecursor. + + +

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 NADlevels but resulted in a small increase in NADin 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.

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

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