Objective:

To evaluate the efficacy and safety of nicotinamide adenine dinucleotide (NAD⁺), NADH, and NAD⁺ precursors in improving motor and non-motor symptoms in Parkinson’s disease (PD).

Background:

Mitochondrial dysfunction and reduced NAD⁺ levels contribute to Parkinson’s disease pathogenesis by modified energy metabolism, oxidative stress, and neuronal loss. NAD⁺ and its precursors—such as nicotinamide riboside and niacin—may restore mitochondrial bioenergetics and mitigate disease progression.

Design/Methods:

A systematic review and meta-analysis were done in accordance with PRISMA and Cochrane guidelines. PubMed, Scopus, and Web of Science were searched from inception through March 2025. Studies evaluating NAD⁺, NADH, or NAD⁺ precursors in PD were included. Twelve studies met inclusion criteria; four randomized controlled trials (n = 136) were pooled quantitatively. Primary outcomes were changes in motor performance (UPDRS III, MDS-UPDRS III) and disease severity (Hoehn and Yahr scale). Data were synthesized using the DerSimonian–Laird random-effects model.

Results:

Nicotinamide riboside demonstrated a non-significant trend toward motor improvement compared with placebo (mean difference = –4.49, 95% CI [–11.01, 2.04]; p = 0.18; I² = 24%). Niacin supplementation yielded a similar trend (mean difference = –0.91, 95% CI [–4.21, 2.38]; p = 0.59). The pooled change in Hoehn and Yahr stage favored treatment (mean difference = –0.047; p = 0.739; I² = 0%). Adverse events were comparable and mild  between groups, with fewer reports of headache and nausea in treatment arms.

Conclusions:

Although statistical significance was not recognized, NAD⁺ and its precursors showed consistent trends toward improved motor outcomes and favorable tolerability in PD. These results support the potential of NAD⁺-based interventions as safe, mitochondria-targeted adjunct therapies and highlight the need for larger, long-term randomized trials to confirm efficacy of the treatment.