Early Parkinson Scores Worsened Slightly More With Nicotinamide Riboside Than Placebo

Oral nicotinamide riboside did not improve clinical outcomes in patients with early Parkinson disease and was associated with worse outcomes than placebo, according to results of the phase 3 NOPARK randomized clinical trial published in JAMA.

Nicotinamide riboside, an oral precursor of nicotinamide adenine dinucleotide, has been proposed as a potential disease-modifying therapy for Parkinson disease based on preclinical and early studies. According to the investigators, whether prolonged oral treatment improves clinical outcomes in the disease had been unknown.

The double-blind, placebo-controlled trial was conducted at 11 centers in Norway. Eligible patients were aged 35 years or older, had been diagnosed with Parkinson disease within 2 years before enrollment, had Hoehn and Yahr stage less than 3 and abnormal dopamine transporter scintigraphy findings, and were receiving stable dopaminergic treatment. Patients were randomized to nicotinamide riboside 500mg twice daily (n = 206) or matching placebo (n = 204) for 52 weeks. Among the 393 patients in the primary analysis, mean age was 65.6 years and 34% were female.

The primary outcome was change from baseline to week 52 in the Movement Disorder Society Unified Parkinson Disease Rating Scale total score (parts I-III), on which higher scores indicate more severe disease. Scores increased by 2.45 points with nicotinamide riboside and decreased by 0.27 points with placebo, an adjusted mean difference of 2.72 points favoring placebo (95% CI, 0.47-4.98; P = 0.02). The trial specified a clinically important difference for worsening of 5.2 points. Four of 5 key secondary outcomes showed no significant difference between groups, but nonmotor symptom burden on the Non-Motor Symptoms Scale worsened more with nicotinamide riboside (adjusted mean difference, 4.22 points; P = 0.009).

In the safety population, serious adverse events occurred in 17 of 205 patients (8.3%) receiving nicotinamide riboside and 29 of 205 (14.1%) receiving placebo. The investigators concluded that 52 weeks of nicotinamide riboside did not improve clinical outcomes in early Parkinson disease and that the findings do not support it as a disease-modifying treatment.

Source: Brakedal B, Skeie GO, Derad C, et al. Nicotinamide riboside for patients with early-stage Parkinson disease: the NOPARK randomized clinical trial. JAMA. Published online October 8, 2026. doi:10.1001/jama.2026.18828