Nicotinamide Riboside Fails to Improve Outcomes in Early Parkinson's Disease: JAMA
Norway: Researchers have found in a 52-week study that nicotinamide riboside did not improve clinical outcomes in patients with early Parkinson's disease. Treatment was associated with worse clinical outcomes than placebo, indicating that nicotinamide riboside is not supported as a disease-modifying therapy for Parkinson’s disease.
The phase 3 randomized clinical trial, published in JAMA, was conducted by Brage Brakedal of the Neuro-SysMed Center for Clinical Treatment Research, Department of Neurology, Haukeland University Hospital, Bergen, Norway, and colleagues. The study evaluated whether nicotinamide riboside, an oral precursor of nicotinamide adenine dinucleotide (NAD), could slow disease progression in patients with early-stage Parkinson’s disease.
Parkinson’s disease is a progressive neurological disorder characterised by motor and nonmotor symptoms. Although available treatments help manage symptoms, they do not stop the underlying disease progression. Nicotinamide riboside has attracted research interest because of its potential to increase NAD levels and its promising biological effects in earlier studies.
The trial enrolled 410 patients aged 35 years or older across 11 centres in Norway. Participants had received a Parkinson’s disease diagnosis within the preceding two years, had early-stage disease, and were on stable dopaminergic treatment. They were randomly assigned to receive either oral nicotinamide riboside 500 mg twice daily or a matching placebo for 52 weeks. The primary analysis included 393 participants, with a mean age of 65.6 years.
The primary outcome was the change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) score, which measures motor and nonmotor symptoms. Higher scores indicate greater disease severity.
The key findings were:
- Worsening clinical scores: At week 52, the MDS-UPDRS score increased by 2.45 points in the nicotinamide riboside group, compared with a 0.27-point decrease in the placebo group.
- Significant difference favouring placebo: The adjusted mean difference between the groups was 2.72 points, indicating poorer clinical outcomes with nicotinamide riboside.
- Greater nonmotor symptom burden: The nicotinamide riboside group experienced a greater worsening in nonmotor symptoms, with an adjusted mean difference of 4.22 points on the Non-Motor Symptoms Scale.
- No consistent benefit across secondary outcomes: Four of the five prespecified secondary outcomes showed no statistically significant differences between the groups.
- Serious adverse events: These occurred in 8.3% of participants receiving nicotinamide riboside and 14.1% of those receiving placebo.
The findings indicate that nicotinamide riboside did not provide clinical benefits over one year and was associated with modestly worse outcomes on the primary measure. Although serious adverse events were less frequent in the treatment group, this did not translate into improved clinical outcomes.
The researchers concluded that the results do not support nicotinamide riboside as a disease-modifying treatment for early Parkinson’s disease. Further research is needed to identify therapies that can meaningfully slow disease progression rather than merely address symptoms.
Reference:
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 08, 2026. doi:10.1001/jama.2026.18828
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