A randomized Phase III trial published in JAMA on October 8, 2026, found that nicotinamide riboside, an oral precursor of nicotinamide adenine dinucleotide (NAD+), failed to improve outcomes in early Parkinson disease and was associated with modest but statistically significant worsening of clinical scores compared with placebo. The NOPARK study was conducted by Norwegian researchers, including a team from the University of Bergen and Haukeland University Hospital, and challenges the hypothesis that boosting NAD+ levels could slow neurodegeneration.
The trial enrolled 410 participants with early Parkinson disease across 11 centers in Norway, randomizing them to nicotinamide riboside 500 mg twice daily or placebo for 52 weeks. The primary endpoint was change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) parts I–III total score, with higher scores indicating greater disease severity.
At Week 52, MDS-UPDRS scores increased by an adjusted mean of 2.45 points in the nicotinamide riboside group and decreased by 0.27 points with placebo, a difference of 2.72 points favoring placebo (95% CI 0.47–4.98; P=.02). Nonmotor symptoms also worsened significantly more with nicotinamide riboside (adjusted mean difference 4.22 points; P=.009), while four other prespecified key secondary outcomes, including dopamine transporter imaging, showed no significant differences. The primary endpoint difference was below the threshold generally considered clinically important.
Serious adverse events occurred in 17 of 205 participants (8.3%) receiving nicotinamide riboside and 29 of 205 (14.1%) receiving placebo. The investigators did not establish that nicotinamide riboside accelerated the underlying neurodegenerative process despite the observed worsening in clinical scores.
Nicotinamide riboside had been investigated as a potential disease-modifying treatment because NAD+ supports mitochondrial function and other cellular processes implicated in Parkinson disease. Earlier research by the Bergen investigators, including the 2022 Phase I NADPARK study, found that nicotinamide riboside increased cerebral NAD levels after 30 days and produced exploratory signals of clinical benefit, providing the rationale for larger-scale testing.