NOPARK trial: Nicotinamide riboside shows no benefit for early Parkinson's

Results from a substantial randomized study indicate that nicotinamide riboside (NR) does not provide clinical benefits for patients with early Parkinson’s disease. The findings, published in JAMA, stem from the NOPARK trial, which involved 410 participants across Norway.

Trial design and participant allocation

Professor Charalampos Tzoulis led the investigation at Haukeland University Hospital and the University of Bergen. The study enrolled individuals at 11 Norwegian centers, randomly assigning them to receive either NR or a placebo over a one-year period. Neither the participants nor the research teams were aware of the specific treatment assignments during the trial.

Clinical outcomes and statistical analysis

Disease severity was assessed using the MDS-UPDRS scale, where higher scores reflect more severe symptoms. After 52 weeks, the group receiving NR experienced an average worsening of 2.45 points. In contrast, the placebo group showed essentially no change. The adjusted difference favored the placebo by 2.72 points. While this gap was statistically significant, it remained modest and fell below the threshold typically considered clinically important.

Biological rationale and imaging results

The trial tested NR because it increases cellular levels of nicotinamide adenine dinucleotide (NAD), a molecule vital for energy metabolism, DNA repair, and inflammation regulation. Preclinical studies and smaller trials had suggested that boosting NAD might protect nerve cells affected by Parkinson’s. However, brain imaging revealed no evidence that NR slowed or accelerated changes in the dopamine system. Adverse event rates were similar between the two groups.

Researcher commentary and future directions

“We had a strong biological rationale for testing this treatment, and earlier, smaller clinical studies had produced encouraging findings,” said Professor Tzoulis, the study director. “NR clearly increased NAD metabolism, but this did not translate into clinical improvement. Our results therefore do not support NR as a treatment to slow Parkinson's disease.”

The researchers advise against using NR or other NAD-boosting supplements outside controlled clinical settings for Parkinson’s patients. They note, however, that these findings do not rule out potential benefits for other diseases, which require separate evaluation. Tzoulis expressed gratitude to the participants and colleagues at all 11 centers for making the national study possible.

The team will continue analyzing data to understand the biological mechanisms behind the results and to determine if specific patient subgroups responded differently. These insights may guide future research and new treatment strategies.

Key facts about the NOPARK study

• NOPARK is the largest trial to date of an NAD-boosting treatment in a neurological disorder.
• Haukeland University Hospital sponsored and coordinated the study.
• Participants received 500 mg of NR twice daily or matching placebo for 52 weeks.