Large NOPARK trial: nicotinamide riboside did not slow early Parkinson's disease

One of the largest and longest trials of an NAD+ precursor has reported a negative result. In the NOPARK trial, published in JAMA on October 8, 2026, people with early Parkinson’s disease who took nicotinamide riboside (NR) for 52 weeks did not do better than those given placebo. On the main clinical score they did slightly worse.

What the researchers did

NR is a derivative of vitamin B3 that raises levels of NAD+, a molecule that helps cells produce energy. NAD+ is reported to decline with age, which is one reason NR has attracted interest in aging research. Earlier, smaller studies in Parkinson’s disease had suggested NR could raise NAD levels and was generally tolerated, but whether this translated into clinical benefit was unclear.

The trial, led by Professor Charalampos Tzoulis at Haukeland University Hospital and the University of Bergen, was randomized, double-blind and placebo-controlled, and ran at 11 centers in Norway (ClinicalTrials.gov NCT03568968). Of 537 people screened, 410 were randomized between May 2020 and June 2024: 206 to NR at 500 mg twice daily and 204 to matching placebo, for 52 weeks. Participants were aged 35 or over, had been diagnosed with Parkinson’s disease in the previous two years, had brain imaging consistent with loss of dopamine-producing nerve cells, and were on stable dopaminergic treatment. The primary analysis included 393 people (mean age 65.6; 34% women). The main outcome was the change in the total MDS-UPDRS score (parts I to III), where higher scores mean worse disease.

What they found

At 52 weeks the total score rose by 2.45 points (95% CI 0.80 to 4.10) in the NR group and fell by 0.27 points (95% CI −1.95 to 1.40) with placebo. The adjusted difference was 2.72 points (95% CI 0.47 to 4.98; P = 0.02), in favor of placebo. The JAMA summary notes that the clinically important difference on this scale is 6.7 points for improvement and 5.2 for worsening, so the gap was smaller than those thresholds.

Four of five prespecified key secondary outcomes showed no significant difference. Non-motor symptoms, however, worsened more with NR (adjusted difference 4.22 points on the Non-Motor Symptoms Scale; 95% CI 1.07 to 7.37; P = 0.009). Serious adverse events were recorded in 17 of 205 people (8.3%) taking NR and 29 of 205 (14.1%) on placebo.

Medscape’s report on the trial, which we also read, adds that blood NAD levels were higher with NR than placebo, but that a brain-imaging marker of energy metabolism in a subset of 159 participants was similar between the groups, and dopamine-transporter imaging showed no measurable change. We have not independently checked these extra details against the full paper.

The authors concluded that the findings “do not support nicotinamide riboside as a disease-modifying treatment for Parkinson disease”.

What this means

The trial answers a specific question: does NR at this dose, added to standard medication, slow early Parkinson’s disease over a year? On this evidence, it did not. Professor Tzoulis told Medscape that NR produced a clear systemic metabolic response that did not translate into clinical benefit, and that he thought simply substituting another NAD precursor was unlikely to change the outcome. That is the investigator’s opinion, not a trial finding.

The study does not address other uses of NR or other NAD+ precursors, and it did not test people without Parkinson’s disease. It is nonetheless a reminder that raising a biomarker such as blood NAD does not by itself show a clinical effect.

Limits of the evidence

• Specific population. Everyone had early Parkinson’s disease and was taking standard dopaminergic medication, so the results cannot be applied to healthy people or other conditions.
• One dose, one year. The trial tested 500 mg twice daily for 52 weeks. Longer or different regimens were not studied.
• Design limits noted in coverage. Medscape reports that participants were assessed while on their usual medication, with no washout period to separate symptom relief from effects on disease progression, and that imaging may be insensitive to small changes over one year.
• Statistical context. The primary difference (P = 0.02) was modest and below the clinically important thresholds.
• What we read: the JAMA key points and abstract text, the JAMA press release, the ClinicalTrials.gov entry and Medscape’s coverage. The JAMA full-text page could not be loaded, so we have not reviewed the funding statement, conflict-of-interest disclosures or the full methods.

Sources

• Tzoulis 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 (JAMA Network)
• JAMA Network media release, October 8, 2026: Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease
• Trial registry: ClinicalTrials.gov NCT03568968
• Secondary coverage: Borreli L. Healthy Aging Supplement Fails in Large Parkinson’s Disease Trial. Medscape Medical News, October 27, 2026.

This article is for information only and is not medical advice. Speak to a healthcare professional before changing medication or supplements.