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The phase III NOPARK trial found no clinical benefit from nicotinamide riboside, an over-the-counter supplement marketed to raise NAD+, in people with early Parkinson’s disease. At 52 weeks, overall symptom scores worsened more in the supplement group than in the placebo group, although the average difference was modest and its cause is unknown.
A phase III trial found that nicotinamide riboside, an over-the-counter supplement marketed to boost NAD+, did not improve clinical outcomes in people with early Parkinson’s disease. After 52 weeks, participants assigned the supplement had a greater average worsening in total Parkinson’s symptom scores than those given placebo, according to results from the 410-person NOPARK trial published in JAMA.
The trial’s primary measure was change in the Movement Disorder Society Unified Parkinson Disease Rating Scale, or MDS-UPDRS, which includes a motor examination and patients’ reports of daily-life symptoms. By week 52, scores in the nicotinamide riboside group had worsened by an average of 2.45 points. Placebo-group scores trended toward improvement, producing an adjusted mean difference of 2.72 points between groups (95% confidence interval 0.47 to 4.98; P=0.02).
The researchers also reported greater worsening in nonmotor symptom burden in the supplement group. There was no significant difference between groups in changes to Montreal Cognitive Assessment scores. Imaging showed no evidence that the treatment slowed or accelerated changes in the dopamine system over the study period.
The biological target did respond: at 52 weeks, blood NAD levels were higher in the supplement group, with a mean between-group difference of 30.00 micromoles per liter (P<0.001). However, raising NAD did not translate into clinical improvement. Serious adverse events were reported in 8.3% of participants receiving nicotinamide riboside and 14.1% receiving placebo. One participant in the supplement group had cardiac arrest and died; the report does not establish that the treatment caused the death.
Why the Trial Matters for Supplement Users
Nicotinamide riboside is sold without a prescription and promoted as a way to increase levels of NAD+, a molecule involved in cellular energy metabolism and other processes. The trial offers a large, controlled test of whether that biological rationale leads to better outcomes in Parkinson’s disease. In this study, the supplement raised blood NAD measures but did not improve symptoms, challenging the assumption that changing this biomarker will necessarily slow the disease.
The findings matter to people with Parkinson’s and clinicians weighing supplements alongside established care. They do not show that every use of nicotinamide riboside has the same effects, nor do they establish why scores worsened more in the treatment group. The difference in the primary outcome was described by the investigators as modest and below commonly cited thresholds for a minimum clinically important difference. Still, the result does not support using the supplement to slow Parkinson’s progression.
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How NOPARK Tested NAD Boosting
Researchers led by Charalampos Tzoulis of Haukeland University Hospital and the University of Bergen in Norway enrolled 410 people at 11 centers. Participants had been diagnosed with Parkinson’s within the previous two years, had relatively early-stage disease, and were receiving stable dopaminergic treatment. Their mean age was 66, and 66% were men.
Participants were assigned to take 500 milligrams twice daily of oral nicotinamide riboside or placebo for one year. The supplement group included 206 people and the placebo group 204; median adherence to nicotinamide riboside was 99.6%. Earlier animal research and smaller human studies had suggested possible benefit, helping motivate the larger phase III test. The authors described NOPARK as the largest trial to date of an NAD-boosting treatment in a neurologic disorder.
“Nicotinamide riboside clearly increased NAD metabolism, but this did not translate into clinical improvement.”
— Charalampos Tzoulis, trial lead, in a statement
Why Outcomes Were Worse Is Unknown
The trial establishes that the measured clinical outcomes did not favor nicotinamide riboside, but it does not explain why. The researchers suggested that sustained NAD augmentation might have unfavorable effects in Parkinson’s disease biology, or that the supplement could interact with dopaminergic medication and affect symptoms. Those are possible explanations, not findings proven by the study.
The placebo group’s scores did not show the progression the researchers might have expected; the authors said dopaminergic treatment could partly account for that pattern. The study also had no washout phase, and dopamine transporter imaging may be insufficiently sensitive to detect subtle changes over one year. The report does not establish whether the results apply to people with more advanced disease, to longer-term use, or to people taking the supplement for other reasons.
Further NAD Studies Remain Planned
Nicotinamide riboside is still being studied in other clinical settings. Niagen Bioscience has announced plans for a large randomized, placebo-controlled trial with Mass General Brigham focused on healthy-aging outcomes and related biomarkers. That planned study addresses a different research question and does not reverse the NOPARK result for Parkinson’s disease.
Further work would be needed to test the possible explanations raised by the researchers, including whether medication interactions or sustained NAD changes affected symptoms. Until more evidence is available, the NOPARK findings do not support nicotinamide riboside as a treatment to slow early Parkinson’s disease.
Key Questions
Did nicotinamide riboside slow Parkinson’s disease in the trial?
No. The 52-week NOPARK trial found no clinical benefit. The primary symptom scores worsened more on average in the supplement group than in the placebo group.
Did the supplement raise NAD levels?
Yes. The researchers reported higher blood NAD levels in the nicotinamide riboside group, including a 30.00 micromoles per liter mean difference between groups at week 52. That change did not correspond to clinical improvement.
Does the trial prove nicotinamide riboside caused worse symptoms?
The randomized trial found worse average outcomes on the primary measure in the supplement group, but it did not determine the reason. The authors raised possible biological effects or an interaction with Parkinson’s medication; these explanations remain unconfirmed.
Were serious adverse events more common with the supplement?
Serious adverse events occurred in 8.3% of the supplement group and 14.1% of the placebo group. One participant taking nicotinamide riboside died after cardiac arrest, but the report does not establish that the supplement caused the death.
Source: rss
