TL;DR
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The phase III NOPARK trial found that nicotinamide riboside did not improve the primary clinical measure in people with early Parkinson’s disease over 52 weeks. Participants taking the supplement had modestly worse scores than those receiving placebo, although researchers said the trial does not explain why and did not show that the supplement caused the difference.
A phase III trial found that nicotinamide riboside, an over-the-counter supplement marketed for longevity, did not improve clinical outcomes in people with early Parkinson’s disease over 52 weeks. The 410-participant NOPARK study instead found modestly worse scores on its primary measure among those taking the supplement than among those receiving placebo, despite a clear rise in blood NAD levels.
The randomized trial compared 500 milligrams of nicotinamide riboside twice daily with placebo for one year. Participants had been diagnosed with Parkinson’s within the previous two years and were receiving stable dopaminergic treatment. The study enrolled patients at 11 centers in Norway; 206 were assigned the supplement and 204 placebo.
The primary outcome was change in the Movement Disorder Society Unified Parkinson Disease Rating Scale, or MDS-UPDRS, which measures motor symptoms and patients’ experiences of daily living. At week 52, scores in the supplement group had worsened by an average of 2.45 points. The placebo group’s scores trended toward improvement, producing an adjusted between-group difference of 2.72 points (95% confidence interval 0.47 to 4.98; P=0.02), according to the trial report in JAMA.
The supplement raised total blood NAD compared with placebo, with a between-group difference of 30.00 micromoles per liter at week 52. But this biological change was not accompanied by clinical improvement. Nonmotor symptom burden also worsened more in the supplement group. Researchers found no significant difference in changes on a cognitive screening measure and no imaging evidence that the treatment slowed or accelerated changes in the dopamine system.
A Biomarker Rise Without Clinical Benefit
The results challenge the idea that increasing NAD, a molecule involved in cellular energy metabolism and DNA repair, will by itself slow Parkinson’s progression. Nicotinamide riboside is widely available as a supplement, and the trial tested whether its effects on NAD would translate into a measurable benefit for people with the disease. In this study, blood NAD increased, but the primary clinical outcome did not improve.
The observed difference was described by the researchers as modest and below commonly cited thresholds for a minimum clinically important difference. They also said that the pattern across clinical outcomes and analyses supported the reliability of the overall result. That does not establish that the supplement worsens Parkinson’s disease: the trial compared groups over one year and cannot, on its own, explain the reasons for the difference.
The safety findings also require careful reading. Serious adverse events occurred in 8.3% of participants taking nicotinamide riboside and 14.1% of those receiving placebo. Most adverse events were considered unrelated or unlikely to be related to treatment. One participant in the supplement group experienced cardiac arrest and died; the report does not establish that the supplement caused the death.
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Why Researchers Tested NAD Boosting
Nicotinamide riboside is a form of vitamin B3 and a precursor the body can use to raise NAD+, the active form of NAD involved in cellular processes. Animal research and smaller human studies had suggested that boosting NAD might help in Parkinson’s disease, providing the biological rationale for a larger clinical test.
NOPARK was described by the researchers as the largest trial to date of an NAD-boosting treatment in a neurologic disorder. Its participants had early disease, a mean age of 66, and stable dopamine-related treatment. People with dementia, atypical parkinsonism, other neurodegenerative disorders or recent high-dose vitamin B3 use were excluded. Adherence to the assigned supplement was high, with median adherence reported at 99.6%.
The trial’s placebo group did not show the expected decline during the study, which the researchers said may partly reflect the effects of dopaminergic treatment. They also acknowledged that the study had no washout phase and that dopamine transporter imaging has limited sensitivity for detecting subtle changes over one year.
“Nicotinamide riboside clearly increased NAD metabolism, but this did not translate into clinical improvement.”
— Charalampos Tzoulis, trial investigator, in a statement
Why Scores Diverged From Placebo
The study does not establish why the nicotinamide riboside group had worse average scores than the placebo group. The researchers said possible explanations include an unfavorable biological effect that is not yet understood or an interaction with dopaminergic treatment; these remain hypotheses, not proven mechanisms. The absence of a washout phase also limits how researchers can interpret treatment-related changes.
The trial ran for one year and enrolled people with early Parkinson’s who met specific eligibility criteria, so its findings do not settle the supplement’s effects in other groups or over longer periods. Imaging did not show a difference in dopamine-system change, but the authors noted that the imaging method has limited sensitivity to subtle changes over this timeframe. The findings also do not establish that the supplement caused the cardiac arrest and death reported in one participant.
Further NAD Trials Remain Planned
Nicotinamide riboside is still being studied. 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 proposed study has a different focus from NOPARK and, based on the available report, is not a further test of Parkinson’s disease progression.
For Parkinson’s specifically, the NOPARK investigators’ results leave open questions about the reasons for the clinical-score difference and whether findings would hold over a longer period or in other patient groups. The reported evidence does not support using nicotinamide riboside to slow early Parkinson’s disease. Details of any additional Parkinson’s trials or follow-up analyses were not provided in the source report.
Key Questions
Did nicotinamide riboside slow Parkinson’s disease in the trial?
No clinical benefit was found on the primary measure over 52 weeks. The supplement group’s scores worsened modestly compared with the placebo group.
Did the supplement change NAD levels?
Yes. The trial found a higher total blood NAD level in the supplement group than in the placebo group at week 52, with a reported between-group difference of 30.00 micromoles per liter. That biological change did not translate into clinical improvement.
Does the trial show that nicotinamide riboside makes Parkinson’s worse?
No. The study found modestly worse average scores compared with placebo, but it did not determine why the groups differed or prove that the supplement caused the difference.
What serious adverse events were reported?
Serious adverse events occurred in 8.3% of the supplement group and 14.1% of the placebo group. One participant taking nicotinamide riboside had cardiac arrest and died; the report does not establish that the treatment caused the death.
Are more studies of nicotinamide riboside planned?
Niagen Bioscience has announced plans for a randomized trial with Mass General Brigham focused on healthy aging and related biomarkers. The source report did not describe a new Parkinson’s-specific trial.
Source: rss
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