TL;DR
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The phase III NOPARK trial found no clinical benefit from nicotinamide riboside, an over-the-counter supplement marketed for longevity, in people with early Parkinson’s disease. Participants taking it had modestly worse scores on the trial’s main measure than those taking placebo, although the reasons for that difference remain unknown.
A phase III trial found that nicotinamide riboside, a vitamin B3 form sold as an over-the-counter longevity supplement, did not improve outcomes in people with early Parkinson’s disease and was associated with modestly worse scores than placebo over 52 weeks. The NOPARK study’s results, reported in JAMA, do not support using the supplement to slow Parkinson’s progression.
The trial randomized 410 people at 11 centers in Norway to take nicotinamide riboside or placebo for one year. The treatment group received 500 milligrams twice daily. Participants had been diagnosed within the previous two years, and their Parkinson’s treatment was stable at enrollment. Median adherence to nicotinamide riboside was 99.6%.
The primary outcome was change in the Movement Disorder Society Unified Parkinson Disease Rating Scale, or MDS-UPDRS, which combines a motor examination with measures of patients’ daily experiences. 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; the adjusted difference between groups was 2.72 points (95% confidence interval 0.47 to 4.98; P=0.02).
Researchers also reported greater worsening in nonmotor symptom burden in the supplement group. There was no significant difference in changes in cognitive test scores, and dopamine-system imaging did not show that the supplement slowed or accelerated change. Blood tests showed that nicotinamide riboside raised NAD levels, but that biological change did not correspond to clinical improvement.
What the Results Mean for Supplement Users
The results matter because nicotinamide riboside is widely sold without a prescription and promoted for its effects on NAD metabolism, a process involved in cellular energy production and repair. The trial tested whether raising NAD could help delay Parkinson’s progression; its findings do not support that use in people with early disease.
The reported difference in the main clinical score was modest and below commonly cited thresholds for a minimum clinically important difference, the researchers said. That does not turn the result into evidence of benefit: the trial did not meet its goal of showing improvement, and several clinical measures pointed in an unfavorable direction. It also does not establish that the supplement caused harm or that it worsens Parkinson’s in every patient.
For people considering the supplement, the findings are a reason to discuss its use with a qualified health professional, particularly alongside Parkinson’s medicines. The study does not justify replacing prescribed treatment with a supplement, and it does not settle whether nicotinamide riboside has effects in other populations or for other purposes.
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Why Researchers Tested NAD Boosting
Nicotinamide riboside is a precursor to NAD+, a molecule used in cellular energy metabolism, DNA repair and inflammation regulation. Animal research and smaller human studies had suggested that raising NAD might help in Parkinson’s disease, prompting a larger test of the approach.
NOPARK enrolled people with relatively early disease: participants had a diagnosis within two years, a Hoehn and Yahr stage below 3, and confirmatory dopamine-transporter imaging. People with dementia, atypical parkinsonism, other neurodegenerative disorders, or recent high-dose vitamin B3 use were excluded. The findings therefore apply most directly to a selected group with early Parkinson’s, rather than all people with the condition.
The researchers described NOPARK as the largest trial of an NAD-boosting treatment in a neurological disorder to date. The placebo group did not show the expected degree of progression during the year, which the investigators said may partly reflect participants’ dopaminergic treatment.
“Nicotinamide riboside clearly increased NAD metabolism, but this did not translate into clinical improvement.”
— Charalampos Tzoulis, study author, in a statement
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Why Scores Worsened Remains Unknown
The trial established an association between assignment to nicotinamide riboside and worse average clinical scores relative to placebo, but it did not determine why the difference occurred. The researchers suggested possible explanations, including an unfavorable biological effect in Parkinson’s disease or an interaction with dopaminergic medication. These are hypotheses, not findings the study proved.
The study also had limitations. It did not include a washout phase, so the results do not show whether the score difference would persist after treatment stopped. The investigators said dopamine-transporter imaging has limited sensitivity for detecting subtle changes over one year. The placebo group’s limited progression may also have made it harder to assess whether the supplement affected the disease’s course.
Serious adverse events were reported in 8.3% of the nicotinamide riboside group and 14.1% of the placebo group. Hypertension was the most common adverse event in both groups, and most reported events were considered unrelated or unlikely to be related to treatment. One participant in the supplement group had cardiac arrest and died; the supplied report does not establish that the supplement caused the death.
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Further Trials Will Test NAD Treatments
Nicotinamide riboside remains under investigation in clinical studies, but NOPARK does not support using it to slow Parkinson’s disease. Researchers and clinicians may look to further trials to clarify the treatment’s effects, including whether the observed score difference reflects the supplement itself, an interaction with standard medication, or another factor.
Niagen Bioscience has announced plans for a large randomized, placebo-controlled study with Mass General Brigham to examine healthy-aging outcomes and related biomarkers. That planned study is not a Parkinson’s trial, and its results will not answer the disease-specific questions raised by NOPARK. No follow-up date or new Parkinson’s trial milestone was specified in the source report.
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Key Questions
Did nicotinamide riboside slow Parkinson’s disease in the trial?
No. The phase III NOPARK trial found no clinical benefit over 52 weeks in participants with early Parkinson’s disease. The supplement group had modestly worse average scores on the primary outcome than the placebo group.
What dose did participants take?
Participants assigned to treatment took 500 milligrams twice daily for one year. The study enrolled 410 people across 11 Norwegian centers.
Does the trial prove the supplement worsens Parkinson’s?
No. The trial found worse average scores in the supplement group relative to placebo, but it did not establish why that difference occurred or prove the supplement caused it. Researchers raised possible explanations, including a medication interaction, as hypotheses.
Did nicotinamide riboside raise NAD levels?
Yes. Blood tests showed that the supplement increased NAD measures, but that change did not translate into clinical improvement in the trial.
Is another study of nicotinamide riboside planned?
Niagen Bioscience has announced plans for a randomized study with Mass General Brigham on healthy-aging outcomes and related biomarkers. The source report did not specify a start date, and that planned study is not focused on Parkinson’s disease.
Source: rss
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