TL;DR
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A phase III trial found that nicotinamide riboside did not improve clinical outcomes in people with early Parkinson’s disease over 52 weeks. Scores worsened modestly more in the supplement group than in the placebo group, despite clear increases in blood NAD levels.
A phase III trial of 410 people found that nicotinamide riboside, an over-the-counter supplement marketed for longevity, did not improve clinical outcomes in early Parkinson’s disease over 52 weeks. Participants taking the supplement had a modestly greater worsening in movement and daily-living scores than those receiving placebo, according to results from the NOPARK trial published in JAMA.
The trial’s primary measure was the change in total Movement Disorder Society Unified Parkinson Disease Rating Scale scores, which include a motor examination and patients’ experiences of daily living. At week 52, scores worsened by an average of 2.45 points in the nicotinamide riboside group; the placebo group’s scores trended toward improvement. The adjusted mean difference between groups was 2.72 points (95% CI 0.47 to 4.98; P=0.02).
Nonmotor symptom burden also worsened more in the supplement group. Researchers found no significant difference between groups in changes to cognitive test scores, and brain imaging showed no evidence of slowed or accelerated change in the dopamine system. The study did find lower EuroQol-5D-5L quality-of-life index values in the supplement group.
Nicotinamide riboside did raise NAD levels in participants’ blood: at week 52, the between-group difference in total blood NAD was 30.00 micromoles per liter. That biological effect did not correspond to clinical improvement. Serious adverse events were reported in 8.3% of supplement recipients and 14.1% of placebo recipients; the researchers said most adverse events were considered unrelated or unlikely to be related to treatment. One participant in the supplement group experienced cardiac arrest and died.
What the Results Mean for Parkinson’s
The findings do not support using nicotinamide riboside to slow Parkinson’s disease, the researchers said. That conclusion matters because the supplement is widely available without a prescription and has been promoted as a way to raise NAD, a molecule involved in cellular energy metabolism and other processes.
The results also distinguish a measurable biological change from a demonstrated health benefit: NAD levels increased, but clinical outcomes did not improve. The average difference in the primary score was modest and below commonly cited thresholds for a minimum clinically important difference. However, the investigators said the direction of results across clinical measures, sensitivity analyses and prespecified subgroups supported their overall finding.
The trial does not establish that nicotinamide riboside worsens Parkinson’s disease or that the results apply to every user or stage of illness. It tested a defined dose over one year in people with early disease who were receiving stable dopaminergic treatment. People considering supplements for a medical condition should discuss them with a qualified health professional.
NAD supplement for Parkinson's disease
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How NOPARK Tested NAD Supplementation
Nicotinamide riboside is a form of vitamin B3 and a precursor the body can use to produce NAD+. Animal research and smaller human studies had suggested that raising NAD might help in Parkinson’s, prompting the larger NOPARK study. The phase III trial was described by lead investigator Charalampos Tzoulis as the largest study to date of an NAD-boosting treatment in a neurologic disorder.
Researchers randomized participants at 11 centers in Norway to take 500 milligrams of oral nicotinamide riboside twice daily or placebo for a year. Participants had received a Parkinson’s diagnosis within the previous two years, had early-stage disease and were on stable dopaminergic treatment. Median adherence to nicotinamide riboside was 99.6%.
The study population had a mean age of 66, and 66% were men. The trial excluded people with dementia, atypical parkinsonism, other neurodegenerative disorders or recent high-dose vitamin B3 use. Those limits matter when interpreting how well the results apply beyond the group studied.
“Nicotinamide riboside clearly increased NAD metabolism, but this did not translate into clinical improvement.”
— Charalampos Tzoulis, lead investigator, in a statement
Why Scores Diverged From Placebo
The trial shows an association between assignment to nicotinamide riboside and modestly worse scores on the primary measure, but it does not establish why the groups differed. The researchers suggested sustained NAD augmentation might have unfavorable effects in Parkinson’s biology, or that the supplement could interact with dopaminergic treatment. Both remain possibilities requiring further study.
The placebo group’s lack of apparent disease progression may partly reflect the effects of dopaminergic therapy, the authors said. The trial also had no washout phase, limiting the ability to separate treatment effects, and dopamine-transporter imaging may not be sensitive enough to detect subtle changes over one year. The study therefore does not resolve how nicotinamide riboside might affect longer-term disease progression or people not represented in the trial.
Further NAD Studies Are Planned
Nicotinamide riboside is still being studied in clinical research. Supplement maker Niagen Bioscience has announced plans for a large randomized, placebo-controlled trial with Mass General Brigham to examine healthy-aging outcomes and related biomarkers. That planned study addresses a different research question from NOPARK and does not change the Parkinson’s trial results.
For Parkinson’s disease, the immediate next step is for researchers and clinicians to interpret the findings alongside other evidence. The NOPARK report does not provide proof of benefit for the supplement in early Parkinson’s, and further studies would be needed to clarify the possible reasons for the score differences, longer-term effects and relevance to other patient groups.
Key Questions
Did nicotinamide riboside slow Parkinson’s disease in the trial?
No clinical benefit was found over 52 weeks. The supplement group’s primary Parkinson’s rating scores worsened modestly more than those in the placebo group.
What was the primary outcome?
The primary outcome was change in total MDS-UPDRS score, a measure combining a motor examination with patients’ experiences of daily living.
Did the supplement raise NAD levels?
Yes. Blood NAD levels increased in the nicotinamide riboside group, but that change did not translate into clinical improvement in the trial.
Does the study prove nicotinamide riboside makes Parkinson’s worse?
No. It found modestly worse average outcomes in the supplement group compared with placebo, but it did not establish the cause or prove that the supplement worsens the disease. The authors said possible explanations remain uncertain.
Who took part in the NOPARK trial?
The study enrolled 410 people with early Parkinson’s at 11 Norwegian centers. Participants were assigned to nicotinamide riboside or placebo for one year and were receiving stable dopaminergic treatment.
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