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The phase III NOPARK trial found no clinical benefit from nicotinamide riboside in people with early Parkinson’s disease after 52 weeks. Participants assigned the supplement had modestly worse scores on the primary measure than those given placebo, despite clear increases in blood NAD levels.
A phase III trial of nicotinamide riboside, an over-the-counter supplement promoted for boosting cellular NAD+, found no clinical benefit in early Parkinson’s disease and modestly worse results than placebo on the main disease-rating measure after 52 weeks. The NOPARK findings, reported by researchers led by Charalampos Tzoulis of Haukeland University Hospital and the University of Bergen, bear on a supplement increasingly used for longevity and previously studied as a possible way to slow Parkinson’s progression.
The trial randomized 410 people at 11 centers in Norway to take either 500 milligrams of oral nicotinamide riboside twice daily or placebo for one year. Participants had been diagnosed with Parkinson’s within the previous two years. Median adherence to the supplement was 99.6%, according to the report.
The primary outcome was change from baseline in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), which covers motor symptoms and patients’ experiences of daily living. At week 52, the supplement group’s total scores worsened by an average of 2.45 points, while the placebo group’s scores trended toward improvement. The adjusted between-group difference was 2.72 points (95% confidence interval 0.47 to 4.98; P=0.02), favoring placebo.
The researchers also reported greater worsening of nonmotor symptom burden in the supplement group. There was no significant difference between groups in changes to Montreal Cognitive Assessment scores, and dopamine-transporter imaging showed no evidence that the supplement slowed or accelerated changes in the dopamine system over the study period. Blood tests did show that nicotinamide riboside increased NAD measures: at week 52, the between-group difference in total blood NAD was 30.00 micromoles per liter.
What the Trial Means for Supplement Users
The result separates a measurable biological effect from a demonstrated clinical benefit. Nicotinamide riboside raised blood NAD levels, but that change did not correspond to better Parkinson’s scores during the trial. The findings do not support using the supplement to slow Parkinson’s disease based on this study.
The result also matters because nicotinamide riboside is sold over the counter and marketed as a longevity supplement, while NAD-boosting treatments are being studied for several health goals. The trial was not a general test of longevity claims or every possible use of the supplement. It tested a particular dose, population and treatment period in early Parkinson’s disease.
The average difference on the primary measure was described by the researchers as modest and below commonly cited thresholds for a minimum clinically important difference. Still, they said the direction of findings across clinical outcomes and analyses supported the overall result. The study does not establish that the supplement caused lasting harm, but the worse scores argue against assuming that a plausible biological mechanism means a treatment will help patients.
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Why Researchers Tested NAD Boosting
Nicotinamide riboside is a form of vitamin B3 and a precursor to NAD+, a molecule involved in cellular energy metabolism, DNA repair and inflammation regulation. Animal research and smaller human studies had suggested that raising NAD-related measures might benefit people with Parkinson’s, providing the rationale for a larger test.
NOPARK is described in the report as the largest trial of an NAD-boosting treatment in a neurologic disorder to date. It enrolled people with early-stage disease, stable dopaminergic treatment and confirmatory dopamine-transporter imaging. The trial excluded people with dementia, atypical parkinsonism, other neurodegenerative disorders or recent high-dose vitamin B3 use, so its results do not directly cover those groups.
Participants received the supplement or placebo alongside their existing care for a year. The placebo group did not show the expected clear progression on the main measure, which the investigators said might partly reflect dopaminergic therapy. That feature and the lack of a washout period are relevant when interpreting the score difference, but do not change the reported finding that the supplement failed to improve the measured clinical outcome.
“Nicotinamide riboside clearly increased NAD metabolism, but this did not translate into clinical improvement.”
— Charalampos Tzoulis, lead investigator, in a statement
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What the One-Year Results Cannot Show
The study shows what happened to the measured outcomes over 52 weeks; it does not establish why the supplement group had worse scores or whether that difference would persist over a longer period. The researchers suggested that sustained NAD augmentation could have unfavorable effects in Parkinson’s biology, or that nicotinamide riboside might interact with dopaminergic treatment. These remain possible explanations, not confirmed causes.
The investigators also noted that the trial had no washout phase, and that dopamine-transporter imaging has limited sensitivity for detecting subtle changes over a year. Imaging therefore cannot settle whether the supplement affected underlying disease progression. The report also does not show that the findings apply to people without Parkinson’s or to other doses and treatment schedules.
Serious adverse events occurred in 8.3% of participants assigned nicotinamide riboside and 14.1% assigned placebo. Hypertension was the most common adverse event in both groups, and most 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 Other Uses
Nicotinamide riboside continues to be studied. The report says supplement maker Niagen Bioscience announced plans for a large randomized, placebo-controlled trial with Mass General Brigham to examine healthy-aging outcomes and related biomarkers. That planned study concerns a different research question from NOPARK and should not be treated as evidence that the supplement improves health or longevity.
For Parkinson’s disease, the NOPARK results provide a substantial test of the supplement at the studied dose and duration, but they do not explain the observed score difference or resolve every question about NAD-related treatments. Any further claims about disease slowing would need support from clinical outcomes in additional research. The immediate practical point from this trial is that nicotinamide riboside did not improve early Parkinson’s outcomes compared with placebo over one year.
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Key Questions
Did nicotinamide riboside slow Parkinson’s disease in the trial?
No. The NOPARK trial found no clinical benefit over 52 weeks. On the primary rating scale, the supplement group had modestly worse average results than the placebo group.
How many people took part in the study?
The trial randomized 410 people at 11 centers in Norway. Participants received 500 milligrams of nicotinamide riboside twice daily or placebo for one year.
Did the supplement affect NAD levels?
Yes. Blood tests showed a clear increase in NAD measures among participants taking nicotinamide riboside. That biological change did not translate into clinical improvement in the trial.
Did the trial prove that nicotinamide riboside caused harm?
No. The study found modestly worse Parkinson’s scores in the supplement group, but it did not establish why they worsened or prove a harmful mechanism. The researchers’ explanations, including a possible interaction with dopaminergic treatment, remain hypotheses.
Does this result apply to every use of nicotinamide riboside?
The trial tested early Parkinson’s disease, a specific dose and a one-year period. It does not answer whether nicotinamide riboside has effects in other populations or for other health goals, including the healthy-aging outcomes planned for a separate study.
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