Nicotinamide Riboside Did Not Slow Early Parkinson Disease in a 410-Patient JAMA Trial. Scores Were Slightly Worse.
In the 52-week NOPARK trial at 11 Norwegian centers, MDS-UPDRS parts I to III rose 2.72 points more with the over-the-counter supplement than with placebo (P = .02). It is the evidence to cite when patients ask about NAD boosters.
Idea in Brief
The Trial
NOPARK randomized 410 adults with Parkinson disease diagnosed within two years to nicotinamide riboside 500 mg twice daily or placebo for 52 weeks at 11 centers in Norway.
The Result
MDS-UPDRS parts I to III rose 2.45 points with the supplement and fell 0.27 with placebo, an adjusted difference of 2.72 points favoring placebo (P = .02). Nonmotor scores were also worse.
Why It Matters
The authors say the findings do not support nicotinamide riboside as a disease-modifying treatment. Patients can buy it over the counter, so ask whether they already take it.
Nicotinamide riboside, an over-the-counter precursor of nicotinamide adenine dinucleotide (NAD), did not slow early Parkinson disease in a randomized trial, called NOPARK, published Oct. 8 in JAMA. Patients who took it scored slightly worse on the primary motor and nonmotor measure than patients who took placebo.
NAD-boosting supplements are sold without a prescription, and patients with a new diagnosis may ask whether to start one. This trial is a placebo-controlled phase 3 test of that idea, and its result points the other way. The authors, led by Brage Brakedal, PhD, wrote that the findings do not support nicotinamide riboside as a disease-modifying treatment.
What the trial showed
The trial was randomized, double-blind and placebo-controlled, at 11 centers in Norway. Of 537 patients screened, 410 were randomized between May 2020 and June 2024, and 393 were in the primary analysis. Patients were 35 or older, had been diagnosed within the prior two years, were Hoehn and Yahr stage below 3, had an abnormal dopamine transporter scan and were on stable dopaminergic treatment. Mean age was 65.6 years, and 34 percent were women.
Participants took nicotinamide riboside 500 mg twice daily (n = 206) or matching placebo (n = 204) for 52 weeks. The primary outcome was change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) parts I through III at week 52, where a higher score is worse.
The score rose by 2.45 points (95% CI, 0.80 to 4.10) with nicotinamide riboside and fell by 0.27 points (95% CI, minus 1.95 to 1.40) with placebo. The adjusted difference was 2.72 points (95% CI, 0.47 to 4.98; P = .02), favoring placebo.
A negative trial of an inexpensive supplement is still useful. It gives you evidence to cite when a patient asks whether to add it.
Secondary outcomes and safety
Of five prespecified secondary outcomes, which included MDS-UPDRS parts I, II and III separately, dopamine transporter imaging and the Non-Motor Symptoms Scale (NMSS), four showed no significant difference between groups. The NMSS was the exception: nonmotor burden was higher with nicotinamide riboside, by an adjusted 4.22 points (95% CI, 1.07 to 7.37; P = .009).
Serious adverse events were reported in 17 of 205 patients (8.3 percent) in the nicotinamide riboside group and 29 of 205 (14.1 percent) in the placebo group. The safety counts use 205 per group, slightly different from the 206 and 204 randomized, and the abstract does not explain the difference or list the causes of the serious events. Brain imaging showed no sign that the supplement slowed or sped up the loss of dopamine transporter signal, according to the University of Bergen.
"NR clearly increased NAD metabolism, but this did not translate into clinical improvement," Charalampos Tzoulis, MD, PhD, who led the study at Haukeland University Hospital and the University of Bergen, told Inside Precision Medicine.
Clinical Pearls
- Population: age 35 or older, diagnosis within two years, Hoehn and Yahr stage below 3, abnormal dopamine transporter scan, stable dopaminergic treatment.
- Dose tested: nicotinamide riboside 500 mg twice daily for 52 weeks, against matching placebo.
- Primary outcome: adjusted difference of 2.72 MDS-UPDRS points (95% CI, 0.47 to 4.98) in favor of placebo.
- Non-Motor Symptoms Scale: adjusted difference of 4.22 points (95% CI, 1.07 to 7.37) in favor of placebo.
- Serious adverse events: 8.3 percent with the supplement, 14.1 percent with placebo.
- The trial does not address longer exposure, other doses or other NAD precursors.
How far the result goes
The finding is one trial at one year in patients already on dopaminergic therapy, so it cannot speak to longer exposure, different doses or other NAD precursors. The score rose with the supplement while it stayed roughly flat with placebo, and the lower bound of the confidence interval on the difference is 0.47 points, so the size of the harm is uncertain. The University of Bergen described the difference as modest and below the usual threshold for clinically relevant worsening in an individual patient. The trial is registered at ClinicalTrials.gov as NCT03568968. Haukeland University Hospital sponsored it, and the University of Bergen lists funding from the Research Council of Norway, the Kristian Gerhard Jebsen Foundation, Helse Vest and KlinBeForsk. ChromaDex, now Niagen Bioscience, which sells nicotinamide riboside, supplied the capsules and placebo; the university says no supporting institution had a role in the design, analysis or decision to publish.
The result also arrives as disease-modifying options are still being sought. For the symptomatic side of the pipeline, see our coverage of tavapadon and the D1/D5 agonists.
What it means in clinic
When a patient with early Parkinson disease asks about nicotinamide riboside, you can now point to a randomized trial with a negative primary result and a signal toward worse nonmotor scores. Ask whether they already take it, since it is sold without a prescription, and add it to the medication and supplement list. If they want to stay on it, the trial gives no basis for expecting benefit. Enrollment in a registered trial is a better route for patients who want to pursue a disease-modifying approach.
Reported, fact-checked and edited by The Script Pad's editorial staff.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
