Design: Phase 3, randomised, double-blind, placebo-controlled, 11 centres
Population: 410 adults with Parkinson disease diagnosed within 2 years, Hoehn and Yahr stage <3
Primary outcome: Change in total MDS-UPDRS (parts I–III) at 52 weeks
Effect: Adjusted difference 2.72 points (95% CI 0.47–4.98) favouring placebo

NOPARK randomised 410 people with Parkinson disease diagnosed within the previous two years, confirmed on dopamine transporter imaging, to nicotinamide riboside 500 mg twice daily or placebo for 52 weeks at 11 Norwegian centres. The supplement, a precursor of NAD, had been proposed as disease-modifying on the strength of preclinical and early clinical work.

Total MDS-UPDRS rose by 2.45 points on nicotinamide riboside and fell slightly on placebo, a difference of 2.72 points (95% CI 0.47–4.98) favouring placebo. Non-motor symptom burden also worsened more on the supplement. Serious adverse events were less frequent on nicotinamide riboside (8.3% vs 14.1%).

The harm signal is small: the difference sits below the roughly 5-point change usually treated as clinically meaningful. But a phase 3 trial with no benefit and a small signal in the wrong direction is a clear answer. Patients buying NAD precursors online for neuroprotection can be told the best trial so far found nothing to support it.

Advise patients with Parkinson disease that nicotinamide riboside did not slow progression in a phase 3 trial.
Ask about over-the-counter supplements at review, since NAD precursors are widely marketed for neuroprotection.
Keep exercise and standard dopaminergic therapy as the core of early management.
Offer trial enrolment to patients who want a disease-modifying option.

Why it matters

A widely sold supplement has now had its definitive test and failed it.

The statistics, in plain English

The 2.72-point difference is statistically significant but smaller than the 5.2-point worsening generally considered noticeable to patients, so the clearest message is the absence of benefit rather than meaningful harm.