A dietary supplement widely marketed for healthy aging failed its biggest test yet as a Parkinson's disease treatment, according to a large Norwegian clinical trial. Patients with early-stage Parkinson's who took nicotinamide riboside, a form of vitamin B3 that boosts cellular NAD levels, saw no improvement over a year — and actually scored modestly worse on standard disease-severity measures than patients who took a placebo. The trial, led by Dr. Charalampos Tzoulis of Haukeland University Hospital and the University of Bergen, was published this week in JAMA.
The phase 3, randomized, double-blind, placebo-controlled study enrolled 410 people across 11 Norwegian centers, newly diagnosed with Parkinson's within two years and not yet far advanced, randomized to 500 milligrams of nicotinamide riboside twice daily or a matching placebo for 52 weeks. On the primary measure of disease severity (the MDS-UPDRS scale, where higher scores mean worse symptoms), the supplement group worsened by an average of 2.45 points while the placebo group stayed essentially flat — an adjusted difference of 2.72 points favoring placebo (95% CI, 0.47–4.98; P=.02). A key secondary measure of non-motor symptoms also moved the wrong way for the supplement group. Brain scans of dopamine neuron loss showed no difference between arms, and serious adverse events were actually less frequent with the supplement (8.3%) than placebo (14.1%).
A reversal from smaller, earlier trials
The result marks a sharp turn from smaller studies by the same Bergen group that had fueled interest in nicotinamide riboside as a Parkinson's therapy. A 30-patient trial published in Cell Metabolism in 2022 found the supplement raised brain NAD levels and was linked to mild symptom improvement in patients whose levels rose the most; a 2023 follow-up safety study of high doses in 20 patients reported it was well tolerated. Both earlier studies were considerably smaller and used supplement supplied through the manufacturer's research program — a detail that, combined with their size, makes them weaker evidence than this new, independently powered trial.
"NR clearly increased NAD metabolism, but this did not translate into clinical improvement. Our results do not support nicotinamide riboside as a disease-modifying treatment for Parkinson's disease."
Dr. Charalampos Tzoulis, University of Bergen and Haukeland University Hospital, study director
Nicotinamide riboside is sold over the counter as an anti-aging and energy-boosting supplement, often marketed on the strength of NAD's role in cellular metabolism rather than rigorous clinical evidence for any specific disease. This trial is a reminder of how far early biochemical promise can diverge from real-world benefit once tested properly: the supplement did exactly what it was supposed to do at the molecular level — raising NAD metabolism — yet patients taking it did not fare better, and on two measures fared slightly worse, than those on placebo.
The findings are specific to early-stage Parkinson's disease at this dose and duration; they say nothing directly about whether nicotinamide riboside helps or harms in other conditions, and the researchers caution the data don't yet explain why symptom and non-motor scores moved against the supplement. Tzoulis's team says it is still analyzing the data for mechanistic clues and for signs that some patient subgroups responded differently, and the researchers are explicit that they do not recommend nicotinamide riboside or other NAD-boosting supplements for Parkinson's patients outside of controlled research settings.
