Nicotinamide riboside, a form of vitamin B3 widely marketed as an over-the-counter longevity supplement, failed to meet its primary endpoint in a phase III trial for early Parkinson's disease. The NOPARK study, published in JAMA, randomized 410 patients across 11 centers in Norway to receive either 500 mg of nicotinamide riboside twice daily or placebo for one year.
After 52 weeks, total MDS-UPDRS scores—which combine motor examination and patient-reported daily living experiences—worsened by an average of 2.45 points in the treatment group, while the placebo group trended toward improvement. The adjusted mean difference was 2.72 points (95% CI 0.47–4.98, P=0.02). Nonmotor symptom burden also worsened more with nicotinamide riboside. Dopamine transporter imaging showed no evidence that the supplement slowed or accelerated dopamine-system changes. Serious adverse events occurred in 8.3% of the treatment group versus 14.1% of the placebo group; one treated participant died after a cardiac arrest.
The researchers noted that the trial had a strong biological rationale and that earlier smaller studies had been encouraging, but the marked increase in NAD metabolism did not translate into clinical improvement. They suggested that sustained NAD augmentation might have unfavorable biological effects in Parkinson's disease or could interact with dopaminergic therapy. Given the supplement's widespread use and the growing number of NAD-augmentation trials, the authors said the findings have immediate clinical relevance.