NAD booster misses the mark in early Parkinson's disease

Clinical takeaway: Do not recommend nicotinamide riboside as a disease-modifying therapy for early Parkinson disease based on current evidence.

Nicotinamide riboside, an over-the-counter supplement, boosts nicotinamide adenine dinucleotide (NAD), a molecule involved in cellular energy metabolism and repair. Promising animal studies and short-term human trials raised hopes for a treatment that could alter Parkinson disease progression rather than simply relieve symptoms.

In the NOPARK phase 3 trial, investigators randomized 410 adults with Parkinson disease diagnosed within the previous 2 years to nicotinamide riboside 500 mg twice daily or placebo for 52 weeks. The primary analysis included 393 participants, whose mean age was 66 years. By study end, overall Parkinson symptoms, measured with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), worsened by about 2.5 points in the nicotinamide riboside group while remaining essentially unchanged in the placebo group, producing a statistically significant difference favoring placebo.

The disappointing result extended beyond the primary endpoint. Nonmotor symptom burden increased with nicotinamide riboside but improved with placebo, yielding a roughly 4-point disadvantage for active treatment. Researchers found no evidence that nicotinamide riboside preserved dopamine transporter imaging measures, slowed motor decline, or improved cognition. Quality-of-life scores were also slightly worse among patients receiving the supplement.

Notably, the therapy clearly engaged its intended biological target. Blood NAD levels rose substantially in treated patients, confirming systemic activity. Yet those biochemical changes did not translate into clinical benefit. Overall adverse event rates were similar between groups, and serious adverse events were numerically less common with nicotinamide riboside, suggesting the negative findings reflected lack of efficacy rather than excess toxicity.

“These findings do not support nicotinamide riboside as a disease-modifying or symptomatic treatment for Parkinson disease,” the authors concluded.

Source: Brakedal B, et al. (2026 Oct 8) JAMA. Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial