NOPARK: nicotinamide riboside Phase 3

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Charalampos Tzoulis and the Neuro-SysMed group at Haukeland University Hospital and the University of Bergen, Norway, with 11 Norwegian centres. First author Brage Brakedal, senior author Tzoulis. Published in JAMA, 8 October 2026.

What happened

NAD is a molecule every cell uses to make energy. Brain NAD seems to run low in Parkinson's, which fits the energy-failure findings that began with landmark 11. Nicotinamide riboside (NR) is a vitamin B3 form that raises NAD. The earlier Phase 1 study, NADPARK (30 newly diagnosed people, 1,000 mg a day for 30 days, Cell Metabolism 2022), showed that NR was safe and raised brain NAD in a variable way, with mild clinical improvement in those whose NAD rose. NOPARK was the larger test.

• Design. Phase 3, double-blind, placebo-controlled. 410 people aged 35 or older, diagnosed within 2 years, Hoehn and Yahr stage below 3, with a dopamine-transporter scan showing nerve loss. 206 got NR 500 mg twice daily and 204 got placebo, for 52 weeks. Randomised 6 May 2020 to 20 June 2024 (537 screened). 393 were in the main analysis. Final follow-up was 19 June 2025. All took stable dopaminergic treatment, if any, before enrolling.
• Main result. Total MDS-UPDRS (parts I–III) rose 2.45 points on NR and fell 0.27 on placebo: a difference of 2.72 points favouring placebo (95% CI 0.47–4.98, p=0.02). That is below the usual threshold for a clinically important change (5.2 points for worsening).
• Secondary. Four of five key secondary measures, including dopamine-transporter imaging, showed no difference. Non-motor symptoms worsened more on NR (4.22 points, p=0.009).
• Safety. Serious adverse events 8.3% on NR versus 14.1% on placebo.
• Authors' conclusion. NR did not improve clinical outcomes and was linked to worse outcomes than placebo. The findings do not support it as a disease-modifying treatment.

Why it moved us toward a cure

The Phase 1 NADPARK trial had shown that nicotinamide riboside raises brain NAD (landmark 209). It is the largest test of the "refuel the cell" idea so far. The trial did not slow the disease, joining CoQ10 (landmark 26) and creatine (landmark 70) as energy supplements that failed. It argues against general NAD boosters and for treatments that repair mitochondria rather than just feed them.

Outcome

Dead end for NAD-boosting supplements in early Parkinson's. A separate Phase 2 dose study from the same group (N-DOSE, NCT05589766, 81 people, main measure brain NAD) shows as completed in April 2025 with no results posted.

Sources

• Brakedal et al., JAMA 2026, DOI 10.1001/jama.2026.18828 (abstract via Europe PMC, PMID 42848371)
• ClinicalTrials.gov NCT03568968 · Haukeland NOPARK page
• News-Medical summary, 8 Oct 2026
• NADPARK, Cell Metab 2022, DOI 10.1016/j.cmet.2022.02.001
• Not yet verified: the full JAMA text (only the abstract was read, and it is the source for all numbers above); whether NR raised blood or brain NAD in this trial (reported in the news summary, not in the abstract); the N-DOSE result.