NOPARK: The 52-Week NR Trial in Early Parkinson's That Favored Placebo

NOPARK randomized 410 people with early Parkinson's disease to nicotinamide riboside (NR) or placebo for 52 weeks. NR did not improve the main rating score. The NR group got worse than placebo by an adjusted 2.72 points on that score, and nonmotor symptoms also worsened more on NR. This is a Mt. Angel Vitamins company white paper, not a journal article, and it has not been through journal peer review. It reads the trial's published abstract alongside the earlier NR studies in Parkinson's and the human NAD+ trials, and it says where the evidence stops.

If you're not a researcher

• The question: Does nicotinamide riboside (NR) slow Parkinson's disease in people recently diagnosed? In NOPARK, no. After 52 weeks the NR group's rating score had risen 2.72 points more than placebo's (adjusted).
• The surprise: The placebo group's average barely moved over the year, down 0.27 points. The NR group's average rose 2.45 points.
• The evidence: One large, double-blind, placebo-controlled trial with 393 people analyzed. The earlier NR trials in Parkinson's had 20 and 30 people and were built to test safety and brain NAD+.
• The dose: NOPARK gave 500 mg twice a day, or 1,000 mg a day. The highest dose in the Parkinson's trials we checked is 3,000 mg a day, for four weeks, in NR-SAFE, where 10 of 20 people took it.
• The limits: Early disease only, one dose, one country. The nonmotor finding came from one of five key secondary outcomes, so a second trial has to confirm it.
• The one thing to do: If you already take NR, keep any prescribed treatment in place and ask your clinician before you change anything. Check the milligrams on any label against the trial doses.
• Full plain-English guide: the NR monograph.

What did the NOPARK trial test?

NOPARK randomized 410 people with early Parkinson's disease to NR or a matching placebo. The NR group took 500 mg twice a day for 52 weeks (206 people), and 204 people took placebo. The trial ran at 11 centers in Norway, enrolled people from May 6, 2020 to June 20, 2024, and completed follow-up on June 19, 2025. It is registered as NCT03568968. Participants were 35 or older, diagnosed within the previous two years, at Hoehn and Yahr stage below 3 (a standard staging scale), and on stable Parkinson's medication. The analyzed group averaged 65.6 years old, and 34% were women.

The primary outcome was the change from baseline to week 52 in the MDS-UPDRS parts I to III total, a 0 to 236 score where higher means worse. Five key secondary outcomes followed: the three parts separately, a dopamine transporter SPECT brain scan, and the Non-Motor Symptoms Scale (NMSS), which runs from 0 to 360.

Why was NR tested in Parkinson's?

NR is one of several NAD+ precursors. NAD+ is a coenzyme that more than 400 enzymes need. The NIH Office of Dietary Supplements lists NR among the "related derivatives" of niacin, alongside nicotinic acid and nicotinamide (NIH ODS). The NOPARK authors describe NR as proposed for Parkinson's on the basis of "preclinical and early studies."

The mouse evidence was mixed. A 2026 preprint from the National Institute of Environmental Health Sciences and the National Institute on Aging gave NR in drinking water to mice with a double-hit Parkinson's model (Saha et al., preprint). Motor performance improved and dopamine release rose, but NR did not prevent loss of dopamine neurons. A disease-modifying claim needs the disease process to slow, so better movement without protected neurons answers a different question. The preprint has not been peer reviewed.

What did the earlier trials find?

NADPARK randomized 30 newly diagnosed people to NR (1,000 mg a day) or placebo for 30 days. NR was well tolerated and raised brain NAD+ in a significant but variable way. People whose brain NAD+ rose showed changes in brain metabolism and a mild clinical improvement (Brakedal et al., 2022).

NR-SAFE gave 20 people with Parkinson's NR 1,500 mg twice a day or placebo for four weeks. The primary outcome was safety. No moderate or severe adverse events occurred, and blood NAD+ levels rose up to fivefold. The rating score improved in the NR group, but that change was also associated with a shorter time since the last levodopa dose. The authors proposed testing 3,000 mg a day in phase II trials with safety monitoring (Berven et al., 2023).

A four-ingredient mix tested in a 2025 phase II trial included 1 g of NR per dose, along with L-serine, N-acetyl-L-cysteine and L-carnitine tartrate. Of 48 people with mild to moderate Parkinson's, 32 got the mix and 16 got placebo, for 84 days. Motor scores did not improve. The Montreal Cognitive Assessment (MoCA) rose significantly within the mix group, but the full text reports no significant difference between groups at any time point. NR was one of four ingredients, so the trial cannot isolate it (Yulug et al., 2025).

What did NOPARK find?

At week 52 the NR group's MDS-UPDRS score rose 2.45 points (95% CI 0.80 to 4.10). The placebo group's score fell 0.27 points (95% CI negative 1.95 to 1.40). The adjusted difference was 2.72 points in favor of placebo (95% CI 0.47 to 4.98; P = .02).

Four of the five key secondary outcomes showed no significant difference. The NMSS did: nonmotor burden rose more on NR, with an adjusted difference of 4.22 points (95% CI 1.07 to 7.37; P = .009). Serious adverse events occurred in 17 of 205 people on NR (8.3%) and 29 of 205 on placebo (14.1%) in the safety population. The abstract reports these counts without a statistical test.

Evidence grades by outcome:

What does the NOPARK result show, and what does it not?

The direction is clear, and the size is modest. The adjusted gap of 2.72 points is about half of the 5.2-point change the trial itself calls clinically important for worsening.

The trial answers a narrow question: one dose, one year, early disease, one country. It says nothing about higher doses or later stages.

The nonmotor finding is one significant result among five key secondary outcomes. It is a reason for a second trial, not proof of harm.

The abstract gives no mechanism and does not say whether NAD+ rose in these participants. Seventeen randomized people were outside the primary analysis, and the abstract does not say why. This section draws on the abstract and key points. The authors' full discussion and limitations section is worth reading before you rely on any point here.

Established, proposed, and what would settle it

Established. NR raises NAD+ in human blood and tissue. In one large trial, 1,000 mg a day for 52 weeks did not improve the rating score in early Parkinson's, and the NR group scored worse than placebo.

Proposed. NR and NMN may raise circulating NAD+ partly through gut bacteria that convert them to nicotinic acid. Christen et al. propose this model from fermentation and whole-blood experiments (Christen et al., 2026). Higher doses may work better, but that is untested in a long trial.

What would settle it. A trial above 1,000 mg a day with the same primary outcome would test the dose question. A second trial that prespecifies the nonmotor measure would test the NMSS signal. Reporting NAD+ alongside clinical scores in a large trial would show whether the blood rise tracks any clinical change.

What do the other human trials show?

Outside Parkinson's, NR has mostly been tested for NAD+ levels. The table of NAD+ precursor trials that missed sets these alongside the Parkinson's data.

Elhassan et al. gave 12 aged men 1 g of NR a day for 21 days in a randomized, double-blind, placebo-controlled crossover trial. Muscle NAD+ metabolites rose. Mitochondrial bioenergetics did not change, and circulating inflammatory cytokines fell (Elhassan et al., 2019).

Vreones et al. gave 22 healthy older adults 500 mg of NR twice a day for six weeks in a placebo-controlled crossover trial. NR raised NAD+ in neuron-enriched plasma vesicles, which showed lower Aβ42, pJNK and pERK1/2. These are biomarkers, not clinical outcomes (Vreones et al., 2022).

Christen et al. randomized 65 healthy adults in an open-label, placebo-controlled study. After 14 days NR and NMN raised circulating NAD+, while nicotinamide's effect was brief. Several authors are affiliated with Nestlé Research and Nestlé Health Science. For a head-to-head look at NMN and NR, see NMN vs NR.

Glossary

• NAD+: a coenzyme that more than 400 enzymes need (NIH ODS).
• Nicotinamide riboside (NR): a niacin-family compound the body uses to make NAD+.
• NMN: nicotinamide mononucleotide, a closely related NAD+ precursor.
• Nicotinamide: another niacin form, also called niacinamide.
• Nicotinic acid: the niacin form that causes skin flushing at high doses.
• MDS-UPDRS: the Movement Disorder Society Unified Parkinson's Disease Rating Scale; parts I to III total 0 to 236.
• NMSS: the Non-Motor Symptoms Scale, 0 to 360, where higher means more nonmotor burden.
• Hoehn and Yahr stage: a standard staging scale for Parkinson's severity.
• DaT SPECT: a dopamine transporter brain scan.
• Levodopa: the main medicine that replaces dopamine in Parkinson's.
• 95% CI: the range of gaps consistent with the data.
• Adjusted difference: the gap between groups after statistical adjustment.
• Preprint: a report posted before journal peer review.
• Double-blind, placebo-controlled: neither participants nor staff know who got the active treatment, and the comparison is a dummy treatment.

References

1. Brakedal B, et al. Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial. JAMA. 2026. PubMed 42848371. DOI 10.1001/jama.2026.18828.
2. Berven H, et al. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nature Communications. 2023;14(1):7793. PubMed 38016950. DOI 10.1038/s41467-023-43514-6.
3. Brakedal B, et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metabolism. 2022;34(3):396-407. PubMed 35235774. DOI 10.1016/j.cmet.2022.02.001.
4. Elhassan YS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports. 2019;28(7):1717-1728. PubMed 31412242. DOI 10.1016/j.celrep.2019.07.043.
5. Vreones M, et al. Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging Cell. 2022. PubMed 36515353. DOI 10.1111/acel.13754.
6. Christen S, et al. The differential impact of three different NAD boosters on circulatory NAD and microbial metabolism in humans. Nature Metabolism. 2026;8(1):62-73. PubMed 41540253. DOI 10.1038/s42255-025-01421-8.
7. Yulug B, et al. Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial. Brain Communications. 2025;7(1):fcae478. PubMed 39816194. DOI 10.1093/braincomms/fcae478.
8. Saha S, et al. Nicotinamide Riboside Enhances Mitochondrial Bioenergetics and Dopaminergic Signaling Independent of Neuron Survival in a Double-Hit Parkinson's Model. Research Square. 2026. Preprint. PubMed 42370283. DOI 10.21203/rs.3.rs-9970859/v1.
9. NIH Office of Dietary Supplements. Niacin: Health Professional Fact Sheet. https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/

Next reads

• The full NR monograph: the dose table, safety notes and trial list for the ingredient.
• The 2026 NMN and NR buyer's guide: nine products compared on six criteria, including dose against the human trials.
• The NAD+ and cellular energy guide: the pillar that covers the whole NAD+ cluster.

More on NAD+ and Cellular Energy: The Complete Guide