Home > Articles > Nicotinamide riboside in Parkinson's: what the NOPARK trial recorded
Nicotinamide riboside in Parkinson's: what the NOPARK trial recorded
Prepared by: Research Desk
Prepared by: Research Desk. Sources are linked for verification.
Nicotinamide riboside (NR) is one of the most studied NAD+ precursors in people. NOPARK is a Norwegian phase 3 trial that tests NR in early Parkinson's disease against placebo over one year, with a clinical rating scale as its primary outcome [1]. This explainer sets out what the trial was registered to measure, how it grew out of the smaller NADPARK study, and why a change in an NAD+ biomarker is a different thing from a change in a clinical outcome.
The short version
NOPARK is registered as NCT03568968. The registry record describes a randomized, double-blind, placebo-controlled phase 3 trial of NR in people with early Parkinson's disease, followed for 52 weeks. Its primary outcome is change in the MDS-UPDRS rating scale [1].
NADPARK (NCT03816020) was the earlier phase 1 study. It examined whether NR changes NAD+ levels in the brain and how well it is tolerated over about a month [2][3].
NOPARK results are not yet among this site's verified sources, so this page describes the registered design only. Outcome figures will be added once they can be checked against the primary publication.
The core lesson for NAD+ research is that a higher NAD+ reading in blood or brain is a biomarker change. It is not the same thing as a change in how a disease progresses.
Why researchers looked at NR in Parkinson's disease
NAD+ has two jobs in cells. It carries electrons for energy metabolism, and it is consumed as a substrate by enzymes such as PARPs, sirtuins and CD38. Our NAD+ guide walks through both roles. Mitochondrial dysfunction has long been studied in Parkinson's disease. Because NAD+ sits at the centre of mitochondrial energy metabolism, some research groups proposed that raising NAD+ supply might alter disease-relevant biology. The NADPARK investigators framed their study around this rationale [3].
There is also a broader background claim that NAD+ falls with age. Human tissue data support it in places. One study of human skin samples reported age-associated changes in NAD+ metabolism and oxidative stress markers [5]. Our article on whether NAD+ declines with age looks at how consistent those measurements are across tissues. An age-related fall in a molecule does not, by itself, show that restoring it changes a disease. Trials like NOPARK exist to test exactly that gap.
Step one: NADPARK, the phase 1 study
NADPARK was a small, randomized, placebo-controlled phase 1 trial in people with newly diagnosed Parkinson's disease [2][3]. Its main questions were about tolerability and target engagement. In other words, does oral NR reach the brain and change NAD+ metabolism there?
The published report in Cell Metabolism described the following findings [3]:
NR was well tolerated over the roughly 30-day study period.
Brain NAD+ levels rose on average in the NR group, measured with phosphorus magnetic resonance spectroscopy. The increase varied between participants.
NAD-related metabolites increased in cerebrospinal fluid.
Participants whose brain NAD+ rose showed altered cerebral metabolism on FDG-PET imaging. The authors reported this as being associated with a mild change in clinical scores.
Blood and muscle samples showed changes in the NAD+ metabolome and in gene-expression signatures linked to mitochondrial, lysosomal and proteasomal function.
A phase 1 study of this size cannot establish whether an intervention alters the course of a disease. Clinical-score changes in a month-long trial of a few dozen people are exploratory by design. What NADPARK provided was evidence of target engagement, and that is what justified a larger, longer trial.
Step two: NOPARK, the phase 3 trial
The ClinicalTrials.gov record for NOPARK sets out the pre-specified design [1]:
Feature | As registered |
|---|---|
Phase | 3 |
Design | Randomized, double-blind, placebo-controlled |
Population | Adults with early Parkinson's disease |
Planned size | Around 400 participants |
Follow-up | 52 weeks |
Primary outcome | Change in MDS-UPDRS total score |
Setting | Multiple centres in Norway |
The MDS-UPDRS is the Movement Disorder Society's version of the Unified Parkinson's Disease Rating Scale. It combines ratings of non-motor and motor experiences of daily living and a motor examination. Higher scores mean more severe symptoms. A trial testing whether an intervention slows progression typically compares how much the score rises in each group over the follow-up period.
Registration matters here. The record fixes the primary outcome before results are known. This makes it harder to "rescue" an unfavourable trial by highlighting a secondary measure after the fact [1].
Where NOPARK results stand on this site
The primary NOPARK results publication is not yet among the sources this site has verified. For that reason, this page does not report outcome findings, effect sizes, confidence intervals or adverse-event counts. The registry record [1] remains the reference point for the pre-specified design, and this section will be updated once the figures can be checked against the primary publication.
Some general points apply when reading coverage of any phase 3 result in this field:
Start with the primary outcome. The registered primary endpoint, here the MDS-UPDRS change over 52 weeks [1], is the question the trial was powered to answer. Headlines built on secondary measures deserve more caution.
Phase matters. A phase 1 study such as NADPARK is built to show tolerability and target engagement [3]. A phase 3 trial is built to test clinical change, so on clinical questions it carries more weight than an early-phase signal.
Read direction and size together. A between-group difference should be read alongside its uncertainty range and the authors' pre-specified analysis, not as a single number in isolation.
One trial covers one population. A trial in early Parkinson's disease over one year does not answer questions about other conditions, other precursors or other study designs.
Why a rise in NAD+ is not a clinical result
NR studies in healthy adults show the split between biomarker and outcome. In a randomized crossover trial of 30 healthy middle-aged and older adults, six weeks of NR was well tolerated. It raised NAD+ in peripheral blood mononuclear cells [4]. Changes in physiological measures in that study were modest and exploratory.
That distinction runs through precursor research generally. A rise in NAD+ readings in blood or cells is target engagement, while functional or clinical endpoints are separate questions that need their own evidence. A 2026 PRISMA-guided systematic review gathered preclinical and clinical evidence on NAD+ supplementation in one place [6]. Its scope, covering both animal and human studies, makes it a useful map for seeing which findings come from which kind of study. Our summary of nicotinamide riboside research lists what each human NR trial actually measured.
How NAD+ is measured also shapes how studies are read. Whole blood, isolated cells, cerebrospinal fluid and brain spectroscopy each report different quantities in different units. Our guide to reading an NAD+ test report explains why numbers from different methods cannot be compared directly.
Where regulation fits
In the United States, NR is sold as a dietary supplement ingredient. Dietary supplements do not need FDA approval for safety or effectiveness before they are marketed [7]. A supplement listing is therefore not a finding that the ingredient does anything for a disease. Under U.S. rules, a supplement cannot be marketed to diagnose, treat, cure or prevent any disease. Our explainer on NMN, NR and IV NAD+ under U.S. rules covers how these categories work.
A checklist for reading NAD+ trial news
What phase was it? Phase 1 studies look at tolerability and target engagement. Phase 3 trials test clinical outcomes.
What was the primary outcome? Check the registry record and compare it with the headline.
Was the outcome a biomarker or a clinical measure? A rise in NAD+ is a biomarker change.
How many participants, and for how long? Small, short studies are hypothesis-generating.
Is the full paper available? Press summaries often drop the effect sizes and uncertainty ranges.
Tools for comparing NAD+ blood tests
Readers who follow this research often want to understand the assays behind consumer NAD+ results. A consumer test does not diagnose any condition. When comparing test products as measurement tools, these neutral criteria are the most useful:
What is measured: total NAD+, the NAD+/NADH ratio or related metabolites, and whether results are reported for whole blood or a specific cell fraction.
Method: LC-MS/MS or enzymatic cycling assays, with a published method description or validation data.
Sample type: dried blood spot or venous draw, and how sample stability during shipping is handled.
Transparency: clear pricing, stated turnaround times and explicit reference intervals with their source population.
Data privacy: what happens to samples and results, and whether data are shared or sold.
Our NAD+ test buyer's guide compares formats in more detail.
How this site handles affiliate relationships, and what we never publish, is explained on our about page.
Frequently asked questions
What was the NOPARK trial?
NOPARK is a Norwegian phase 3, randomized, double-blind, placebo-controlled trial of nicotinamide riboside in early Parkinson's disease, registered as NCT03568968. It was designed to follow participants for 52 weeks, and its primary outcome is change in the MDS-UPDRS rating scale [1].
What did NOPARK find about Parkinson's outcomes?
The NOPARK results publication is not yet among this site's verified sources, so this page does not report its findings. The registry record confirms the pre-specified primary outcome, change in MDS-UPDRS over 52 weeks [1]. Specific results will be added once they can be checked against the full publication.
How does NOPARK relate to NADPARK?
NADPARK was a smaller phase 1 study. It reported that NR was well tolerated and raised brain NAD+ levels on average, with variation between participants [2][3]. Those target-engagement findings supported running the larger NOPARK trial to test clinical outcomes.
Does a higher NAD+ reading mean a precursor is working?
A higher reading shows that a precursor changed NAD+ metabolism, which is a biomarker effect. In healthy older adults, for example, NR raised NAD+ in blood cells while changes in physiological measures were modest and exploratory [4]. Whether a biomarker change carries through to clinical outcomes has to be tested separately, in trials designed for that question.
Related on this site
Nicotinamide riboside research: what human trials have measured
NAD+ explained: biochemistry, precursors, testing and human evidence
Reading an NAD+ test report: units, sample types and reference ranges
Last updated: 22 October 2026.
Not medical advice. This page reports published research and regulatory records for information only.
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