Encouraging early research results prompted scientists to study whether NAD supplementation could improve Parkinson’s disease symptoms, and they conducted a year-long clinical trial involving 410 patients.
Study: Treatment of patients with early-stage Parkinson’s disease with the nucleoside nicotinamide. Image courtesy of Fabian Montano Hernandez / Shutterstock
A recent randomized controlled trial (RCT) published in the Journal of the American Medical Association (JAMA) found that oral treatment with the NAD precursor nicotinamide nucleoside did not improve the prognosis of patients with early-stage Parkinson’s disease (PD), and their clinical outcomes were slightly worse compared to placebo.
Parkinson’s disease is one of the leading causes of neurological disorders. Current treatments can only alleviate symptoms and are unable to reverse the disease’s progression.
In the human body, nicotinamide nucleoside is metabolized into nicotinamide adenine dinucleotide (NAD). Preclinical studies show that increased NAD levels can impact mitochondrial function and homeostasis, DNA damage repair, protein homeostasis, and oxidative inflammation pathways. Animal studies have also shown that NAD has a neuroprotective effect, manifested by enhanced protection of dopaminergic neurons, improved motor function, and increased survival.
Initial results from short-term clinical trials showed increased NAD levels in the brain, reduced inflammatory markers in the cerebrospinal fluid, and increased expression of genes associated with mitochondrial and protein homeostasis pathways. Preliminary analysis also showed improvement in disease markers.
It remains unclear whether long-term use of the nucleoside nicotinamide can alter the course of early-stage Parkinson’s disease and improve clinical efficacy. The aim of the NOPARK study is to test this hypothesis.
This study involved 410 patients with early-stage Parkinson’s disease who participated in a randomized, double-blind, placebo-controlled phase III clinical trial conducted at 11 centers in Norway. Of these, 393 patients were included in the main analysis population, and data from 391 patients were used to construct the primary outcome model.
All participants were 35 years of age or older and had been diagnosed with Parkinson’s disease within two years prior to participating in the study.
Inclusion criteria for the study included early-stage disease (below stage 3) according to the Hoehn and Yahr staging system, brain scans for the presence of dopamine transporters confirming denervation of the dopaminergic pathway in the substantia nigra and striatum, and stable dopaminergic treatment at the time of study inclusion.
Participants were randomly assigned to one of two groups: one received oral nicotinamide nucleoside (500 mg twice daily) or a placebo for 52 weeks. The primary efficacy endpoint was the change in the total score (parts one through three) of the Movement Disorder Association Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The scale ranges from 0 to 236, with higher scores indicating more severe disease.
The study also examined five key secondary outcomes: MDS-UPDRS parts one through three, brain dopamine transporter imaging, and the Non-Motor Symptom Scale (NMSS) score, with higher scores indicating more symptoms.
The average age of the participants was 65.6 years, and 34% were women. The study was funded by the Norwegian Research Institute, and the experimental drug was provided by ChromaDex, a subsidiary of Niagen Bioscience. Some researchers disclosed patents related to the treatment of Parkinson’s disease with nicotinamide nucleosides, which were licensed by Niagen Bioscience.
Both groups of patients showed modest improvement during the first 13 weeks, with a more significant improvement in the placebo group. Subsequently, scores in the nicotinamide nucleoside group continued to increase, while scores in the placebo group initially declined until week 26 and then began to increase again.
At week 52, the mean total score calculated by the model increased by 2.45 points in the nicotinamide nucleoside group, while it decreased by 0.27 points in the placebo group. The adjusted mean difference was 2.72 points, with the placebo group performing better than the nicotinamide nucleoside group, and this difference was statistically significant.
Medication adjustments prior to study entry may also partly explain the early improvement in the placebo group, but the analysis taking into account dopaminergic therapy is consistent with the main results.
Of the five secondary efficacy outcomes, only one showed a significant difference between groups. The NMSS score (which assesses symptoms such as mood changes, sleep problems, and digestive disorders) was slightly higher in the nicotinamide nucleoside group and lower in the placebo group, with an adjusted difference of 4.22 points between the two groups.
A sensitivity analysis confirmed these results. The exploratory measure of health-related quality of life also showed that the placebo group performed better, but this analysis did not adjust for multiple comparisons.
Serious adverse events were observed in 8.3% of participants treated with nicotinamide nucleoside, compared with 14.1% of those receiving placebo. The difference between the two groups was not statistically significant, and the overall incidence of adverse events was similar in both groups.
Preliminary analysis revealed that total serum NAD levels were significantly elevated in the nicotinamide nucleoside group, with a mean difference of 30 μM between groups. The NAD+/NADH ratio, as well as most measured NAD metabolic intermediates and breakdown products, were also significantly elevated. Among subjects undergoing brain spectroscopic analysis, there were no statistically significant differences in changes in the NAD/ATP (a molecule involved in cellular energy production) ratio in the brain between groups after 52 weeks.
The findings differ from those of earlier short-term clinical trials. The authors suggest that persistently elevated NAD+ levels may have adverse effects on biological processes in patients with Parkinson’s disease, although the specific mechanisms remain unclear.
Another possibility is that nicotinamide nucleoside may interact with dopaminergic therapy for Parkinson’s disease, leading to an exacerbation of symptoms. Dopamine transporter binding was reduced in both groups, but the difference between the groups was not statistically significant. The authors note that this finding is consistent with the drug-drug interaction hypothesis, as well as with preclinical data suggesting that nicotinamide nucleoside may affect dopamine metabolism.
Compared to the placebo group, subjects experienced a higher number of non-motor symptoms, suggesting that dopaminergic mechanisms alone may not be the primary cause, although the specific etiology remains unclear. Researchers have not yet identified the reasons for these differences.
This study has some limitations. In patients receiving medication, subtle changes in motor symptoms may go undetected, reducing the ability to detect subtle differences in treatment. Furthermore, the lack of a drug withdrawal period limits the ability to distinguish between changes in symptoms and changes in disease progression.
The neuroimaging technology used was not sensitive enough to detect subtle changes over the course of a year, so the results cannot rule out subtle changes in dopaminergic neurodegeneration.
The results showed that in this group of Parkinson’s disease patients, after 52 weeks of treatment with nicotinamide nucleoside, the prognosis was slightly worse compared to placebo, and no clinical benefit was observed. This statistically significant difference was below the clinically significant threshold for disease progression.
”These results do not support the use of nicotinamide nucleoside as a disease-modifying therapy for Parkinson’s disease.” The authors also concluded that, at the doses and durations tested, the results do not support its use as a symptomatic treatment for Parkinson’s disease. Because this compound is available over-the-counter and is widely used as a dietary supplement, these results have clinical significance as research into NAD supplementation continues.
Dr. Ridge Thomas is an obstetrician and gynecologist who graduated from the Government School of Medicine at the University of Calicut in Kerala in 2001. After graduating, Ridge worked for several years as a full-time consultant physician at a private hospital. She consulted with hundreds of patients facing pregnancy and infertility issues and delivered over 2,000 babies, always striving for natural childbirth rather than surgical intervention.
Thomas, Lidgie. (October 12, 2026). Year-long trial finds NAD supplements fail to improve early Parkinson’s disease symptoms. News-Medical. Retrieved October 16, 2026, from https://www.news-medical.net/news/20261012/Year-long-trial-finds-NAD-boosting-supplement-fails-to-improve-early-Parkinsons-symptoms.aspx.
Thomas, Liji. “A Year-Long Study Finds NAD Supplements Did Not Improve Early Symptoms of Parkinson’s Disease.” Medical News. October 16, 2026.
Thomas, Liji. “Year-long trial finds NAD supplements fail to improve early Parkinson’s disease symptoms.” News-Medical. https://www.news-medical.net/news/20261012/Year-long-trial-finds-NAD-boosting-supplement-fails-to-improve-early-Parkinsons-symptoms.aspx. (Accessed October 16, 2026).
Thomas, Liji. 2026. Year-long trial finds NAD supplements fail to improve early Parkinson’s disease symptoms. News-Medical, accessed October 16, 2026, https://www.news-medical.net/news/20261012/Year-long-trial-finds-NAD-boosting-supplement-fails-to-improve-early-Parkinsons-symptoms.aspx.
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Post time: Oct-16-2026