Nicotinamide riboside, a derivative of vitamin B3 that enhances cellular concentrations of nicotinamide adenine dinucleotide (NAD+), demonstrated no significant clinical benefit in patients with early Parkinson’s disease, as indicated by the NOPARK randomized trial.
Trial Overview
Marketed as an over-the-counter longevity supplement, nicotinamide riboside intake was linked to modestly worse outcomes when compared to a placebo over the course of one year. This finding was reported by Charalampos Tzoulis, PhD, from Haukeland University Hospital and the University of Bergen in Norway, along with co-authors in a publication in JAMA.
The primary measure of the trial was the change from baseline in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) total scores, accounting for both motor functions and daily living experiences of patients.
After a period of 52 weeks, the MDS-UPDRS total scores in the nicotinamide riboside group worsened by an average of 2.45 points, while scores in the placebo group displayed a trend towards improvement, with an adjusted mean difference of 2.72 points (95% CI 0.47-4.98, P=0.02).
Furthermore, the burden of nonmotor symptoms also increased more significantly in patients receiving nicotinamide riboside (P=0.009). No imaging evidence was found to suggest that nicotinamide riboside slowed or accelerated changes within the dopamine system.
Adverse Events Observed
Serious adverse events were noted in 8.3% of participants in the nicotinamide riboside group compared to 14.1% in the placebo cohort. The most frequently reported adverse event in both groups was hypertension; however, most were deemed unrelated to the treatment. Tragically, one participant in the nicotinamide riboside group experienced cardiac arrest, resulting in death.
As Tzoulis remarked, the findings do not support the use of nicotinamide riboside as a treatment to slow the progression of Parkinson’s disease.
Biological Rationale and Previous Studies
“We had a solid biological rationale for testing this treatment, as earlier, smaller clinical studies had shown promising results,” Tzoulis stated. “Nicotinamide riboside was confirmed to enhance NAD metabolism, yet this did not translate into clinical improvement.”
NAD is crucial for cellular energy metabolism, DNA repair, and regulation of inflammation, with NAD+ being the active form utilized by the body for energy production and repair. Both animal studies and small human trials have hinted that nicotinamide riboside, a precursor to NAD+, may provide benefits in the context of Parkinson’s disease.
Details of the NOPARK Trial
The phase III NOPARK trial aimed to determine whether nicotinamide riboside could delay the progression of Parkinson’s disease. This trial is the largest to date examining an NAD-boosting treatment for neurological disorders. A total of 410 patients were randomized across 11 centers in Norway. Participants, diagnosed with Parkinson’s within two years prior to enrolment, had a Hoehn and Yahr disease stage of less than 3, confirmatory findings on dopamine transporter single-photon emission computed tomography, and stable dopaminergic treatment. Individuals with dementia, atypical parkinsonism, other neurodegenerative conditions, or recent high-dose vitamin B3 consumption were excluded.
The study cohort had a mean age of 66 years, with 66% being male. Patients were assigned to receive either 500 mg of oral nicotinamide riboside twice daily (206 individuals) or a placebo (204 individuals) for a duration of one year.
Median adherence to nicotinamide riboside was remarkably high at 99.6%. This treatment led to substantial increases in NAD+ ratios and total blood NAD levels: by week 52, a mean between-group difference in total blood NAD of 30.00 μM was observed (P<0.001).
No significant difference was detected between groups in terms of changes in Montreal Cognitive Assessment scores. The EuroQol 5-Dimension 5-Level assessment (EQ-5D-5L) index values were comparatively lower in the nicotinamide riboside group than in the placebo cohort.
Conclusion and Future Research
“Although the overall difference in total MDS-UPDRS scores was modest and fell below established thresholds for clinical significance, the consistency of these findings across clinical endpoints and sensitivity analyses underlines the robustness of the results,” Tzoulis and colleagues noted.
Given the extensive use of nicotinamide riboside as an over-the-counter supplement, coupled with the rising number of trials investigating NAD augmentation, these findings possess immediate clinical implications.
The lack of progression in the placebo group during the trial may partially reflect the effects of dopaminergic therapy. The researchers suggested, “Sustained NAD augmentation may induce unfavorable biological effects in relation to Parkinson’s disease through unrecognized mechanisms, or nicotinamide riboside might interact negatively with dopaminergic treatment, leading to symptomatic deterioration.”
The trial did not include a washout phase, and the researchers acknowledged that dopamine transporter imaging has limited sensitivity in detecting subtle changes over a one-year period.
Nicotinamide riboside is still under investigation in clinical settings. The supplement manufacturer Niagen Bioscience has recently announced intentions to initiate a large randomized placebo-controlled trial in collaboration with Mass General Brigham, targeting healthy aging outcomes and related biomarkers.
Nota de descargo de responsabilidad: La información proporcionada en este documento es solo para fines informativos y educativos. No sustituye el consejo médico profesional ni el tratamiento por parte de un médico calificado. Siempre consulte a un profesional de la salud para preguntas sobre condiciones médicas o tratamientos.
Fuente: https://www.medpagetoday.com/neurology/parkinsonsdisease/123349
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