Niagen, a patented form of nicotinamide riboside (NR) by ChromaDex, was evaluated for potential benefits in a phase one clinical study involving 20 Parkinson’s disease patients. The study was published in Nature Communications.
 
Treatment with NR at a high dose was safe, well-tolerated, and led to both improvements in NAD metabolome and symptoms of Parkinson’s disease, as measured by a standard evaluation.
 
The study was conducted by a team of researchers at the Haukeland University Hospital and University of Bergen in Norway, led by Caralampos Tzoulis, PhD, MD, professor of neurology and neurogenetics, director of the K.G. Jebsen Center for Translational Research in Parkinson’s Disease, and co-director of the Neuro-SysMed Research Center.
 
Currently, 500,000 Americans are diagnosed with Parkinson’s, making it the second most common neurodegenerative disorder in the U.S.
 
Current treatment options are limited, and there is still a need for novel approaches to manage the effects of the disorder. While current treatments provide partial, temporary relief from motor symptoms, no treatments can yet impact the rate of neurodegeneration or disease progression.
 
The authors theorized that increasing cellular NAD could be a potential strategy to prevent neurodegeneration, as the coenzyme is required for cellular energy metabolism, and requires constant replenishment. NAD replenishment may also target processes involved in neurodegenerative disorders such as mitochondrial function, energy metabolism, DNA repair, epigenetic regulation, inflammation, and more, the authors noted.
 
Study Details
 
In the study, the patients were randomized to receive either a twice-daily dose of 1500 mg of NR or a matching placebo, with the primary outcome being safety and secondary outcomes including mild adverse events, changes in blood and urine NAD metabolome, and change in the clinical severity of Parkinson’s disease.
 
Over the treatment period, which lasted four weeks, NR therapy was well-tolerated with no moderate or severe adverse events, and no significant differences in mild events, which was notable as this was the largest known dose of NR evaluated for safety, the researchers said.
 
NR treatment was associated with a clinical improvement of total symptoms in a test called the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The treatment also augmented the blood NAD metabolome, with up to a five-fold increase in blood NAD+ levels.
 
The authors concluded that the present findings supported extending the dose range of NR in phase 2 clinical studies to 3,000 mg per day with appropriate safety monitoring.
 
Looking Ahead to Phase 2 Research
 
The present findings on NR as a possible candidate treatment for Parkinson’s disease and other neurodegenerative disorders are consistent with prior studies supported through Chromadex’s External Research Program (CERP).
 
In a phase 1 study called NADPARK, for instance, a month-long treatment with 1,000 mg of NR daily was associated with significant increases in cerebral NAD levels and all related metabolites in cerebrospinal fluid. This correlated with improved markers of cerebral metabolism, and a decrease of inflammatory cytokines both in serum and the cerebrospinal fluid of participants.
 
Several other studies also demonstrated the safety and tolerability of NR supplementation at 2,000 mg daily, but this study was the first to demonstrate safety and tolerability at a 3,000 mg daily dose.
 
“As the world’s leading company in NAD+ research and commercialization, ChromaDex is proud to announce this groundbreaking NR-SAFE study from Dr. Tzoulis and his team of researchers that reveals the potential of Niagen NR as a therapy for Parkinson’s disease,” said Rob Fried, CEO of ChromaDex. “This research not only demonstrates the safety and tolerability of high-dose Niagen NR but also highlights its ability to significantly increase NAD+ levels and potentially improve the clinical severity of PD.”
 
“Results of this study build on previous research conducted by our lab, demonstrating that oral NR therapy increases NAD+ levels in the brain of individuals with PD and this is associated with ameliorated brain metabolism and mild clinical improvement,” Tzoulis said.
 
“Abnormal energy metabolism due to dysfunction in the mitochondria has been linked to PD and is believed to play a role in the initiation and progression of the disease. Our previous findings have nominated NR as a potential disease-modifying therapy for PD, which will not only target and rectify disease-specific processes, but may also optimize neuronal metabolism and fortify neurons, rendering them more resilient against age-related stress and neurodegeneration,” he continued. “However, to harness the full therapeutic potential of NR, we need to explore higher dose regimens.”
 
Tzoulis noted that a phase 2/phase 3 study on long-term supplementation with NR is already being conducted in 400 people with Parkinson’s, which is estimated to conclude by the end of 2024 after a year-long intervention. The study, and all others conducted by Tzoulis, is academically-driven and largely based on public funding.