The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease

• Published in: Cell metabolism 2022-03, Vol.34 (3), p.396-407.e6
• Main Authors: Brakedal, Brage, Dölle, Christian, Riemer, Frank, Ma, Yilong, Nido, Gonzalo S., Skeie, Geir Olve, Craven, Alexander R., Schwarzlmüller, Thomas, Brekke, Njål, Diab, Joseph, Sverkeli, Lars, Skjeie, Vivian, Varhaug, Kristin, Tysnes, Ole-Bjørn, Peng, Shichun, Haugarvoll, Kristoffer, Ziegler, Mathias, Grüner, Renate, Eidelberg, David, Tzoulis, Charalampos
• Format: Article
• Language: English
• Subjects: Dietary Supplements; disease modifying; experimental therapy; Humans; mitochondria; NAD; NAD - metabolism; neurodegeneration; neuroprotective; Niacinamide - analogs & derivatives; Niacinamide - pharmacology; Niacinamide - therapeutic use; nicotinamide adenine dinucleotide; Parkinson Disease - drug therapy; parkinsonism; Pyridinium Compounds - therapeutic use; treatment
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2022.02.001

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson’s disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels—measured by 31phosphorous magnetic resonance spectroscopy—and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials. [Display omitted] •Oral NR increases brain NAD levels in individuals with Parkinson’s disease•NR intake alters cerebral metabolism in Parkinson’s disease•Cerebral NAD increase is associated with clinical improvement in Parkinson’s disease•NR induces transcription of mitochondrial, lysosomal, and proteasomal pathways Researchers from Haukeland University Hospital conducted a phase I trial of NAD-replenishment therapy with oral nicotinamide riboside (NR) in Parkinson’s disease (PD). NR increased cerebral NAD levels, and this was associated with altered brain metabolism and clinical improvement. The findings nominate NR as a potential neuroprotective treatment for PD.