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Cell Metabolism2022clinicalnr

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

Brakedal B, Dölle C, Riemer F, et al.

Key finding

Oral NR at 1 g/day for 30 days raises cerebral NAD+ in newly diagnosed Parkinson's patients, with transcriptomic and motor-symptom trends favoring treatment.

Summary

Randomized, double-blind, placebo-controlled phase I trial of NR in 30 newly diagnosed, drug-naïve Parkinson's disease patients. Participants received 1 g/day NR or placebo for 30 days. Primary outcome was brain NAD+ measured by 31P-MRS. NR supplementation produced a significant increase in cerebral NAD+ and NAD+-related metabolites, with 10 of 13 NR-treated patients classified as biochemical responders. Responders showed upregulation of mitochondrial and metabolic gene programs in peripheral blood mononuclear cells and skeletal muscle, as well as a trend toward clinical symptom improvement on the MDS-UPDRS motor scale. The trial provided the first human evidence that an oral NAD+ precursor can raise NAD+ in the living human brain, directly addressing skepticism about whether NR crosses the blood-brain barrier or its metabolites reach central tissue. Safety was excellent. NADPARK motivated larger follow-up trials (NR-SAFE, NOPARK) and established Parkinson's disease as a leading neurodegeneration indication for NAD+ therapeutics.

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