Nicotinamide riboside supplementation is not associated with altered methylation homeostasis in Parkinson’s disease

• Published in: iScience Vol. 26; no. 3; p. 106278
• Main Authors: Gaare, Johannes J., Dölle, Christian, Brakedal, Brage, Brügger, Kim, Haugarvoll, Kristoffer, Nido, Gonzalo S., Tzoulis, Charalampos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-03-2023; Elsevier
• Subjects: Biological sciences; Clinical neuroscience; Molecular neuroscience; Neuroscience; Molecular neuroscience; Neuroscience; Biological sciences; Clinical neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106278

Replenishing nicotinamide adenine dinucleotide (NAD) via supplementation of nicotinamide riboside (NR) has been shown to confer neuroprotective effects in models of aging and neurodegenerative diseases, including Parkinson’s disease (PD). Although generally considered safe, concerns have been raised that NR supplementation could impact methylation dependent reactions, including DNA methylation, because of increased production and methylation dependent breakdown of nicotinamide (NAM). We investigated the effect of NR supplementation on DNA methylation in a double blinded, placebo-controlled trial of 29 human subjects with PD, in blood cells and muscle tissue. Our results show that NR had no impact on DNA methylation homeostasis, including individuals with common pathogenic mutations in the MTHFR gene known to affect one-carbon metabolism. Pathway and methylation variance analyses indicate that there might be minor regulatory responses to NR. We conclude that short-term therapy with high-dose NR for up to 30 days has no deleterious impact on methylation homeostasis.
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•NR 1000 mg/day for 30 days does not alter the global DNA methylation profile in blood•NR does not impact DNA methylation in individuals carrying common MTHFR mutations•Pathway and methylation variance analyses indicate minor regulatory responses to NR
Biological sciences; Neuroscience; Molecular neuroscience; Clinical neuroscience