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

Johannes J Gaare; Christian Dölle; Brage Brakedal; Kim Brügger; Kristoffer Haugarvoll; Gonzalo S Nido; Charalampos Tzoulis

doi:10.1016/j.isci.2023.106278

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

iScience. 2023 Feb 27;26(3):106278. doi: 10.1016/j.isci.2023.106278. eCollection 2023 Mar 17.

Authors

Johannes J Gaare^{1

2

3}, Christian Dölle^{1

2

3}, Brage Brakedal^{1

2

3}, Kim Brügger^{1

2

3}, Kristoffer Haugarvoll^{1

2

3}, Gonzalo S Nido^{1

2

3}, Charalampos Tzoulis^{1

2

3}

Affiliations

¹ Neuro-SysMed Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
² K.G Jebsen Center for Translational Research in Parkinson's Disease, University of Bergen, Bergen, Norway.
³ Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Abstract

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.

Keywords: Biological sciences; Clinical neuroscience; Molecular neuroscience; Neuroscience.