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dc.contributor.authorBerven, Haakon
dc.contributor.authorKverneng, Simon Ulvenes
dc.contributor.authorSheard, Erika
dc.contributor.authorSøgnen, Mona
dc.contributor.authorAf Geijerstam, Solveig Amdahl
dc.contributor.authorHaugarvoll, Kristoffer
dc.contributor.authorSkeie, Geir Olve
dc.contributor.authorDölle, Christian
dc.contributor.authorTzoulis, Charalampos
dc.date.accessioned2024-05-30T07:20:42Z
dc.date.available2024-05-30T07:20:42Z
dc.date.created2023-12-20T09:38:14Z
dc.date.issued2023
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/11250/3131933
dc.description.abstractNicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of high-dose NR therapy, we conducted a single-center, randomized, placebo-controlled, double-blind, phase I trial on 20 individuals with PD, randomized 1:1 on NR 1500 mg twice daily (n = 10) or placebo (n = 10) for four weeks. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The primary outcome was safety, defined as the frequency of moderate and severe adverse events. Secondary outcomes were tolerability defined as frequency of mild adverse events, change in the whole blood and urine NAD metabolome, and change in the clinical severity of PD, measured by MDS-UPDRS. All 20 participants completed the trial. The trial met all prespecified outcomes. NR therapy was well tolerated with no moderate or severe adverse events, and no significant difference in mild adverse events. NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose. NR greatly augmented the blood NAD metabolome with up to 5-fold increase in blood NAD+ levels. While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact. Our results support extending the dose range of NR in phase II clinical trials to 3000 mg per day, with appropriate safety monitoring. Clinicaltrials.gov identifier: NCT05344404.en_US
dc.language.isoengen_US
dc.publisherNatureen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleNR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s diseaseen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.source.articlenumber7793en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1038/s41467-023-43514-6
dc.identifier.cristin2216044
dc.source.journalNature Communicationsen_US
dc.identifier.citationNature Communications. 2023, 14 (1), 7793.en_US
dc.source.volume14en_US
dc.source.issue1en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal