NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease
Abstract Nicotinamide 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....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43514-6 |
| _version_ | 1797414529031733248 |
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| author | Haakon Berven Simon Kverneng Erika Sheard Mona Søgnen Solveig Amdahl Af Geijerstam Kristoffer Haugarvoll Geir-Olve Skeie Christian Dölle Charalampos Tzoulis |
| author_facet | Haakon Berven Simon Kverneng Erika Sheard Mona Søgnen Solveig Amdahl Af Geijerstam Kristoffer Haugarvoll Geir-Olve Skeie Christian Dölle Charalampos Tzoulis |
| author_sort | Haakon Berven |
| collection | DOAJ |
| description | Abstract Nicotinamide 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. |
| first_indexed | 2024-03-09T05:34:37Z |
| format | Article |
| id | doaj.art-93fb9663487c47aca79748e329682652 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T05:34:37Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-93fb9663487c47aca79748e3296826522023-12-03T12:29:39ZengNature PortfolioNature Communications2041-17232023-11-0114111310.1038/s41467-023-43514-6NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s diseaseHaakon Berven0Simon Kverneng1Erika Sheard2Mona Søgnen3Solveig Amdahl Af Geijerstam4Kristoffer Haugarvoll5Geir-Olve Skeie6Christian Dölle7Charalampos Tzoulis8Neuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalNeuro-SysMed, Department of Neurology, Haukeland University HospitalAbstract Nicotinamide 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.https://doi.org/10.1038/s41467-023-43514-6 |
| spellingShingle | Haakon Berven Simon Kverneng Erika Sheard Mona Søgnen Solveig Amdahl Af Geijerstam Kristoffer Haugarvoll Geir-Olve Skeie Christian Dölle Charalampos Tzoulis NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease Nature Communications |
| title | NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease |
| title_full | NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease |
| title_fullStr | NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease |
| title_full_unstemmed | NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease |
| title_short | NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease |
| title_sort | nr safe a randomized double blind safety trial of high dose nicotinamide riboside in parkinson s disease |
| url | https://doi.org/10.1038/s41467-023-43514-6 |
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