Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo-controlled trial.

Autor: Norheim KL; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Ben Ezra M; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark., Heckenbach I; Buck Institute for Research on Aging, Novato, CA, USA., Andreasson LM; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Eriksen LL; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Dyhre-Petersen N; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Damgaard MV; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Berglind M; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark., Pricolo L; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark., Sampson D; Elysium Health, New York, NY, USA., Dellinger RW; Elysium Health, New York, NY, USA., Sverrild A; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Treebak JT; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ditlev SB; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Porsbjerg C; Department of Respiratory Medicine and Infectious Diseases, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Copenhagen Center for Translational Research, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark., Scheibye-Knudsen M; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark. mscheibye@sund.ku.dk.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2024 Nov 15. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1038/s43587-024-00758-1
Abstrakt: Chronic obstructive pulmonary disease (COPD) is a progressive, incurable disease associated with smoking and advanced age, ranking as the third leading cause of death worldwide. DNA damage and loss of the central metabolite nicotinamide adenine dinucleotide (NAD + ) may contribute to both aging and COPD, presenting a potential avenue for interventions. In this randomized, double-blind, placebo-controlled clinical trial, we treated patients with stable COPD (n = 40) with the NAD + precursor nicotinamide riboside (NR) for 6 weeks and followed-up 12 weeks later. The primary outcome was change in sputum interleukin-8 (IL-8) from baseline to week 6. The estimated treatment difference between NR and placebo in IL-8 after 6 weeks was -52.6% (95% confidence interval (CI): -75.7% to -7.6%; P = 0.030). This effect persisted until the follow-up 12 weeks after the end of treatment (-63.7%: 95% CI -85.7% to -7.8%; P = 0.034). For secondary outcomes, NR treatment increased NAD + levels by more than twofold in whole blood, whereas IL-6 levels in plasma remained unchanged. In exploratory analyses, treatment with NR showed indications of upregulated gene pathways related to genomic integrity in the airways and reduced epigenetic aging, possibly through a reduction in cellular senescence. These exploratory analyses need to be confirmed in future trials. ClinicalTrials.gov identifier: NCT04990869 .
Competing Interests: Competing interests D.S. and R.W.D. are employees of Elysium Health and own shares in the company. The other authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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