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

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 . Drivers of physiological aging are also linked to the etiology of chronic obstructive pulmonary disease (COPD), including inflammation and senescence, both influenced by nicotinamide adenine dinucleotide (NAD + ) metabolism. Norheim et al. performed a randomized controlled trial in patients with COPD, testing whether boosting NAD + levels reduces airway inflammation.