Nature and Science of Sleep (Mar 2021)
Effect of Dietary Nitrate Supplementation on Sleep in Chronic Obstructive Pulmonary Disease Patients
Abstract
Jonathan P Wisor, 1 Nils Henrik Holmedahl, 2 Ingvild West Saxvig, 3 Odd-Magne Fjeldstad, 2 Eddie Weitzberg, 4 Janne Grønli, 5 Harald Kåre Engan 6 1Sleep and Performance Research Center and Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 2Section of Lung Rehabilitation, Department of Rehabilitation and Lifestyle Medicine, LHL-Hospital Gardermoen, Jessheim, Norway; 3Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 4Department of Physiology and Pharmacology, Karolinska Institutet and Department of Perioperative Medicine and Intensive Care, Karolinska Hospital, Stockholm, Sweden; 5Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Bergen, Norway; 6Unicare Rehabilitation, Oslo, NorwayCorrespondence: Jonathan P WisorWashington State University, 412 E. Spokane Falls Blvd, Spokane, WA, 99202, USATel +1 509358-7577Email [email protected]: Poor sleep quality in chronic obstructive pulmonary disease (COPD) is a result of oxygen desaturation secondary to compromised lung function. Nitrate supplementation with dietary beetroot juice is known to elevate plasma nitrate and to increase the efficiency of oxygen utilization in non-COPD individuals; whether it is of therapeutic benefit for sleep quality in COPD has not been reported.Patients and Methods: In a counterbalanced within-subjects design involving 15 COPD patients as subjects, the subjects consumed either beetroot juice containing nitrate (BJ; ∼ 6.2 mmol NO 3–) or placebo (NO 3– -depleted juice) immediately before a night of polysomnographic monitoring. Nitrate was measured in plasma collected immediately after waking.Results: While BJ consumption had no effect on the amount of time spent in any sleep stages, wake-to-N2 transitions and direct wake-to-rapid eye movement sleep (REMS) transitions, hallmarks of disordered sleep, were less frequent on the BJ night than on the placebo night. In the last two hours of the BJ night, percent time in REMS increased and delta power during deep (N3) non-REMS decreased, relative to the placebo night. Collectively, the reduced frequency of atypical transitions and the normalization of non-REMS/REMS dynamics after BJ are indicative of an improvement of sleep quality. BJ also resulted in sustained elevation of peripheral oxygen saturation (SpO 2), during episodes of wake after sleep onset. Plasma nitrate was elevated nearly tenfold on the morning after BJ relative to placebo.Conclusion: BJ has a normalizing effect on disordered sleep in COPD, which may be related to improved oxygen delivery.Clinical Trial Registration: The activities of the Regional Committees for Medical and Health Research Ethics (REC) are founded on the Norwegian law on research ethics and medical research. This study was approved by NTNU/REK midt, Det medisinske fakultet, Postboks 8905, 7491 Trondheim (REK midt 2016/1360).Keywords: polysomnography, oxygen saturation, beetroot juice, hypoxia