Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC, a randomised controlled trial

Ali M Alasmari; Abdullah S Alsulayyim; Saeed M Alghamdi; Keir E J Philip; Sara C Buttery; Winston A S Banya; Michael I Polkey; Paul C Armstrong; Matthew J Rickman; Timothy D Warner; Jane A Mitchell; Nicholas S Hopkinson

doi:10.1183/13993003.02353-2022

Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC, a randomised controlled trial

Eur Respir J. 2024 Feb 1;63(2):2202353. doi: 10.1183/13993003.02353-2022. Print 2024 Feb.

Authors

Ali M Alasmari^{1

2}, Abdullah S Alsulayyim^{1

3}, Saeed M Alghamdi⁴, Keir E J Philip^{1

5}, Sara C Buttery¹, Winston A S Banya¹, Michael I Polkey^{1

5}, Paul C Armstrong⁶, Matthew J Rickman⁷, Timothy D Warner⁶, Jane A Mitchell⁷, Nicholas S Hopkinson⁸

Affiliations

¹ National Heart and Lung Institute, Royal Brompton Campus, Imperial College London, London, UK.
² Respiratory Therapy Department, College of Medical Rehabilitation Sciences, Taibah University, Madinah, Saudi Arabia.
³ Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.
⁴ Clinical Technology Department, Umm Al-Qura University, Makkah, Saudi Arabia.
⁵ Respiratory Medicine, Royal Brompton and Harefield Hospitals, London, UK.
⁶ Centre for Immunobiology, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁷ National Heart and Lung Institute, Cardiothoracic Pharmacology, Vascular Biology, Imperial College London, London, UK.
⁸ National Heart and Lung Institute, Royal Brompton Campus, Imperial College London, London, UK n.hopkinson@ic.ac.uk.

Abstract

Background: Short-term studies suggest that dietary nitrate (NO₃ ^-) supplementation may improve the cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice (NR-BRJ) is a convenient dietary source of nitrate.

Methods: The ON-BC trial was a randomised, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomisation to either 70 mL NR-BRJ (400 mg NO₃ ^-) (n=40) or an otherwise identical nitrate-depleted placebo juice (0 mg NO₃ ^-) (n=41), once daily for 12 weeks. The primary end-point was between-group change in home SBP measurement. Secondary outcomes included change in 6-min walk distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index normalised to a heart rate of 75 beats·min^-1 (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured.

Results: Compared with placebo, active treatment lowered SBP (Hodges-Lehmann treatment effect -4.5 (95% CI -5.9- -3.0) mmHg), and improved 6MWD (30.0 (95% CI 15.7-44.2) m; p<0.001), RHI (0.34 (95% CI 0.03-0.63); p=0.03) and AIx75 (-7.61% (95% CI -14.3- -0.95%); p=0.026).

Conclusions: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity.

Publication types

Randomized Controlled Trial

MeSH terms

Antioxidants
Blood Pressure
Cardiovascular Diseases* / drug therapy
Cardiovascular Diseases* / prevention & control
Cross-Over Studies
Dietary Supplements
Double-Blind Method
Humans
Nitrates / therapeutic use
Pulmonary Disease, Chronic Obstructive* / complications
Pulmonary Disease, Chronic Obstructive* / drug therapy
Risk Factors

Substances

Nitrates
Antioxidants