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Original research
Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study
  1. Matthew J Pavitt1,
  2. Adam Lewis1,
  3. Sara C Buttery1,
  4. Bernadette O Fernandez2,
  5. Monika Mikus-Lelinska2,
  6. Winston A S Banya1,
  7. Martin Feelisch3,4,
  8. Michael I Polkey1,5,
  9. Nicholas S Hopkinson1
  1. 1National Heart and Lung Institute, Imperial College London, London, UK
  2. 2Clinical and Experimental Sciences, Southampton Hospital, Southampton, UK
  3. 3Faculty of Medicine, Clinical and Experimental Sciences, University of Southampton, Southampton, UK
  4. 4Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK
  5. 5Respiratory Medicine, Royal Brompton Hospital, London, UK
  1. Correspondence to Professor Nicholas S Hopkinson, National Heart and Lung Institute, Imperial College London, London SW7 2BX, UK; n.hopkinson{at}ic.ac.uk

Abstract

Rationale Dietary nitrate supplementation improves skeletal muscle oxygen utilisation and vascular endothelial function. We hypothesised that these effects might be sufficient to improve exercise performance in patients with COPD and hypoxia severe enough to require supplemental oxygen.

Methods We conducted a single-centre, double-blind, placebo-controlled, cross-over study, enrolling adults with COPD who were established users of long-term oxygen therapy. Participants performed an endurance shuttle walk test, using their prescribed oxygen, 3 hours after consuming either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate) or placebo (nitrate-depleted BRJ). Treatment order was allocated (1:1) by computer-generated block randomisation.

Measurements The primary outcome was endurance shuttle walk test time. The secondary outcomes included area under the curve to isotime for fingertip oxygen saturation and heart rate parameters during the test, blood pressure, and endothelial function assessed using flow-mediated dilatation. Plasma nitrate and nitrite levels as well as FENO were also measured.

Main results 20 participants were recruited and all completed the study. Nitrate-rich BRJ supplementation prolonged exercise endurance time in all participants as compared with placebo: median (IQR) 194.6 (147.5–411.7) s vs 159.1 (121.9–298.5) s, estimated treatment effect 62 (33–106) s (p<0.0001). Supplementation also improved endothelial function: NR-BRJ group +4.1% (−1.1% to 14.8%) vs placebo BRJ group −5.0% (−10.6% to –0.6%) (p=0.0003).

Conclusion Acute dietary nitrate supplementation increases exercise endurance in patients with COPD who require supplemental oxygen.

Trial registration number ISRCTN14888729.

  • exercise
  • COPD pharmacology
  • long term oxygen therapy (LTOT)

Data availability statement

Data are available upon reasonable request. Individual participant data that underlie the results in the article after de-identification (text, tables, figures and appendices) will be made available from the corresponding author upon request. The study protocol and statistical analysis plan will also be available. Data will be available indefinitely.

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Data availability statement

Data are available upon reasonable request. Individual participant data that underlie the results in the article after de-identification (text, tables, figures and appendices) will be made available from the corresponding author upon request. The study protocol and statistical analysis plan will also be available. Data will be available indefinitely.

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Footnotes

  • Twitter @DrMattPav, @apl104, @COPDdoc

  • Contributors NSH and MIP developed the original idea for the research study. NSH and MJP designed and wrote the study protocol. WASB designed the statistical analysis plan. MJP, AL and SCB undertook patient visits and collected trial data. MF, BOF and MM-L undertook plasma analysis. MJP analysed the data and wrote the first draft of the manuscript. All authors edited and contributed to the final manuscript. NSH is the guarantor.

  • Funding The study was funded by a grant from Moulton Charitable Foundation.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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