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Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study

Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study
Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study

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.

0040-6376
Pavitt, Matthew J
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Lewis, Adam
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Buttery, Sara C
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Fernandez, Bernadette O
9890aabc-1fe6-4530-a51e-31182e537131
Mikus-Lelinska, Monika
6ca48669-ff8f-4ae8-9d10-98c74327b4ec
Banya, Winston A S
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Feelisch, Martin
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Polkey, Michael I
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Hopkinson, Nicholas S
91e9a2af-8ab3-4671-b766-761e82bd5310
Pavitt, Matthew J
a6996d07-1c55-40f0-9ef4-fc2c736e7306
Lewis, Adam
1bc0b179-61ad-4a99-ba73-dc78e6e181b2
Buttery, Sara C
a93f2fbc-4c73-4b9d-82c0-95a19a8b6aa0
Fernandez, Bernadette O
9890aabc-1fe6-4530-a51e-31182e537131
Mikus-Lelinska, Monika
6ca48669-ff8f-4ae8-9d10-98c74327b4ec
Banya, Winston A S
3a658917-e227-423f-84b7-cc898c0cb9f7
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Polkey, Michael I
4f841dc9-9b94-4021-bbfc-64092cddc7b6
Hopkinson, Nicholas S
91e9a2af-8ab3-4671-b766-761e82bd5310

Pavitt, Matthew J, Lewis, Adam, Buttery, Sara C, Fernandez, Bernadette O, Mikus-Lelinska, Monika, Banya, Winston A S, Feelisch, Martin, Polkey, Michael I and Hopkinson, Nicholas S (2021) Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study. Thorax. (doi:10.1136/thoraxjnl-2021-217147).

Record type: Article

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.

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EDEN-Ox Manuscript symplectic 5-11-21 - Accepted Manuscript
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Accepted/In Press date: 4 November 2021
e-pub ahead of print date: 1 December 2021

Identifiers

Local EPrints ID: 454935
URI: http://eprints.soton.ac.uk/id/eprint/454935
ISSN: 0040-6376
PURE UUID: 5b1ed126-ac3b-43d0-bfd4-d19de5ab3f17
ORCID for Bernadette O Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 02 Mar 2022 17:30
Last modified: 17 Mar 2024 07:02

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Contributors

Author: Matthew J Pavitt
Author: Adam Lewis
Author: Sara C Buttery
Author: Bernadette O Fernandez ORCID iD
Author: Monika Mikus-Lelinska
Author: Winston A S Banya
Author: Martin Feelisch ORCID iD
Author: Michael I Polkey
Author: Nicholas S Hopkinson

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