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

Thorax
Q1
Dec 2021
Citations:24
Influential Citations:2
Interventional (Human) Studies
93
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Enhanced Details

Methods
Single-centre, double-blind, placebo-controlled, randomized cross-over trial; adults with COPD requiring long-term oxygen therapy (LTOT); 20 participants completed.
Intervention
NR-BRJ: 140 mL nitrate-rich beetroot juice containing 12.9 mmol NO3-, ingested orally 3 hours before endurance shuttle walk test; placebo BRJ: 140 mL nitrate-depleted beetroot juice; single-dose per session; two dosing events per participant (NR-BRJ and PL-BRJ).
Results
Acute NR-BRJ supplementation increased endurance time on ESWT by a median 62 s vs placebo (NR-BRJ 194.6 s vs PL-BRJ 159.1 s; p<0.0001). Endothelial function improved with NR-BRJ: +4.1% vs -5.0% with placebo (p=0.0003). SpO2 AUC higher with NR-BRJ (estimated treatment effect 43.69; 95% CI 29.09-58.28; p<0.0001). HR AUC showed no significant difference. FE NO increased with NR-BRJ (area under the curve higher; p=0.0011). Plasma NO3- and NO2- rose substantially after NR-BRJ vs placebo (NO3- change ~550 µM; NO2- ~0.248 µM; p=0.0003 and p=0.0011 respectively). No significant changes in oxidative stress markers (FRAP, TBARS, total free thiols). Conclude that acute dietary nitrate supplementation with NR-BRJ improves exercise endurance and endothelial function in COPD patients on LTOT; longer-term dosing needed to determine clinical relevance.
Limitations
Small, single-centre, acute-dose study in a COPD phenotype with hypoxaemia requiring LTOT; short follow-up; incomplete data for some measures; generalizability to broader COPD populations or longer-term use unknown.

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 e...