Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study
What this study found
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…
- Study & population
- 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).
- Key limitation
- 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.
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Open PDFOriginal 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.