A double blind randomized placebo control crossover trial on the effect of dietary nitrate supplementation on exercise tolerance in stable moderate chronic obstructive pulmonary disease

Design: double-blind, computer-randomized, placebo-controlled crossover trial at a tertiary Australian hospital. Participants: adults with stable moderate COPD (GOLD II), aged 45-80; 35 enrolled, 23 completed safety phase, 19 completed all four visits (14 female, 5 male).

Beetroot juice containing nitrate; 70 mL per dose delivering 4.8 mmol NO3−; taken orally twice daily for three days prior to endurance shuttle walk testing, with a final dose on the morning of testing.

BR nitrate did not significantly improve endurance: ESWT distance increased by 11% (79 m) but p = 0.494; ESWT time to fatigue increased by 0.6 minutes (6%) but p = 0.693. Distances were 721.6 ± 587.5 m on placebo vs 800.0 ± 584.3 m on BR. Safety: resting systolic BP decreased by ~10 mmHg at 1 hour; one participant developed symptomatic postural hypotension and was excluded; diastolic BP and dyspnea scores showed no significant changes. Conclusion: Routine acute dietary nitrate supplementation with BR is not supported to enhance submaximal exercise endurance in moderate COPD; observed BP-lowering effect warrants caution and further larger, targeted studies to identify responders and dose–response.

High attrition (35 enrolled; 19 completed); no biochemical verification of nitrate/nitrite levels; no plasma measures to confirm exposure or kinetics; relatively small sample with large variability; potential carryover effects in a crossover design; limited generalizability to COPD phenotypes beyond GOLD II; potential hypotension risk with nitrate supplementation.