Oxygen utilisation during exercise – a potential therapeutic target in chronic obstructive pulmonary disease

Abstract

This thesis addresses the impact of nitrate supplementation in the form of beetroot juice as a potential therapeutic intervention to improve exercise capacity in people with chronic obstructive pulmonary disease (COPD). Dietary nitrate supplementation can enhance levels of plasma nitrite (NO2-), nitrate (NO3-) and nitric oxide (NO). Nitric oxide is a ubiquitous signalling molecule with impacts on systemic and pulmonary vasculature. It also effects skeletal muscle oxygen consumption.

Within this thesis, I set out the background and evidence so far for NO3-supplementation in healthy individuals and those with COPD. To date studies have been small, with some conflicting findings. Specific potential responder phenotypes have not been selected for trials.

I undertook a randomised controlled trial, comparing the effect of 140 mLs concentrated nitrate-rich beetroot juice (NR-BRJ) cut with organic lemon juice (2%) containing 0.8 g (12.9 mmol) NO3- (140 mL BEET-IT® SPORT Shot, James White Drinks, Ipswich, UK) against a placebo (PL-BRJ) beverage which was otherwise identical, except that the NO3- had been removed by passage through an ion exchange column. Participants with COPD consumed one or other beverage before each session of an eight-week pulmonary rehabilitation programme. Data were available for 122 study completers. The median (IQR) improvement in the ISWT distance following PR was statistically greater with NO3--rich NR-BRJ than PL-BRJ, increasing by 60 (10, 85)m compared to 30 (0, 70)m, an estimated treatment effect 30 m (95%CI: 10, 40); p = 0.027.

In a single dose cross–over study in individuals with COPD who were established on long term oxygen therapy, endurance shuttle walk time was statistically significantly longer with NO3- supplementation compared to placebo 194.6 (147.5, 411.7)sec vs 159 (121.9, 298.5)sec, estimated treatment effect 62 sec (95%CI: 33, 106); p 0.0009.

I also demonstrated that NO3- supplementation was associated with a fall in blood pressure and an improvement in endothelial function, assessed using flow-mediated dilatation.

Dietary NO3- supplementation enhances exercise performance in hypoxic individuals with COPD and augments the effects of pulmonary rehabilitation. There may also be effects that are beneficial for cardiovascular co-morbidities which are extremely common in COPD.