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

Abstract

Background: Dietary nitrate supplementation has been shown to decrease the oxygen cost of exercise and prolong exercise tolerance, as measured by sub-maximal exercise endurance distance and time at 85% V̇O2max, in both elite athletes and normal healthy subjects. Patients with chronic obstructive pulmonary disease (COPD) have reduced quality of life and ability to perform activities of daily living attributable to diminished exercise tolerance, and dietary nitrate may be able to ameliorate this.

Methods: We performed a double-blind, computer-randomized placebo control crossover trial at a tertiary Australian hospital to investigate whether dietary nitrate supplementation as beetroot juice (BR) would augment submaximal exercise endurance in individuals with spirometrically confirmed stable moderate COPD. Volunteers underwent an incremental shuttle walk test to determine V̇O2max followed by a test dose of BR to establish safety in the study population. Participants performed an endurance shuttle walk test (ESWT) at 85% V̇O2max after randomization to either a 3 day wash-in of BR (4.8 mmol twice a day) or placebo (nitrate deplete BR), with a final dose on the morning of testing. They then crossed over after 4 day washout. Repeated measures two sided paired t-tests were employed.

Results: 35 participants were recruited with 19 completing the trial. In the initial safety phase, we measured systolic blood pressure over four hours post first dose of BR, and found a mean 10 mmHg decrement maximal at 1 hour. One individual developed symptomatic postural hypotension and was excluded. The primary outcomes of ESWT distance and time to fatigue improved by 11% and 6% respectively; however these differences did not achieve statistical significance (p = 0.494 and 0.693 respectively).

Conclusions: Our study does not support a role for routine dietary nitrate supplementation for enhancement of exercise endurance in COPD.

Trial registration: Australia and New Zealand Clinical Trial Register: ACTRN12611001088932.

Figures

Figure 1

Study design. Visits 1 and 2 occurred approximately 1 week apart and collected baseline and safety data on participants. Visits 3 and 4 were exactly 7 days apart per study protocol. Prior to visit 3, participants consumed either beetroot (BR) or placebo (PL) twice a day for three days. They underwent an endurance shuttle walk test during visit 3 and then abstained from BR for 4 days to allow washout. In the crossover phase, participants were given to whichever juice (BR or PL) they had not previously been exposed to. This was taken twice a day for three days prior to visit 4, at which time another endurance shuttle walk test was performed.

Figure 2

ESWT distance change. Figure 2a: Plot of individual participants’ endurance shuttle walk test (ESWT) distances (n = 19). Figure 2b: Box and stem plots of individual participants’ endurance shuttle walk test (ESWT) (n = 19). Abbreviations: BR: beetroot juice, PL: placebo.