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

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217147
Author(s):  
Matthew J Pavitt ◽  
Adam Lewis ◽  
Sara C Buttery ◽  
Bernadette O Fernandez ◽  
Monika Mikus-Lelinska ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Area Under The Curve ◽  
Supplemental Oxygen ◽  
Test Time ◽  
Walk Test ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Double Blind Placebo ◽  
Nitrate Supplementation ◽  
Exercise Endurance

RationaleDietary 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.MethodsWe 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.MeasurementsThe 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 results20 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).ConclusionAcute dietary nitrate supplementation increases exercise endurance in patients with COPD who require supplemental oxygen.Trial registration numberISRCTN14888729.

scholarly journals Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study

Thorax ◽  
2020 ◽  
Vol 75 (7) ◽  
pp. 547-555
Author(s):  
Matthew J Pavitt ◽  
Rebecca Jayne Tanner ◽  
Adam Lewis ◽  
Sara Buttery ◽  
Bhavin Mehta ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Active Treatment ◽  
Treatment Effect ◽  
Pulmonary Rehabilitation ◽  
Activity Level ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Double Blind Placebo ◽  
Parallel Group ◽  
Nitrate Supplementation

RationaleDietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD.MethodsThis double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II–IV COPD and Medical Research Council dyspnoea score 3–5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation.MeasurementsThe primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters.Results165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group −5.0 mm Hg (−5.0, –3.0) versus control +6.0 mm Hg (−1.0, 15.5), estimated treatment effect −7 mm Hg (95% CI 7 to −20) (p<0.0005). No significant serious adverse events or side effects were reported.ConclusionsDietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD.Trial registration numberISRCTN27860457.

scholarly journals Acute Dietary Nitrate Supplementation and Exercise Performance in COPD: A Double-Blind, Placebo-Controlled, Randomised Controlled Pilot Study

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144504 ◽  
Author(s):  
Katrina J. Curtis ◽  
Katie A. O’Brien ◽  
Rebecca J. Tanner ◽  
Juliet I. Polkey ◽  
Magdalena Minnion ◽  
...  
Keyword(s):  
Pilot Study ◽  
Exercise Performance ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Double Blind Placebo ◽  
Nitrate Supplementation ◽  
Randomised Controlled

scholarly journals Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study

2018 ◽  
Vol 118 (01) ◽  
pp. 112-122 ◽  
Author(s):  
Nicholas Burnley-Hall ◽  
Fairoz Abdul ◽  
Vitaliy Androshchuk ◽  
Keith Morris ◽  
Nick Ossei-Gerning ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Extracellular Vesicles ◽  
Controlled Study ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Double Blind Placebo ◽  
Clopidogrel Therapy ◽  
Nitrate Supplementation ◽  
Artery Disease

AbstractExtracellular vesicles (EVs) are implicated in the pathogenesis of cardiovascular disease (CVD). Specifically, platelet-derived EVs are highly pro-coagulant, promoting thrombin generation and fibrin clot formation. Nitrate supplementation exerts beneficial effects in CVD, via an increase in nitric oxide (NO) bioavailability. Clopidogrel is capable of producing NO-donating compounds, such as S-nitrosothiols (RSNO) in the presence of nitrite and low pH. The aim of this study was to assess the effect of nitrate supplementation with versus without clopidogrel therapy on circulating EVs in coronary artery disease (CAD) patients. In this randomized, double-blind, placebo-controlled study, CAD patients with (n = 10) or without (n = 10) clopidogrel therapy received a dietary nitrate supplement (SiS nitrate gel) or identical placebo. NO metabolites and platelet activation were measured using ozone-based chemiluminescence and multiple electrode aggregometry. EV concentration and origin were determined using nanoparticle tracking analysis and time-resolved fluorescence. Following nitrate supplementation, plasma RSNO was elevated (4.7 ± 0.8 vs 0.2 ± 0.5 nM) and thrombin-receptor mediated platelet aggregation was reduced (−19.9 ± 6.0 vs 4.0 ± 6.4 U) only in the clopidogrel group compared with placebo. Circulating EVs were significantly reduced in this group (−1.183e11 ± 3.15e10 vs −9.93e9 ± 1.84e10 EVs/mL), specifically the proportion of CD41+ EVs (−2,120 ± 728 vs 235 ± 436 RFU [relative fluorescence unit]) compared with placebo. In vitro experiments demonstrated clopidogrel–SNO can reduce platelet-EV directly (6.209e10 ± 4.074e9 vs 3.94e11 ±  1.91e10 EVs/mL). In conclusion, nitrate supplementation reduces platelet-derived EVs in CAD patients on clopidogrel therapy, increasing patient responsiveness to clopidogrel. Nitrate supplementation may represent a novel approach to moderating the risk of thrombus formation in CAD patients.

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