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 beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study

2017 ◽  
Vol 313 (1) ◽  
pp. H59-H65 ◽  
Author(s):  
Karambir Notay ◽  
Anthony V. Incognito ◽  
Philip J. Millar
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sympathetic Outflow ◽  
Beetroot Juice ◽  
Proof Of Concept ◽  
Burst Frequency ◽  
Double Blind ◽  
Dietary Nitrate ◽  
Nitrate Supplementation ◽  
Central Sympathetic Outflow

Acute dietary nitrate ([Formula: see text]) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary [Formula: see text] supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) ingestion of 70ml high-[Formula: see text] (~6.4 mmol [Formula: see text]) BR or [Formula: see text]-depleted BR placebo (PL; ~0.0055 mmol [Formula: see text]) in a double-blind, randomized, crossover design. Blood pressure and MSNA were also collected during 2 min of static handgrip (30% maximal voluntary contraction). The changes in resting MSNA burst frequency (−3 ± 5 vs. 3 ± 4 bursts/min, P = 0.001) and burst incidence (−4 ± 7 vs. 4 ± 5 bursts/100 heart beats, P = 0.002) were lower after BR versus PL, whereas systolic blood pressure (−1 ± 5 vs. 2 ± 5 mmHg, P = 0.30) and diastolic blood pressure (4 ± 5 vs. 5 ± 7 mmHg, P = 0.68) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95) were not different. During static handgrip, the change in MSNA burst incidence (1 ± 8 vs. 8 ± 9 bursts/100 heart beats, P = 0.04) was lower after BR versus PL, whereas MSNA burst frequency (6 ± 6 vs. 11 ± 10 bursts/min, P = 0.11) as well as systolic blood pressure (11 ± 7 vs. 12 ± 8 mmHg, P = 0.94) and diastolic blood pressure (11 ± 4 vs. 11 ± 4 mmHg, P = 0.60) were not different. Collectively, these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise. Dietary [Formula: see text] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical populations. NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease.

scholarly journals ACUTE DIETARY NITRATE SUPPLEMENTATION FAILS TO IMPROVE EXERCISE ECONOMY IN ELDERLY

2017 ◽  
pp. 1-4
Author(s):  
M. Driller ◽  
L. Thompson ◽  
J. McQuillan ◽  
R. Masters
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Perceived Exertion ◽  
Double Blind ◽  
Walking Test ◽  
Dietary Nitrate ◽  
Exercise Economy ◽  
Nitrate Supplementation ◽  
Walking Economy ◽  
Experimental Trials

Objective: Improvements in exercise economy following dietary nitrate (NO3-) supplementation in young, athletic populations has been well documented, but little research has focused on whether these same benefits translate to elderly populations. Design: Participants completed two experimental trials in a double-blind, randomized, crossover design. Setting: University laboratory. Participants: Twenty-one elderly participants >65 yr (10 male/11 female, mean ± SD; age: 72 ± 6 yr). Intervention: Each trial consisted of participants ingesting a 70ml dose of either NO3- rich (NIT; 5.0mmol.L-1) or NO3- depleted (PLA; 0.003mmol.L-1) beetroot juice two hours prior to reporting to the laboratory. Measurements: On arrival at the laboratory, blood pressure was assessed followed by a five minute walking economy test on a treadmill (3km.h-1 and 1% gradient). VO2, heart rate and RPE were monitored during the walking test. Results: There were no significant differences (p > 0.05) between NIT and PLA trials for any of the measured variables during the walking test. Furthermore, no differences were found for blood pressure between trials. All results were associated with trivial or unclear effect sizes. Conclusion: Despite recent reports of improved exercise economy in young, athletic populations following NO3- supplementation, the current study did not find any benefit to sub-maximal VO2, heart rate, perceived exertion or blood pressure in elderly participants when performing a 5-minute walk following NO3- supplementation.

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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