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

Curtis, Katrina; O’Brien, Katie A.; Tanner, Rebecca; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I.; Edwards, Lindsay M.; Hopkinson, Nicholas S

doi:10.1371/journal.pone.0144504

Cited by 46 publications

(72 citation statements)

References 51 publications

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“…This observation agrees with the observations in healthy older adults,33 PAD patients,19 and COPD patients 14,15,35. In contrast to these findings,14,15,33 we did not observe a reduction in SBP following NO 3 − supplementation.…”

Section: Discussionsupporting

confidence: 91%

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Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial

Friis¹,

Steenholt²,

Løkke³

et al. 2017

COPD

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Background and objectiveDietary beetroot juice (BR) supplementation has been shown to reduce the oxygen (O2) consumption of standardized exercise and reduce resting blood pressure (BP) in healthy individuals. However, the physiological response of BR in chronic obstructive pulmonary disease (COPD) remains controversial. The objective was to test exercise performance in COPD, supplementing with higher doses of BR for a longer duration compared to previous trials in this patient group.MethodsFifteen COPD patients consumed concentrated BR (2×70 mL twice daily, each containing 300 mg nitrate) or placebo (PL) (2×70 mL twice daily, nitrate-negligible) in a randomized order for 6 consecutive days. On day 7, participants consumed either BR or PL 150 min before testing. BP was measured before completing 6-minute walk test (6MWT) and two trials of submaximal cycling. The protocol was repeated after a minimum washout of 7 days.ResultsPlasma nitrite concentration was higher in the BR condition compared to PL (P<0.01). There was no difference between the BR and PL conditions regarding the covered distance during the 6MWT (mean ± standard error of the mean: 515±35 m (BR) vs 520±38 m (PL), P=0.46), O2 consumption of submaximal exercise (trial 1 P=0.31 vs trial 2 P=0.20), physical activity level (P>0.05), or systolic BP (P=0.80). However, diastolic BP (DBP) was reduced after BR ingestion compared to baseline (mean difference: 4.6, 95% CI: 0.1–9.1, P<0.05).ConclusionSeven days of BR ingestion increased plasma nitrite concentrations and lowered DBP in COPD patients. However, BR did not increase functional walking capacity, O2 consumption during submaximal cycling, or physical activity level during the intervention period.

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Section: Discussionsupporting

confidence: 91%

“…PAL measured in the present study corresponded with the previous measurements in COPD patients 35. Previous studies show that the effect of NO 3 − supplementation, if continuously supplemented, is maintained for 6–15 days in healthy individuals 16,18,28.…”

Section: Discussionsupporting

confidence: 89%

Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial

Friis¹,

Steenholt²,

Løkke³

et al. 2017

COPD

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“…Whilst Curtis et al . did not find any effect on endurance time at 70% of maximal workload of beetroot juice (12.9 mmol nitrate) ingested 3 hours beforehand, isotime oxygen consumption (VO 2 ) was 3–4% lower following nitrate supplementation . The arterial oxyHb saturations decreased from ~95–96% to ~93–94% with exercise.…”

Section: Does Nitrite Alter Mitochondrial Metabolism?mentioning

confidence: 86%

“…Leong et al found no effect of 3 days of beetroot juice (4.8 mmol twice a day) on the endurance shuttle walk test (ESWT) distance and time to fatigue at 85% VO 2,max in 19 patients with COPD [29]. Whilst Curtis et al did not find any effect on endurance time at 70% of maximal workload of beetroot juice (12.9 mmol nitrate) ingested 3 hours beforehand, isotime oxygen consumption (VO 2 ) was 3-4% lower following nitrate supplementation [30]. The arterial oxyHb saturations decreased from~95-96% to~93-94% with exercise.…”

Section: Does Nitrite Alter Mitochondrial Metabolism?mentioning

confidence: 98%

It is rocket science – why dietary nitrate is hard to ‘beet’! Part II: further mechanisms and therapeutic potential of the nitrate‐nitrite‐NO pathway

Mills

Khatri

Maskell

et al. 2016

Brit J Clinical Pharma

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Dietary nitrate (found in green leafy vegetables such as rocket and in beetroot) is now recognized to be an important source of nitric oxide, via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. Having described key twists and turns in the elucidation of the pathway and the underlying mechanisms in Part I, we explore the more recent developments which have served to confirm mechanisms, extend our understanding, and discover new properties and potential therapeutic uses of the pathway in Part II. Even the established dependency on low oxygen states for bioactivation of nitrite has recently been challenged. Dietary nitrate appears to be an important component of 'healthy diets', such as the DASH diet to lower blood pressure and the Mediterranean diet, with its potential to lower cardiovascular risk, possibly through beneficial interactions with a range of other constituents. The World Cancer Research Foundation report strong evidence for vegetables including spinach and lettuce (high nitrate-containing) decreasing cancer risk (mouth, pharynx, larynx, oesophagus and stomach), summarized in a 'NitrateCancer Risk Veg- Table'. The European Space Agency recommends that beetroot, lettuce, spinach and rocket (high-nitrate vegetables) are grown to provide food for long-term space missions. Nitrate, an ancient component of rocket fuel, could support sustainable crops for healthy humans. IntroductionIn Part I we described how the nitrate-nitrite-NO pathway was initially established. In Part II we address the more recent developments that have served to confirm mechanisms, extend our understanding, and discover new properties and potential therapeutic uses of the pathway. Is nitrate protective in ischaemia-reperfusion injury (IRI)?Having previously discovered the protective effects of inorganic nitrite in a model of ischaemia-reperfusion injury (IRI) in the isolated perfused rat heart (Langendorff preparation)

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“…At a whole body level, nitrate supplementation has been shown to decrease the O 2 cost of exercise in healthy subjects in both normoxic and hypoxic conditions [16][17][18][19][20], in a clinical population suffering from hypoxia as a result of chronic obstructive pulmonary disease [21], and also in subjects with decreased O 2 carrying capacity due to blood donation [22]. Once consumed, nitrate is believed to be reduced in a stepwise fashion, firstly to nitrite (NO 2 − ) and then to nitric oxide (NO) [23,24], adding to the endogenous production of NO from the NO synthasedependent oxidation of L-arginine [25].…”

Section: Introductionmentioning

confidence: 99%

PPARα-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia

O’Brien

Horscroft

Devaux

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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. (2018). PPAR-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE. https://doi.org/10.1016/j.bbadis.2018.07.027Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policyIf you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. A B S T R A C THypoxia is a feature of many disease states where convective oxygen delivery is impaired, and is known to suppress oxidative metabolism. Acclimation to hypoxia thus requires metabolic remodelling, however hypoxia tolerance may be aided by dietary nitrate supplementation. Nitrate improves tissue oxygenation and has been shown to modulate skeletal muscle tissue metabolism via transcriptional changes, including through the activation of peroxisome proliferator-activated receptor alpha (PPARα), a master regulator of fat metabolism. Here we investigated whether nitrate supplementation protects skeletal muscle mitochondrial function in hypoxia and whether PPARα is required for this effect. Wild-type and PPARα knockout (PPARα) mice were supplemented with sodium nitrate via the drinking water or sodium chloride as control, and exposed to environmental hypoxia (10% O 2 ) or normoxia for 4 weeks. Hypoxia suppressed mitochondrial respiratory function in mouse soleus, an effect partially alleviated through nitrate supplementation, but occurring independently of PPARα. Specifically, hypoxia resulted in 26% lower mass specific fatty acid-supported LEAK respiration and 23% lower pyruvate-supported oxidative phosphorylation capacity. Hypoxia also resulted in 24% lower citrate synthase activity in mouse soleus, possibly indicating a loss of mitochondrial content. These changes were not seen, however, in hypoxic mice when supplemented with dietary nitrate, indicating a nitrate dependent preservation of mitocho...

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

Cited by 46 publications

References 51 publications

Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial

Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial

It is rocket science – why dietary nitrate is hard to ‘beet’! Part II: further mechanisms and therapeutic potential of the nitrate‐nitrite‐NO pathway

PPARα-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia

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

Cited by 46 publications

References 51 publications

Dietary beetroot juice &ndash; effects on physical performance in COPD patients: a randomized controlled crossover trial

Dietary beetroot juice &ndash; effects on physical performance in COPD patients: a randomized controlled crossover trial

It is rocket science – why dietary nitrate is hard to ‘beet’! Part II: further mechanisms and therapeutic potential of the nitrate‐nitrite‐NO pathway

PPARα-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia

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Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial

Dietary beetroot juice – effects on physical performance in COPD patients: a randomized controlled crossover trial