scholarly journals Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake kinetics, and exercise tolerance at high but not low pedal rates

2015 ◽  
Vol 118 (11) ◽  
pp. 1396-1405 ◽  
Author(s):  
Stephen J. Bailey ◽  
Richard L. Varnham ◽  
Fred J. DiMenna ◽  
Brynmor C. Breese ◽  
Lee J. Wylie ◽  
...  

We tested the hypothesis that inorganic nitrate (NO3−) supplementation would improve muscle oxygenation, pulmonary oxygen uptake (V̇o2) kinetics, and exercise tolerance (Tlim) to a greater extent when cycling at high compared with low pedal rates. In a randomized, placebo-controlled cross-over study, seven subjects (mean ± SD, age 21 ± 2 yr, body mass 86 ± 10 kg) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3−-rich beetroot juice (BR) (providing 8.4 mmol NO3−/day) and placebo (PLA). Compared with PLA, plasma nitrite concentration increased 178% with BR ( P < 0.01). There were no significant differences in muscle oxyhemoglobin concentration ([O2Hb]), phase II V̇o2 kinetics, or Tlim between BR and PLA when cycling at 35 rpm ( P > 0.05). However, when cycling at 115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II V̇o2 kinetics was faster (47 ± 16 s vs. 61 ± 25 s; P < 0.05), and Tlim was greater (362 ± 137 s vs. 297 ± 79 s; P < 0.05) with BR compared with PLA. These results suggest that short-term BR supplementation can increase muscle oxygenation, expedite the adjustment of oxidative metabolism, and enhance exercise tolerance when cycling at a high, but not a low, pedal cadence in healthy recreationally active subjects. These findings support recent observations that NO3− supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers.

2017 ◽  
Vol 49 (5S) ◽  
pp. 936
Author(s):  
Brynmor C. Breese ◽  
Stuart P. Cocksedge ◽  
Christopher Thompson ◽  
Lee J. Wylie ◽  
Anni V. Vanhatalo ◽  
...  

2017 ◽  
Author(s):  
Mary N. Woessner ◽  
Itamar Levinger ◽  
Christopher Neil ◽  
Cassandra Smith ◽  
Jason D Allen

BACKGROUND Chronic heart failure is characterized by an inability of the heart to pump enough blood to meet the demands of the body, resulting in the hallmark symptom of exercise intolerance. Chronic underperfusion of the peripheral tissues and impaired nitric oxide bioavailability have been implicated as contributors to the decrease in exercise capacity in these patients. nitric oxide bioavailability has been identified as an important mediator of exercise tolerance in healthy individuals, but there are limited studies examining the effects in patients with chronic heart failure. OBJECTIVE The proposed trial is designed to determine the effects of chronic inorganic nitrate supplementation on exercise tolerance in both patients with heart failure preserved ejection fraction (HFpEF) and heart failure reduced ejection fraction (HFrEF) and to determine whether there are any differential responses between the 2 cohorts. A secondary objective is to provide mechanistic insights into the 2 heart failure groups’ exercise responses to the nitrate supplementation. METHODS Patients with chronic heart failure (15=HFpEF and 15=HFrEF) aged 40 to 85 years will be recruited. Following an initial screen cardiopulmonary exercise test, participants will be randomly allocated in a double-blind fashion to consume either a nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo (for 5 days). Participants will continue daily dosing until the completion of the 4 testing visits (maximal cardiopulmonary exercise test, submaximal exercise test with echocardiography, vascular function assessment, and vastus lateralis muscle biopsy). There will then be a 2-week washout period after which the participants will cross over to the other treatment and complete the same 4 testing visits. RESULTS This study is funded by National Heart Foundation of Australia and Victoria University. Enrolment has commenced and the data collection is expected to be completed in mid 2018. The initial results are expected to be submitted for publication by the end of 2018. CONCLUSIONS If inorganic nitrate supplementation can improve exercise tolerance in patients with chronic heart failure, it has the potential to aid in further refining the treatment of patients in this population. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12615000906550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368912 (Archived by WebCite at http://www.webcitation.org/6xymLMiFK)


2020 ◽  
Vol 128 (5) ◽  
pp. 1355-1364 ◽  
Author(s):  
Mary N. Woessner ◽  
Christopher Neil ◽  
Nicholas J. Saner ◽  
Craig A. Goodman ◽  
Luke C. McIlvenna ◽  
...  

This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.


2020 ◽  
Vol 52 (7S) ◽  
pp. 341-341
Author(s):  
Jason D. Allen ◽  
Christopher Neil ◽  
Luke C. McIlvenna ◽  
Joaquin Ortiz de Zevallos ◽  
Itamar Levinger ◽  
...  

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 428-428
Author(s):  
Nicole Litwin ◽  
Scott Wrigley ◽  
Hannah Van Ark ◽  
Shannon Hartley ◽  
Kiri Michell ◽  
...  

Abstract Objectives Dietary inorganic nitrate from foods such as red beetroot juice (RBJ) can contribute to nitric oxide (NO) bioavailability through the enterosalivary nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by oral bacteria. We investigated the effects of inorganic nitrate supplementation, as RBJ or placebo + potassium nitrate (PBO+NIT), on the oral microbiota, and its relationship with saliva and plasma NO metabolites and vascular endothelial function. Methods In a randomized, double-blind, placebo-controlled trial, we measured the abundance of oral nitrate-reducing bacteria in saliva samples from 15 middle-aged/older adults with overweight and obesity using 16 rRNA sequencing. We also assessed the relationship of oral nitrate-reducing bacteria with the physiological responses to acute (4 hours) and chronic (4 weeks) RBJ, PBO+NIT, nitrate-free RBJ, and placebo supplementation via measurement of saliva and plasma nitrate/nitrite (NOx), plasma nitrite levels, and reactive hyperemia index (RHI). Results A significant decrease in the alpha diversity metric, Pileou's Evenness, was detected after chronic consumption of PBO+NIT (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P &lt; 0.05), while there was a trend for a decline following RBJ consumption (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P = 0.08). No significant differences in abundance of nitrate-reducing bacteria were observed after chronic supplementation, although abundance of the species Neisseria subflava was trending toward an increase in the RBJ group (10.8% at week 0 vs. 12.2% at week 4; P = 0.07). Plasma and saliva NOx increased from baseline and remained elevated for the 4-hour testing period after acute and chronic RBJ and PBO+NIT supplementation (all P &lt; 0.05), while plasma nitrite only peaked at 2 hours in the RBJ group after acute supplementation and was significantly higher than PBO+NIT group (P &lt; 0.01). RHI change from baseline to 4 hours was positively correlated with total abundance of nitrate-reducing species after chronic RBJ supplementation (r = 0.5; P = 0.05). Conclusions Acute and chronic RBJ and PBO+NIT supplementation increases NO metabolites and may alter the oral microbiota to favorably affect vascular endothelial function in middle-aged/older adults with overweight and obesity. Funding Sources NIFA, USDA.


2014 ◽  
Vol 307 (7) ◽  
pp. R920-R930 ◽  
Author(s):  
James Kelly ◽  
Anni Vanhatalo ◽  
Stephen J. Bailey ◽  
Lee J. Wylie ◽  
Christopher Tucker ◽  
...  

We investigated the effects of dietary nitrate (NO3−) supplementation on the concentration of plasma nitrite ([NO2−]), oxygen uptake (V̇o2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a double-blind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO3−-rich beetroot juice (8.4 mmol NO3; BR) or NO3−-depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO2−] was significantly elevated in H-BR and N-BR compared with H-PL ( P < 0.01) and N-PL ( P < 0.01). The rate of decline in plasma [NO2−] was greater during severe-intensity exercise in H-BR [−30 ± 22 nM/min, 95% confidence interval (CI); −44, −16] compared with H-PL (−7 ± 10 nM/min, 95% CI; −13, −1; P < 0.01) and in N-BR (−26 ± 19 nM/min, 95% CI; −38, −14) compared with N-PL (−1 ± 6 nM/min, 95% CI; −5, 2; P < 0.01). During moderate-intensity exercise, steady-state pulmonary V̇o2 was lower in H-BR (1.91 ± 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 ± 0.25 l/min, 95% CI; 1.93, 2.26; P = 0.02), and V̇o2 kinetics was faster in H-BR (τ: 24 ± 13 s, 95% CI; 15, 32) compared with H-PL (31 ± 11 s, 95% CI; 23, 38; P = 0.04). NO3− supplementation had no significant effect on V̇o2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO3− in hypoxia (H-PL: 197 ± 28; 95% CI; 173, 220 vs. H-BR: 214 ± 43 s, 95% CI; 177, 249; P = 0.04) but not normoxia. The metabolism of NO2− during exercise is altered by NO3− supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO3− supplementation enhances V̇o2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude.


2010 ◽  
Vol 109 (5) ◽  
pp. 1394-1403 ◽  
Author(s):  
Stephen J. Bailey ◽  
Paul G. Winyard ◽  
Anni Vanhatalo ◽  
Jamie R. Blackwell ◽  
Fred J. DiMenna ◽  
...  

It has recently been reported that dietary nitrate (NO3−) supplementation, which increases plasma nitrite (NO2−) concentration, a biomarker of nitric oxide (NO) availability, improves exercise efficiency and exercise tolerance in healthy humans. We hypothesized that dietary supplementation with l-arginine, the substrate for NO synthase (NOS), would elicit similar responses. In a double-blind, crossover study, nine healthy men (aged 19–38 yr) consumed 500 ml of a beverage containing 6 g of l-arginine (Arg) or a placebo beverage (PL) and completed a series of “step” moderate- and severe-intensity exercise bouts 1 h after ingestion of the beverage. Plasma NO2− concentration was significantly greater in the Arg than the PL group (331 ± 198 vs. 159 ± 102 nM, P < 0.05) and systolic blood pressure was significantly reduced (123 ± 3 vs. 131 ± 5 mmHg, P < 0.01). The steady-state O2 uptake (V̇o2) during moderate-intensity exercise was reduced by 7% in the Arg group (1.48 ± 0.12 vs. 1.59 ± 0.14 l/min, P < 0.05). During severe-intensity exercise, the V̇o2 slow component amplitude was reduced (0.58 ± 0.23 and 0.76 ± 0.29 l/min in Arg and PL, respectively, P < 0.05) and the time to exhaustion was extended (707 ± 232 and 562 ± 145 s in Arg and PL, respectively, P < 0.05) following consumption of Arg. In conclusion, similar to the effects of increased dietary NO3− intake, elevating NO bioavailability through dietary l-Arg supplementation reduced the O2 cost of moderate-intensity exercise and blunted the V̇o2 slow component and extended the time to exhaustion during severe-intensity exercise.


Nitric Oxide ◽  
2020 ◽  
Vol 99 ◽  
pp. 25-33 ◽  
Author(s):  
Stuart P. Cocksedge ◽  
Brynmor C. Breese ◽  
Paul T. Morgan ◽  
Leonardo Nogueira ◽  
Christopher Thompson ◽  
...  

2017 ◽  
Vol 312 (1) ◽  
pp. R13-R22 ◽  
Author(s):  
Daniel M. Hirai ◽  
Joel T. Zelt ◽  
Joshua H. Jones ◽  
Luiza G. Castanhas ◽  
Robert F. Bentley ◽  
...  

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.


Sign in / Sign up

Export Citation Format

Share Document