Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia

Non‐Technical Summary  Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high‐intensity exercise tolerance in healthy adults inhal...

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Published inThe Journal of physiology Vol. 589; no. 22; pp. 5517 - 5528
Main Authors Vanhatalo, Anni, Fulford, Jonathan, Bailey, Stephen J., Blackwell, James R., Winyard, Paul G., Jones, Andrew M.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.11.2011
Wiley Subscription Services, Inc
Blackwell Science Inc
Subjects
Adult
Beta vulgaris
Blood Pressure
Cross-Over Studies
Dietary Supplements
Double-Blind Method
Exercise Test
Exercise Tolerance - drug effects
Female
Humans
Hypoxia - blood
Hypoxia - drug therapy
Hypoxia - physiopathology
Integrative
Male
Muscle, Skeletal - drug effects
Muscle, Skeletal - physiopathology
Nitrates - pharmacology
Nitrites - blood
Plant Extracts - pharmacology
Plant Extracts - therapeutic use
Plant Roots - chemistry
Young Adult
Online AccessGet full text
ISSN0022-3751
1469-7793
1469-7793
DOI10.1113/jphysiol.2011.216341

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Abstract Non‐Technical Summary  Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high‐intensity exercise tolerance in healthy adults inhaling air containing 14.5% O2. In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders.   Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double‐blind, randomised crossover study, nine healthy subjects completed knee‐extension exercise to the limit of tolerance (Tlim), once in normoxia (20.9% O2; CON) and twice in hypoxia (14.5% O2). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate‐rich beetroot juice (9.3 mmol nitrate; H‐BR) or 0.75 L of nitrate‐depleted beetroot juice as a placebo (0.006 mmol nitrate; H‐PL). Muscle metabolism was assessed using calibrated 31P‐MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). Tlim was reduced in H‐PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H‐BR (477 ± 200 s). The muscle [PCr], [Pi] and pH changed at a faster rate in H‐PL compared to CON and H‐BR. The [PCr] recovery time constant was greater (P < 0.01) in H‐PL (29 ± 5 s) compared to CON (23 ± 5 s) and H‐BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate–nitrite–NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
AbstractList Non‐Technical Summary  Reduced atmospheric O 2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high‐intensity exercise tolerance in healthy adults inhaling air containing 14.5% O 2 . In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O 2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O 2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders. Abstract  Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double‐blind, randomised crossover study, nine healthy subjects completed knee‐extension exercise to the limit of tolerance (T lim ), once in normoxia (20.9% O 2 ; CON) and twice in hypoxia (14.5% O 2 ). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate‐rich beetroot juice (9.3 mmol nitrate; H‐BR) or 0.75 L of nitrate‐depleted beetroot juice as a placebo (0.006 mmol nitrate; H‐PL). Muscle metabolism was assessed using calibrated 31 P‐MRS. Plasma [nitrite] was elevated ( P < 0.01) following BR (194 ± 51 n m ) compared to PL (129 ± 23 n m ) and CON (142 ± 37 nM). T lim was reduced in H‐PL compared to CON (393 ± 169 vs . 471 ± 200 s; P < 0.05) but was not different between CON and H‐BR (477 ± 200 s). The muscle [PCr], [P i ] and pH changed at a faster rate in H‐PL compared to CON and H‐BR. The [PCr] recovery time constant was greater ( P < 0.01) in H‐PL (29 ± 5 s) compared to CON (23 ± 5 s) and H‐BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate–nitrite–NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T(lim)), once in normoxia (20.9% O(2); CON) and twice in hypoxia (14.5% O(2)). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated (31)P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). T(lim) was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P(i)] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Non-Technical Summary Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high-intensity exercise tolerance in healthy adults inhaling air containing 14.5% O2. In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders. Abstract Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (Tlim), once in normoxia (20.9% O2; CON) and twice in hypoxia (14.5% O2). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated 31P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 +/- 51 nm) compared to PL (129 +/- 23 nm) and CON (142 +/- 37 nM). Tlim was reduced in H-PL compared to CON (393 +/- 169 vs. 471 +/- 200 s; P < 0.05) but was not different between CON and H-BR (477 +/- 200 s). The muscle [PCr], [Pi] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 +/- 5 s) compared to CON (23 +/- 5 s) and H-BR (24 +/- 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Non‐Technical Summary  Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high‐intensity exercise tolerance in healthy adults inhaling air containing 14.5% O2. In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders.   Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double‐blind, randomised crossover study, nine healthy subjects completed knee‐extension exercise to the limit of tolerance (Tlim), once in normoxia (20.9% O2; CON) and twice in hypoxia (14.5% O2). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate‐rich beetroot juice (9.3 mmol nitrate; H‐BR) or 0.75 L of nitrate‐depleted beetroot juice as a placebo (0.006 mmol nitrate; H‐PL). Muscle metabolism was assessed using calibrated 31P‐MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). Tlim was reduced in H‐PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H‐BR (477 ± 200 s). The muscle [PCr], [Pi] and pH changed at a faster rate in H‐PL compared to CON and H‐BR. The [PCr] recovery time constant was greater (P < 0.01) in H‐PL (29 ± 5 s) compared to CON (23 ± 5 s) and H‐BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate–nitrite–NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T(lim)), once in normoxia (20.9% O(2); CON) and twice in hypoxia (14.5% O(2)). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated (31)P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). T(lim) was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P(i)] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (T(lim)), once in normoxia (20.9% O(2); CON) and twice in hypoxia (14.5% O(2)). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated (31)P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). T(lim) was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [P(i)] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Non-Technical Summary Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary supplementation with inorganic nitrate reduces markers of muscle fatigue and improves high-intensity exercise tolerance in healthy adults inhaling air containing 14.5% O2. In the body, nitrate can be converted to nitrite and nitric oxide. These molecules can improve muscle efficiency and also dilate blood vessels allowing more O2 to be delivered to active muscle. These results suggest that dietary nitrate could be beneficial during exercise at moderate to high altitude and in conditions where O2 delivery to muscle is reduced such as in pulmonary, cardiovascular and sleep disorders. Abstract Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation (which increases plasma [nitrite] and thus NO bioavailability) would ameliorate the adverse effects of hypoxia on muscle metabolism and oxidative function. In a double-blind, randomised crossover study, nine healthy subjects completed knee-extension exercise to the limit of tolerance (Tlim), once in normoxia (20.9% O2; CON) and twice in hypoxia (14.5% O2). During 24 h prior to the hypoxia trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice as a placebo (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed using calibrated 31P-MRS. Plasma [nitrite] was elevated (P < 0.01) following BR (194 ± 51 nm) compared to PL (129 ± 23 nm) and CON (142 ± 37 nM). Tlim was reduced in H-PL compared to CON (393 ± 169 vs. 471 ± 200 s; P < 0.05) but was not different between CON and H-BR (477 ± 200 s). The muscle [PCr], [Pi] and pH changed at a faster rate in H-PL compared to CON and H-BR. The [PCr] recovery time constant was greater (P < 0.01) in H-PL (29 ± 5 s) compared to CON (23 ± 5 s) and H-BR (24 ± 5 s). Nitrate supplementation reduced muscle metabolic perturbation during exercise in hypoxia and restored exercise tolerance and oxidative function to values observed in normoxia. The results suggest that augmenting the nitrate-nitrite-NO pathway may have important therapeutic applications for improving muscle energetics and functional capacity in hypoxia.
Author Bailey, Stephen J.
Blackwell, James R.
Fulford, Jonathan
Winyard, Paul G.
Jones, Andrew M.
Vanhatalo, Anni
Author_xml – sequence: 1
  givenname: Anni
  surname: Vanhatalo
  fullname: Vanhatalo, Anni
– sequence: 2
  givenname: Jonathan
  surname: Fulford
  fullname: Fulford, Jonathan
– sequence: 3
  givenname: Stephen J.
  surname: Bailey
  fullname: Bailey, Stephen J.
– sequence: 4
  givenname: James R.
  surname: Blackwell
  fullname: Blackwell, James R.
– sequence: 5
  givenname: Paul G.
  surname: Winyard
  fullname: Winyard, Paul G.
– sequence: 6
  givenname: Andrew M.
  surname: Jones
  fullname: Jones, Andrew M.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21911616$$D View this record in MEDLINE/PubMed
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Snippet Non‐Technical Summary  Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary...
Non‐Technical Summary  Reduced atmospheric O 2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary...
Exercise in hypoxia is associated with reduced muscle oxidative function and impaired exercise tolerance. We hypothesised that dietary nitrate supplementation...
Non-Technical Summary Reduced atmospheric O2 availability (hypoxia) impairs muscle oxidative energy production and exercise tolerance. We show that dietary...
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pubmed
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wiley
SourceType Open Access Repository
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StartPage 5517
SubjectTerms Adult
Beta vulgaris
Blood Pressure
Cross-Over Studies
Dietary Supplements
Double-Blind Method
Exercise Test
Exercise Tolerance - drug effects
Female
Humans
Hypoxia - blood
Hypoxia - drug therapy
Hypoxia - physiopathology
Integrative
Male
Muscle, Skeletal - drug effects
Muscle, Skeletal - physiopathology
Nitrates - pharmacology
Nitrites - blood
Plant Extracts - pharmacology
Plant Extracts - therapeutic use
Plant Roots - chemistry
Young Adult
Title Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia
URI https://onlinelibrary.wiley.com/doi/abs/10.1113%2Fjphysiol.2011.216341
https://www.ncbi.nlm.nih.gov/pubmed/21911616
https://www.proquest.com/docview/1545331110
https://www.proquest.com/docview/1837324710
https://www.proquest.com/docview/905668980
https://pubmed.ncbi.nlm.nih.gov/PMC3240888
Volume 589
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