Human skeletal muscle nitrate store: Influence of dietary nitrate supplementation and exercise
Open accessAbstract
Key points: Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions. We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise. In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high‐intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO. We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism. Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise‐induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4‐fold and ∼29‐fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19‐fold) and muscle (∼5‐fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise‐induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.
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TL;DR
Human skeletal muscle contains much higher baseline nitrate and nitrite concentrations than plasma, and a single dietary nitrate bolus substantially increases muscle nitrate. A high-intensity exercise bout reduced muscle nitrate only when the muscle nitrate store was elevated by prior nitrate ingestion, suggesting human muscle nitrate may contribute to local NO generation during exercise.
Key findings
- Baseline muscle nitrate was ~4-fold higher than plasma (226 ± 213 vs. 54 ± 27 nmol g⁻¹) and muscle nitrite was ~29-fold higher than plasma (5.7 ± 7.4 vs. 0.2 ± 0.2 nmol g⁻¹; both P < 0.01).
- A single 12.8 mmol (794 mg) dietary nitrate bolus increased plasma nitrate ~19-fold to 1082 ± 731 nmol g⁻¹ and muscle nitrate ~5-fold to 1139 ± 894 nmol g⁻¹ (P < 0.01); muscle nitrite increased ~3-fold to 14.2 ± 21.4 nmol g⁻¹ but was not statistically significant (P = 0.13).
- After nitrate ingestion, high-intensity exercise reduced muscle nitrate by ~39% (P < 0.05) and plasma nitrite by ~34% (P < 0.01), but no significant exercise-induced changes occurred in the placebo condition.
- Sialin, NOS1, XOR, and AO were expressed in human skeletal muscle, with substantial inter-individual variability; baseline muscle nitrate ranged from 30 to 1036 nmol g⁻¹ and the post-nitrate increase ranged from 247 to 2723 nmol g⁻¹.
Methods
- Thirteen healthy, recreationally active participants (8 males, 5 females) completed two experimental visits after a standardized low-nitrate diet; they ingested either nitrate-rich beetroot juice (12.8 mmol nitrate) or nitrate-depleted placebo, then rested 2 h before a high-intensity cycle step test to task failure.
- Blood and vastus lateralis muscle biopsies were collected at baseline, post-supplement, and post-exercise; nitrate/nitrite were measured by gas-phase chemiluminescence, and sialin, XOR, AO, and NOS1 expression by Western blot.
- Independent paired-sample Student’s t tests were used for key comparisons, with Pearson correlations for relationships; significance was accepted at P < 0.05.
Limitations
- The paper states that a full dataset (n = 13) was not available for all variables because blood or muscle samples were not always obtained, and that the muscle nitrite increase after nitrate ingestion was non-significant due to large inter-individual variability.
- The paper states that acute nitrate supplementation did not improve time to task failure (PLA: 396 ± 102 s vs. NIT: 389 ± 110 s), that the functional advantage of the muscle nitrate changes remains unclear, and that larger studies are needed; it also notes possible nitrate deficiency from the pre-visit low-nitrate diet and the shorter exercise duration compared with rodent studies.
- Evident from the text: the study is small, acute, and in young healthy recreationally active adults, with high inter-individual variability in nitrate storage and protein expression, limiting generalizability and causal inference.
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- Findingown data
Baseline nitrite concentration is approximately 29-fold higher in skeletal muscle than in plasma in young healthy humans.
“baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (~4-fold and ~29-fold, respectively)”
- Also stated in: § Baseline plasma and muscle nitrate and nitrite concentrations · plain
“Nitrate (226 ± 213 nmol g−1) and nitrite (5.7 ± 7.4 nmol g−1) concentrations in skeletal muscle were much higher than in plasma (nitrate: 54 ± 27 nmol g−1; nitrite: 0.2 ± 0.2 nmol g−1; both P < 0.01).”
Quote in the paperSubstantial claim - Also stated in: § Baseline plasma and muscle nitrate and nitrite concentrations · plain
- Findingown data
Baseline nitrate concentration is approximately 4-fold higher in skeletal muscle than in plasma in young healthy humans.
“We showed that the baseline concentration of nitrate was 4-fold higher in skeletal muscle than in plasma (Fig. 2).”
- Also stated in: § Baseline plasma and muscle nitrate and nitrite concentrations · plain
“Nitrate (226 ± 213 nmol g−1) and nitrite (5.7 ± 7.4 nmol g−1) concentrations in skeletal muscle were much higher than in plasma (nitrate: 54 ± 27 nmol g−1; nitrite: 0.2 ± 0.2 nmol g−1; both P < 0.01).”
Quote in the paperSubstantial claim - Also stated in: § Baseline plasma and muscle nitrate and nitrite concentrations · plain
- Findingown data
Consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated plasma nitrate concentration by approximately 19-fold in young healthy humans.
“Two hours after dietary nitrate consumption, the concentration of nitrate in plasma increased ~19-fold to 1082 ± 731 nmol g−1 (n = 11; Fig. 3A)”
- Also stated in: § Abstract · plain
“the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (~19-fold) and muscle (~5-fold)”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
After dietary nitrate ingestion, plasma nitrite concentration increased approximately 3-fold in young healthy humans.
“After dietary nitrate ingestion, the concentration of nitrite in plasma increased ~3-fold to 0.7 ± 0.6 nmol g−1, compared to baseline (P < 0.01; n = 11; Fig. 3C).”
Quote in the paperSubstantial claim - Findingown data
Consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated muscle nitrate concentration by approximately 5-fold in young healthy humans.
“the concentration of nitrate in muscle increased ~5-fold to 1139 ± 894 nmol g−1 (n = 13; Fig. 3B), compared to baseline (P < 0.01).”
- Also stated in: § Abstract · plain
“the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (~19-fold) and muscle (~5-fold)”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In the dietary nitrate condition, muscle nitrate concentration was reduced by approximately 39% over the course of a high-intensity exercise bout.
“Under these conditions, muscle nitrate concentration was reduced by ~39% (n = 11; P < 0.05; Fig. 4B)”
Quote in the paperSubstantial claim - Findingown data
Plasma nitrite concentration is not correlated with plasma nitrate concentration.
“but plasma nitrite concentration was not correlated with plasma nitrate concentration (r = −0.02; P > 0.05).”
Quote in the paperNot a substantial claim - Findingown data
In the dietary nitrate condition, plasma nitrite concentration was reduced by approximately 34% over the course of a high-intensity exercise bout.
“and plasma nitrite concentration was reduced by ~34% (n = 10; P < 0.01; Fig. 4C) over the course of the exercise bout.”
Quote in the paperNot a substantial claim - Findingown data
The expression of XOR and sialin, and to a lesser extent NOS1 and AO, varies substantially between individuals.
“However, the expression of XOR and sialin, and to a lesser extent, NOS1 and AO, appears to vary substantially between individuals.”
Quote in the paperNot a substantial claim - Findingown data
Sialin protein is expressed in human skeletal muscle tissue.
“As can be seen in Fig. 5, NOS1, XOR, AO and sialin were expressed in the skeletal muscle tissue of all participants.”
- Also stated in: § Abstract · boosted
“we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · boosted
- Findingown data
AO protein is expressed in human skeletal muscle tissue.
“As can be seen in Fig. 5, NOS1, XOR, AO and sialin were expressed in the skeletal muscle tissue of all participants.”
Quote in the paperSubstantial claim - Findingown data
Human skeletal muscle nitrite concentration is far higher than plasma nitrite concentration.
“Interestingly, we found that in humans nitrite is present in muscle at far higher concentrations than is observed in plasma (Fig. 2B).”
- Also stated in: § Conclusions · boosted
“We show for the first time in humans that baseline concentrations of both nitrate and nitrite are far greater in skeletal muscle than in plasma.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · boosted
- Findingown data
In the placebo condition, high-intensity exercise did not significantly influence plasma nitrate, plasma nitrite, muscle nitrate, or muscle nitrite concentrations.
“Under these conditions, the high-intensity exercise bout did not significantly influence plasma nitrate (n = 13) and nitrite (n = 13), or muscle nitrate (n = 10) and nitrite (n = 10) concentrations (all P > 0.05; Fig. 4).”
Quote in the paperSubstantial claim - Findingown data
Muscle nitrite concentration is positively correlated with muscle nitrate concentration.
“Muscle nitrite concentration was positively correlated with muscle nitrate concentration (r = 0.77; P < 0.01)”
Quote in the paperNot a substantial claim - Findingown data
NOS1 protein is expressed in human skeletal muscle tissue.
“As can be seen in Fig. 5, NOS1, XOR, AO and sialin were expressed in the skeletal muscle tissue of all participants.”
Quote in the paperSubstantial claim - Findingown data
XOR protein is expressed in human skeletal muscle tissue.
“As can be seen in Fig. 5, NOS1, XOR, AO and sialin were expressed in the skeletal muscle tissue of all participants.”
- Also stated in: § Introduction · plain
“The presence of XOR in human skeletal muscle (Hellsten-Westing, 1993) implies that this nitrate–nitrite pathway may be active and important in humans as well as in rats (Piknova et al. 2016b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hellsten-Westing, 1993
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- Also stated in: § Introduction · plain
- Findingown data
Acute dietary nitrate supplementation did not alter the time to task failure during short-duration (~6-7 min), high-intensity cycle exercise.
“In the present study, acute dietary nitrate supplementation did not alter the time to task failure during short-duration (~6–7 min), high-intensity cycle exercise.”
Quote in the paperSubstantial claim - Findingown data
The increase in muscle nitrate concentration after dietary nitrate consumption varies substantially between individuals, with a range of 247-2723 nmol g tissue−1.
“A further important finding from the present study is the substantial inter-individual difference in both baseline muscle nitrate concentration (range: 30–1036 nmol g tissue−1) and in the increase in muscle nitrate concentration after consumption of dietary nitrate (range: 247–2723 nmol g tissue−1).”
Quote in the paperSubstantial claim - Findingcitation
Dietary nitrate consumption significantly increases plasma nitrite.
“As reported previously (e.g. Wylie et al. 2013) and as shown in Fig. 3C, a significant increase in plasma nitrite occurs after the consumption of dietary nitrate, an effect that is mostly dependent on nitrate-to-nitrite reduction by commensal bacteria in the oral cavity (Govoni et al. 2008).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Wylie et al. 2013
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- cites Govoni et al. 2008
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- Findingown data
XOR is present in human skeletal muscle tissue.
“The presence of XOR and AO in human skeletal muscle tissue (Fig. 5) suggests that this pathway may also be functional in humans.”
Quote in the paperSubstantial claim - Findingown data
Exercise under basal conditions did not reduce muscle nitrate concentration.
“We found a reduction in muscle nitrate when the exercise bout was initiated after nitrate consumption and, therefore, in the presence of an increased muscle nitrate store (Fig. 4B), but not after exercise under basal conditions.”
Quote in the paperSubstantial claim - Findingown data
Exercise after nitrate consumption reduced muscle nitrate concentration.
“We found a reduction in muscle nitrate when the exercise bout was initiated after nitrate consumption and, therefore, in the presence of an increased muscle nitrate store (Fig. 4B), but not after exercise under basal conditions.”
- Also stated in: § Conclusions · plain
“We also report an exercise-induced reduction in muscle nitrate concentration following nitrate ingestion.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Findingown data
Dietary nitrate consumption significantly increased plasma nitrate concentration.
“Nitrate consumption significantly increased plasma nitrate (Fig. 3A) and muscle nitrate concentrations (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
Muscle nitrite concentration increased in all but two of the participants assessed after dietary nitrate consumption.
“Two hours after the consumption of dietary nitrate, we observed a 3-fold increase in muscle nitrite concentration. While this difference did not reach statistical significance, due to large variability between individuals, the concentration of muscle nitrite increased in all but two of the participants assessed (Fig. 3D).”
Quote in the paperSubstantial claim - Findingown data
Baseline muscle nitrate concentration varies substantially between individuals, with a range of 30-1036 nmol g tissue−1.
“A further important finding from the present study is the substantial inter-individual difference in both baseline muscle nitrate concentration (range: 30–1036 nmol g tissue−1) and in the increase in muscle nitrate concentration after consumption of dietary nitrate (range: 247–2723 nmol g tissue−1).”
Quote in the paperSubstantial claim - Findingown data
Dietary nitrate consumption significantly increased muscle nitrate concentration.
“Nitrate consumption significantly increased plasma nitrate (Fig. 3A) and muscle nitrate concentrations (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
Baseline muscle nitrate concentration is far greater than plasma nitrate concentration.
“We show for the first time in humans that baseline concentrations of both nitrate and nitrite are far greater in skeletal muscle than in plasma.”
- Also stated in: § Influence of nitrate ingestion on muscle nitrate and nitrite concentrations · hedged
“Both the muscle-to-blood nitrate gradient under basal conditions (Fig. 2), and the rise in muscle nitrate after dietary nitrate consumption (Fig. 3B), suggests that human skeletal muscle possesses active nitrate transport machinery.”
Quote in the paperSubstantial claim - Also stated in: § Influence of nitrate ingestion on muscle nitrate and nitrite concentrations · hedged
- Findingown data
Sialin is present in human skeletal muscle tissue.
“We report here that sialin is also present in human skeletal muscle tissue (Fig. 5), which suggests that it may be involved in skeletal muscle nitrate uptake.”
- Also stated in: § Conclusions · plain
“We also report that the active nitrate transporter sialin is present in human skeletal muscle and propose that this transporter may be responsible for the increase in muscle nitrate concentration observed following the consumption of dietary nitrate.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Findingown data
AO is present in human skeletal muscle tissue.
“The presence of XOR and AO in human skeletal muscle tissue (Fig. 5) suggests that this pathway may also be functional in humans.”
Quote in the paperSubstantial claim - Findingown data
There is a positive correlation between basal muscle nitrate and nitrite concentrations.
“the positive correlation between basal muscle nitrate and nitrite concentrations suggest that intramuscular nitrate reduction also contributes to this nitrite pool.”
Quote in the paperSubstantial claim - Interpretationown data
Human skeletal muscle nitrate stores are sensitive to dietary nitrate intake.
“Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise.”
- Also stated in: § Discussion · plain
“We show that nitrate and nitrite are present in human skeletal muscle at far higher concentrations than are observed in plasma, and that the concentration of nitrite and particularly nitrate increase after the consumption of dietary nitrate.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Premisecitation
The concentration of nitrate in skeletal muscle is far greater than in blood or other organs in rodents and humans.
“The concentration of nitrate in skeletal muscle has been found to be far greater than in blood or other organs in rodents (Piknova et al. 2015, 2016b) and humans (Nyakayiru et al. 2017).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Piknova et al. 2015, 2016b
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- cites Nyakayiru et al. 2017
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- Premisecitation
Rodent skeletal muscle tissue is capable of nitrate-to-nitrite reduction, catalysed predominantly by XOR.
“It was recently discovered that rodent skeletal muscle tissue is capable of nitrate-to-nitrite reduction, in a reaction catalysed predominantly by XOR (Piknova et al. 2015, 2016b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Piknova et al. 2015, 2016b
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- Premisecitation
Exercise-induced reductions in rodent skeletal muscle nitrate indicate that this pathway may be important for NO supply during exercise.
“Moreover, exercise-induced reductions in rodent skeletal muscle nitrate (and transient increases in nitrite) indicate that this pathway may be important for NO supply during exercise, a situation in which NOS function is likely impaired by the accompanying fall in pH and O2 availability (Lundberg et al. 2008; Black et al. 2017).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Lundberg et al. 2008
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- cites Black et al. 2017
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- Study design and conductown data
The time to task failure was similar in the placebo and dietary nitrate conditions.
“The time to task failure was similar in the placebo and dietary nitrate conditions (PLA: 396 ± 102 s vs. NIT: 389 ± 110 s; n = 12; P > 0.05)”
Quote in the paperNot a substantial claim - Interpretationreasoning
Intramuscular nitrate reduction also contributes to the muscle nitrite pool.
“However, the presence of XOR in human skeletal muscle (Fig. 5), the reduction in muscle nitrate during acute exercise (see below), and the positive correlation between basal muscle nitrate and nitrite concentrations suggest that intramuscular nitrate reduction also contributes to this nitrite pool.”
Quote in the paperSubstantial claim - Study design and conductown data
The V̇O2 reached at the end of the exercise bout was similar in the placebo and nitrate conditions.
“and the V˙O2 reached at the end of the exercise bout was also similar in the placebo (3.43 ± 0.63 L min−1) and nitrate (3.43 ± 0.63 L min−1; n = 12; P > 0.05) conditions.”
Quote in the paperNot a substantial claim - Premisecitation
Continuous NO generation is essential in resting and contracting skeletal muscle.
“Continuous NO generation is essential in resting and contracting skeletal muscle due to its role in mitochondrial respiration, glucose uptake, force production and functional hyperaemia (Stamler & Meissner, 2001; McConell et al. 2012).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Stamler & Meissner, 2001
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- cites McConell et al. 2012
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- Interpretationown data
Muscle nitrate is metabolized during exercise, at least when muscle nitrate concentration is elevated.
“These findings suggest that an active nitrate transport system is present in human skeletal muscle, and that muscle nitrate is metabolized during exercise, at least when muscle nitrate concentration is elevated.”
- Also stated in: § Discussion · hedged
“Further, we report that the concentration of nitrate in skeletal muscle tissue is reduced following acute exercise, suggesting that nitrate may contribute to local NO generation. However, in contrast with our previous finding in rats (Piknova et al. 2016b), this occurs only when the muscle nitrate store is elevated above baseline, i.e. following dietary nitrate consumption.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Piknova et al. 2016b
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- Also stated in: § Discussion · hedged
- Interpretationreasoning
Skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.
“Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.”
Quote in the paperSubstantial claim - Interpretationcitation
The muscle nitrite pool may be an important source of NO generation in human skeletal muscle, particularly in hypoxic and acidic conditions.
“Irrespective of the source, the presence of several nitrite–NO pathways in skeletal muscle involving, for example, deoxymyoglobin (Shiva et al. 2007), mitochondrial enzymes (Kozlov et al. 1999) and XOR (Piknova et al. 2015), suggests that this nitrite pool may be an important source of NO generation in human skeletal muscle, particularly in hypoxic and acidic conditions.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Shiva et al. 2007
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- cites Kozlov et al. 1999
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- cites Piknova et al. 2015
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- Interpretationcitation
The presence of XOR in human skeletal muscle implies that the nitrate-nitrite pathway may be active and important in humans as well as in rats.
“The presence of XOR in human skeletal muscle (Hellsten-Westing, 1993) implies that this nitrate–nitrite pathway may be active and important in humans as well as in rats (Piknova et al. 2016b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Hellsten-Westing, 1993
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- cites Piknova et al. 2016b
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- Interpretationreasoning
Active uptake of nitrate from the bloodstream is likely important for the human muscle nitrate reservoir.
“However, the increase in muscle nitrate observed after dietary nitrate consumption presented here (Fig. 3), and the presence of the active nitrate transporter, sialin (Fig. 5), suggests that active uptake of nitrate from the bloodstream is likely also important.”
Quote in the paperSubstantial claim - Interpretationown data
An active nitrate transport system is present in human skeletal muscle.
“These findings suggest that an active nitrate transport system is present in human skeletal muscle, and that muscle nitrate is metabolized during exercise, at least when muscle nitrate concentration is elevated.”
- Also stated in: § Discussion · hedged
“We confirm the presence of sialin, a known active nitrate/nitrite ion transporter (Qin et al. 2012), in human muscle homogenates, consistent with the existence of an operational active transport system in human skeletal muscle.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Qin et al. 2012
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- Also stated in: § Discussion · hedged
- Interpretationown data
Human skeletal muscle nitrate stores may contribute to NO generation during exercise.
“Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise.”
- Also stated in: § Discussion · hedged
“Further, we report that the concentration of nitrate in skeletal muscle tissue is reduced following acute exercise, suggesting that nitrate may contribute to local NO generation.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Premisecitation
A large portion of the basal nitrate reservoir in rodents is produced by NOS.
“Based on experiments with the NOS1 (neuronal NOS) knock-out mouse and NOS inhibition in rats, a large portion of the basal nitrate reservoir in rodents was found to be produced by NOS (Haque et al. 2013; Piknova et al. 2015).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Haque et al. 2013
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- cites Piknova et al. 2015
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- Premisecitation
The muscle nitrate reservoir is an important source of nitrite and NO via its reduction by tissue xanthine oxidoreductase (XOR).
“This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase.”
- Also stated in: § Introduction · plain
“It was recently discovered that rodent skeletal muscle tissue is capable of nitrate-to-nitrite reduction, in a reaction catalysed predominantly by XOR (Piknova et al. 2015, 2016b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Piknova et al. 2015, 2016b
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- Also stated in: § Introduction · plain
- Premisecitation
Positive effects on exercise performance are more often reported following longer-duration (≥3-7 days) dietary nitrate supplementation.
“The physiological and other factors that may influence the ergogenicity of nitrate supplementation are debated but it is clear that positive effects on exercise performance are more often reported following longer-duration (≥3–7 days) dietary supplementation (Jones et al. 2018).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jones et al. 2018
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- Premisecitation
There is a larger array of known nitrite-NO reduction pathways than nitrate-nitrite pathways in skeletal muscle.
“Indeed, there is a larger array of known nitrite–NO reduction pathways than nitrate–nitrite pathways in skeletal muscle (Kozlov et al. 1999; Shiva et al. 2007; van Faassen et al. 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Kozlov et al. 1999
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- cites Shiva et al. 2007
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- cites van Faassen et al. 2009
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- Interpretationreasoning
Baseline muscle nitrate concentration likely reflects the balance between nitrate transport into the muscle from the bloodstream, endogenous nitrate synthesis within the muscle, and nitrate reduction by XOR, AO or other mammalian nitrate reductases.
“Baseline muscle nitrate concentration likely reflects the balance between nitrate transport into the muscle from the bloodstream, endogenous nitrate synthesis within the muscle (i.e. oxidation of NOS-derived NO and nitrate production by NOS1) and nitrate reduction by XOR, AO or other mammalian nitrate reductases.”
Quote in the paperSubstantial claim - Interpretationreasoning
Skeletal muscle has the potential to play a role in the regulation of whole-body NO bioavailability.
“This suggests that skeletal muscle has the potential to play a role in the regulation of whole-body NO bioavailability.”
Quote in the paperSubstantial claim - Interpretationreasoning
Large inter-individual differences in sialin expression may mediate the variable increase in muscle nitrate concentration observed after nitrate consumption.
“Moreover, assuming that sialin is involved in muscle nitrate uptake, the large inter-individual differences in the expression of this protein (Fig. 5) may also be mediating the variable increase in muscle nitrate concentration observed after nitrate consumption (Fig. 3B).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: Sialin is involved in muscle nitrate uptake.
- Interpretationown data
The skeletal muscle of young and older adults effectively sequesters nitrate from the bloodstream.
“Together, these findings confirm that the skeletal muscle of young and older adults effectively sequesters nitrate from the bloodstream.”
Quote in the paperSubstantial claim - Interpretationown data
The muscle nitrate reduction pathway in humans may be particularly active when local nitrate availability is high.
“These findings differ from our previous study in rats, in which nitrate reduction was observed under non-supplemented conditions (Piknova et al. 2016b), and suggests that the muscle nitrate reduction pathway in humans may be particularly active when local nitrate availability is high.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Piknova et al. 2016b
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- Interpretationreasoning
Sialin may be responsible for the increase in muscle nitrate concentration observed following the consumption of dietary nitrate.
“We also report that the active nitrate transporter sialin is present in human skeletal muscle and propose that this transporter may be responsible for the increase in muscle nitrate concentration observed following the consumption of dietary nitrate.”
Quote in the paperSubstantial claim - Interpretationown data
The functional advantage of the increase in muscle nitrate concentration following dietary nitrate supplementation and of the reduction of muscle nitrate during exercise remains unclear.
“Nevertheless, on the basis of the results of the present study, in which there was no significant benefit to exercise performance, the functional advantage of the increase in muscle nitrate concentration following dietary nitrate supplementation and of the reduction of muscle nitrate during exercise, remains unclear.”
Quote in the paperSubstantial claim - Interpretationreasoning
Human skeletal muscle possesses active nitrate transport machinery.
“Both the muscle-to-blood nitrate gradient under basal conditions (Fig. 2), and the rise in muscle nitrate after dietary nitrate consumption (Fig. 3B), suggests that human skeletal muscle possesses active nitrate transport machinery.”
Quote in the paperSubstantial claim - Interpretationreasoning
Uptake of plasma nitrite by skeletal muscle results in an increase in muscle nitrite after dietary nitrate consumption.
“Uptake of this nitrite by skeletal muscle results in an increase in muscle nitrite after dietary nitrate consumption (Fig. 3D).”
Quote in the paperSubstantial claim - Premisecitation
During skeletal muscle contraction, an increase in NO supply occurs to support the elevated rate of mitochondrial respiration, glucose uptake and other processes, including functional hyperaemia.
“During skeletal muscle contraction, an increase in NO supply occurs to support the elevated rate of mitochondrial respiration, glucose uptake and other processes, including functional hyperaemia (Stamler & Meissner, 2001).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Stamler & Meissner, 2001
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- Interpretationreasoning
Improvements in skeletal muscle contractile force or fatigue resistance following dietary nitrate consumption are mediated, at least in part, by increased muscle nitrite concentration and NO bioavailability.
“This supports the assumption that improvements in skeletal muscle contractile force or fatigue resistance following dietary nitrate consumption (Bailey et al. 2010; Fulford et al. 2013; Haider & Folland, 2014; Coggan et al. 2015; Coggan & Peterson, 2018) are mediated, at least in part, by increased muscle nitrite concentration and NO bioavailability.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Bailey et al. 2010
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- cites Fulford et al. 2013
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- cites Haider & Folland, 2014
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- Interpretationreasoning
At least part of the large inter-individual variability in baseline muscle nitrate concentration may be related to the variable expression of NOS1, XOR, AO and sialin in muscle.
“It is therefore possible that at least part of the large inter-individual variability in baseline muscle nitrate concentration is related to the variable expression of NOS1, XOR, AO and sialin in muscle.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Sialin may be involved in skeletal muscle nitrate uptake.
“We report here that sialin is also present in human skeletal muscle tissue (Fig. 5), which suggests that it may be involved in skeletal muscle nitrate uptake.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The nitrate reduction pathway may also be functional in humans.
“The presence of XOR and AO in human skeletal muscle tissue (Fig. 5) suggests that this pathway may also be functional in humans.”
Quote in the paperSubstantial claim - Premisecitation
The increase in plasma nitrite after dietary nitrate is mostly dependent on nitrate-to-nitrite reduction by commensal bacteria in the oral cavity.
“As reported previously (e.g. Wylie et al. 2013) and as shown in Fig. 3C, a significant increase in plasma nitrite occurs after the consumption of dietary nitrate, an effect that is mostly dependent on nitrate-to-nitrite reduction by commensal bacteria in the oral cavity (Govoni et al. 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govoni et al. 2008
Not checked in the free run.
- Interpretationcitation
Skeletal muscle may act as a nitrate and nitrite reservoir, supporting whole-body NO homeostasis via diffusion-driven distribution of these ions into the bloodstream.
“Although further work is required, these findings are consistent with the hypothesis that skeletal muscle may act as a nitrate and nitrite ‘reservoir’, supporting whole body NO homeostasis via diffusion-driven distribution of these ions into the bloodstream (Piknova et al. 2015, 2016b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Piknova et al. 2015
Not checked in the free run.
- cites Piknova et al. 2016b
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- Interpretationown data
Human skeletal muscle NO generation during contraction may be supported by the reduction of local nitrate stores.
“Although exercise performance was not enhanced, this finding provides the first indication that, in these circumstances, human skeletal muscle NO generation during contraction may be supported by the reduction of local nitrate stores.”
Quote in the paperSubstantial claim
- May combine two claims. 16
- Classified as probably not a substantial claim. 17
May combine two claims.
Findingown dataAfter dietary nitrate ingestion, muscle nitrite concentration increased approximately 3-fold but the difference was not statistically significant.
“Nitrite concentration in muscle also increased ~3-fold to 14.2 ± 21.4 nmol g−1, although this difference was not statistically significant (P = 0.13; n = 13; Fig. 3D).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataPlacebo supplementation did not alter plasma nitrate, plasma nitrite, muscle nitrate, or muscle nitrite concentrations.
“As expected, the consumption of a placebo supplement did not alter plasma nitrate (n = 13) and nitrite (n = 13), or muscle nitrate (n = 11) and nitrite (n = 11) concentrations (all P > 0.05; Fig. 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the dietary nitrate condition, plasma nitrate and muscle nitrite concentrations were not influenced by the exercise bout.
“Plasma nitrate (n = 10) and muscle nitrite (n = 11) concentrations were not influenced by the exercise bout (both P > 0.05; Fig. 4A and D).”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationHuman skeletal muscle nitrite concentration is 5.7 nmol g tissue−1, consistent with rat skeletal muscle nitrite concentration of 5 nmol g tissue−1.
“The concentration of nitrite measured in human skeletal muscle (5.7 nmol g tissue−1) is consistent with that observed in the skeletal muscle of rats (5 nmol g tissue−1; Gilliard et al. 2018).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gilliard et al. 2018
Not checked in the free run.
May combine two claims.
Findingown dataTwo hours after dietary nitrate consumption, muscle nitrite concentration increased 3-fold, but this difference did not reach statistical significance.
“Two hours after the consumption of dietary nitrate, we observed a 3-fold increase in muscle nitrite concentration. While this difference did not reach statistical significance, due to large variability between individuals, the concentration of muscle nitrite increased in all but two of the participants assessed (Fig. 3D).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe exercise-induced lowering of muscle nitrate after nitrate consumption occurred alongside a non-significant ~40% decline in muscle nitrite.
“Conversely, in the present study, the exercise-induced lowering of muscle nitrate after nitrate consumption occurred alongside a non-significant ~40% decline in muscle nitrite.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA full dataset (n = 13) was not available for all variables due to failure to obtain a sample at a certain time point.
“A full dataset (n = 13) was not available for all variables due to the failure to obtain a sample (i.e. blood or muscle) at a certain time point.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAcute oral treatment with nitrate restores sympatholysis and improves post-exercise hyperaemia in patients with Becker muscular dystrophy.
“Acute oral treatment with nitrate, as a precursor of NO, restores sympatholysis and improves post-exercise hyperaemia in patients with Becker muscular dystrophy (Nelson et al. 2015; for review see Dombernowsky et al. 2018).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Nelson et al. 2015
Not checked in the free run.
- cites Dombernowsky et al. 2018
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSialin is a nitrate transporter known to concentrate nitrate from the blood into salivary glands.
“sialin, a nitrate transporter known to concentrate nitrate from the blood into salivary glands (Qin et al. 2012)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Qin et al. 2012
Not checked in the free run.
May combine two claims.
InterpretationreasoningBoth on-site oxidation of excess NOS-derived NO and active uptake of nitrite from the bloodstream likely contribute to the muscle nitrite pool.
“Both on-site oxidation of excess NOS-derived NO and active uptake of nitrite from the bloodstream likely contribute to this nitrite pool.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationOxymyoglobin-driven oxidation of excess NO produced by NOS1 and direct production of nitrate from NOS via its futile cycle contribute to the human muscle nitrate reservoir.
“It is likely that oxymyoglobin-driven oxidation of excess NO produced by this enzyme (and to a lesser extent, endothelial NOS (NOS3); J.W. Park, unpublished observations; Möller & Sylvén, 1981; Sylvén et al. 1984), and the direct production of nitrate from NOS via its ‘futile’ cycle (Stuehr et al. 2004; Li & Poulos, 2005; Tejero et al. 2009) contribute to this human muscle nitrate reservoir.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Stuehr et al. 2004
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- cites Li & Poulos, 2005
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- cites Tejero et al. 2009
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May combine two claims.
PremisecitationThe nitrate store is significantly elevated after the consumption of dietary nitrate in rodents and in diabetic older humans.
“However, it is also clear that the nitrate store is significantly elevated after the consumption of dietary nitrate, in both rodents (Gilliard et al. 2018) and in diabetic older humans (Nyakayiru et al. 2017).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Gilliard et al. 2018
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- cites Nyakayiru et al. 2017
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May combine two claims.
PremisecitationRodent skeletal muscle contains a large store of nitrate that can be augmented by dietary nitrate.
“Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate.”
- Also stated in: § Introduction · plain
“The concentration of nitrate in skeletal muscle has been found to be far greater than in blood or other organs in rodents (Piknova et al. 2015, 2016b) and humans (Nyakayiru et al. 2017).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Piknova et al. 2015, 2016b
Not checked in the free run.
- cites Nyakayiru et al. 2017
Not checked in the free run.
- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenOne participant did not reach the criteria for a maximal effort on one of the experimental trials and so these data were not included in the analyses related to the exercise bout.
“One participant did not reach the criteria for a maximal effort on one of the experimental trials and so these data were not included in the analyses related to the exercise bout.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCLC1 is an isoform present exclusively in skeletal muscle.
“It is also important to note that other transport systems capable of nitrate transport, such as chloride anion transporter 1 (CLC1), an isoform present exclusively in the skeletal muscle (Zifarelli & Pusch, 2009), may also be involved in active skeletal muscle nitrate uptake.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zifarelli & Pusch, 2009
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
InterpretationreasoningThe apparent contrast with rats may be explained by the high variability in the level of necessary enzymes in humans and the fact that, contrary to rodents, humans individualize their diets.
“The apparent contrast with rats may be explained by the high variability in the level of necessary enzymes in humans and the fact that, contrary to rodents, humans individualize their diets.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSialin is an active nitrate transporter responsible for concentrating nitrate from blood into salivary glands in humans.
“Sialin is an active nitrate transporter, and is known to be responsible for concentrating nitrate from blood into salivary glands in humans (Qin et al. 2012), an important first step for the conversion of nitrate to nitrite in the oral cavity (Lundberg et al. 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Qin et al. 2012
Not checked in the free run.
- cites Lundberg et al. 2008
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Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe participants in the present study may have been nitrate deficient upon arrival at the laboratory due to the prescribed low-nitrate diet in the 24 h preceding each testing visit.
“Moreover, it is possible that the participants in the present study were nitrate deficient upon arrival at the laboratory due to the prescribed low-nitrate diet in the 24 h preceding each testing visit.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDiet history influences the ability of skeletal muscle to store and possibly use nitrate, at least in rodents.
“This is likely important given that diet history influences the ability of skeletal muscle to store and possibly use nitrate, at least in rodents (Gilliard et al. 2018).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gilliard et al. 2018
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationOther transport systems such as CLC1 may also be involved in active skeletal muscle nitrate uptake.
“It is also important to note that other transport systems capable of nitrate transport, such as chloride anion transporter 1 (CLC1), an isoform present exclusively in the skeletal muscle (Zifarelli & Pusch, 2009), may also be involved in active skeletal muscle nitrate uptake.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zifarelli & Pusch, 2009
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe higher exercise intensity administered in the present study, compared to that in rodents, would likely have resulted in relatively greater muscle acidosis and hypoxia, further augmenting nitrite-to-NO reduction.
“Moreover, the higher exercise intensity administered in the present study, compared to that in rodents (Piknova et al. 2016b), would likely have resulted in relatively greater muscle acidosis and hypoxia, further augmenting nitrite-to-NO reduction.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Piknova et al. 2016b
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn rodents, a reduction in muscle nitrate during exercise was accompanied by a transient increase in muscle nitrite.
“In rodents, a reduction in muscle nitrate during exercise was accompanied by a transient increase in muscle nitrite (Piknova et al. 2016b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Piknova et al. 2016b
Not checked in the free run.
May combine two claims.
PremisecitationIn vitro experiments have revealed the presence of nitrate-to-nitrite and nitrite-to-NO reduction in rodent skeletal muscle homogenates, a process mediated principally by the mammalian nitrate reductase XOR, and facilitated by contraction-induced hypoxia and acidosis.
“Consistent with this hypothesis, in vitro experiments have revealed the presence of nitrate-to-nitrite and nitrite-to-NO reduction in rodent skeletal muscle homogenates, a process mediated (principally) by the mammalian nitrate reductase XOR, and facilitated by contraction-induced hypoxia and acidosis (Piknova et al. 2015, 2016b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Piknova et al. 2015
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- cites Piknova et al. 2016b
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationQin et al. (2012) reported low levels of sialin in the skeletal muscle of miniature pigs.
“Qin et al. (2012) reported the presence of low levels (relative to salivary gland, liver and brain) of sialin in the skeletal muscle of miniature pigs.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Qin et al. 2012
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone givenOther factors likely contribute to the variable increase in muscle nitrate after nitrate consumption, including dietary nitrate intake, physical activity levels, muscle fibre type and capillarization.
“However, it is likely that other factors also contribute, including dietary nitrate intake, physical activity levels, muscle fibre type and capillarization.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe observed increase in plasma and muscle nitrate is in line with previous findings.
“The observed increase of plasma and muscle nitrate is in line with previous findings from our group (Bailey et al. 2010; Wylie et al. 2013) and others (e.g. Nyakayiru et al. 2017).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Bailey et al. 2010
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- cites Wylie et al. 2013
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- cites Nyakayiru et al. 2017
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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Study design and conductnone givenVariability in exercise performance may be increased when invasive experimental techniques, particularly muscle biopsy procedures, are employed.
“It should also be acknowledged that variability in exercise performance may be increased when invasive experimental techniques, particularly muscle biopsy procedures, are employed.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationAcute exercise in rodents causes a significant decline in muscle nitrate and a transient increase in muscle nitrite.
“Recent observations that acute exercise in rodents causes a significant decline in muscle nitrate and a transient increase in muscle nitrite have raised the possibility that nitrate stored in skeletal muscle may be a significant source of NO (via a nitrite intermediate) during exercise.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe shorter exercise duration may have limited muscle nitrate reduction under basal conditions to an undetectable level.
“It is also possible that the shorter exercise duration (6.5 min in the present study compared to 1 h in the rodent study; Piknova et al. 2016b) limited muscle nitrate reduction under basal conditions to an undetectable level.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Piknova et al. 2016b
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAcute nitrate supplementation has been reported to be ergogenic in some but not all previous studies using a similar design.
“Acute nitrate supplementation has been reported to be ergogenic in some (e.g. Lansley et al. 2011; Shannon et al. 2017) but not all (e.g. Kelly et al. 2014) previous studies using a similar design.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Lansley et al. 2011
Not checked in the free run.
- cites Shannon et al. 2017
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- cites Kelly et al. 2014
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The authors state this as an assumption.
Sialin is involved in muscle nitrate uptake.
“Moreover, assuming that sialin is involved in muscle nitrate uptake, the large inter-individual differences in the expression of this protein (Fig. 5) may also be mediating the variable increase in muscle nitrate concentration observed after nitrate consumption (Fig. 3B).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle and plasma.
“Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle [88,89,90,91] and plasma [53,64,92], and are associated with positive physiological effects [41,64,74,93] that facilitate a greater capacity for muscular work [51,53,59] and/or improved muscle contractile efficiency (i.e., a lower high-energy phosphate cost of force production) [51,94].”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [91]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Statistical comparisons are described as both paired and independent t tests
MajorThe methods call the comparisons paired-sample t tests, then say the same baseline-to-post-supplement comparisons used independent t tests. Paired- and independent-sample t tests are different analyses, so the reported method is unclear.
“To maximize the available data for each key comparison, independent paired-sample Student’s t tests were employed.”
“differences between baseline and post-supplement nitrate and nitrite concentrations in plasma and muscle within the PLA and NIT arms of this study were assessed using independent Student’s t tests.”
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- Authors
- Wylie, L. J., Park, J. W., Vanhatalo, A., Kadach, S., Black, M. I., Stoyanov, Z., Schechter, A. N., Jones, A. M., & Piknova, B.
- Affiliations
- University of Exeter (GB)
- National Institutes of Health (US)
- Corresponding author
- Jones, Andrew M.
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2019-09
- Volume
- 597
- Issue
- 23
- Pages
- 5565-5576
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC9358602
- OpenAlex
- W2966325684
- Cited by
- 116
- References
- 53
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 17 · 2023: 16 · 2022: 17 · 2021: 16 · 2020: 19 · 2019: 6
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Physiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (Z99 DK999999)
- Biotechnology and Biological Sciences Research Council (BB/S020632/1)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitrate supplementation, nitric oxide, nitrite, sialin, xanthine oxidoreductase, high-intensity exercise, nitrate transport, nitrate metabolism, plasma nitrate
- MeSH terms
- Adolescent, Adult, Female, Humans, Lung, Male, Nitrates, Nitrites, Oxygen Consumption, Xanthine Dehydrogenase, Exercise, Muscle, Skeletal, Dietary Supplements, Organic Anion Transporters, Symporters, Young Adult
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