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Effects of dietary nitrate on respiratory physiology at high altitude: results from the Xtreme Alps study

Effects of dietary nitrate on respiratory physiology at high altitude: results from the Xtreme Alps study
Effects of dietary nitrate on respiratory physiology at high altitude: results from the Xtreme Alps study
Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate ‘placebo’ of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0mPa at SL, to 3.5/7.4mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (p=0.02). EBC nitrite also rose significantly with dietary nitrate (p=0.004), 1.7 to 5.1μM at SL and 1.6 to 6.3 μM at D5, and this rise correlated with increased levels of ENO (R=0.5, p<0.0001). However no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786µM to 333/5194µM at SL, to 85.6/641µM and 341/4553µM on D5. Salivary RXNO rose markedly with treatment at SL from 0.55µM to 5.70µM. At D5 placebo salivary RXNO had increased to 1.90µM whilst treatment RXNO decreased to 3.26µM. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.
nitrite, nitrate, altitude, nitric oxide, hypoxia, hypoxaemia
1089-8603
57-68
Cumpstey, Andrew F.
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Hennis, Philip J.
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Gilbert-kawai, Edward T.
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Fernandez, Bernadette O.
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Poudevigne, Matthieu
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Cobb, Alexandra
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Meale, Paula
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Mitchell, Kay
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Moyses, Helen
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Pöhnl, Helmut
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Mythen, Monty G.
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Grocott, Michael P.w.
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Feelisch, Martin
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Martin, Daniel S.
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Cumpstey, Andrew F.
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Hennis, Philip J.
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Gilbert-kawai, Edward T.
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Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Poudevigne, Matthieu
7522102d-91ef-4c8b-b2a1-4e92a7a818e6
Cobb, Alexandra
7e071e58-7ce9-46e9-b8b8-d201f71a9a02
Meale, Paula
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Mitchell, Kay
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Moyses, Helen
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Pöhnl, Helmut
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Mythen, Monty G.
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Grocott, Michael P.w.
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Feelisch, Martin
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Martin, Daniel S.
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Cumpstey, Andrew F., Hennis, Philip J., Gilbert-kawai, Edward T., Fernandez, Bernadette O., Poudevigne, Matthieu, Cobb, Alexandra, Meale, Paula, Mitchell, Kay, Moyses, Helen, Pöhnl, Helmut, Mythen, Monty G., Grocott, Michael P.w., Feelisch, Martin and Martin, Daniel S. (2017) Effects of dietary nitrate on respiratory physiology at high altitude: results from the Xtreme Alps study. Nitric Oxide, 71, 57-68. (doi:10.1016/j.niox.2017.10.005).

Record type: Article

Abstract

Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate ‘placebo’ of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0mPa at SL, to 3.5/7.4mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (p=0.02). EBC nitrite also rose significantly with dietary nitrate (p=0.004), 1.7 to 5.1μM at SL and 1.6 to 6.3 μM at D5, and this rise correlated with increased levels of ENO (R=0.5, p<0.0001). However no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786µM to 333/5194µM at SL, to 85.6/641µM and 341/4553µM on D5. Salivary RXNO rose markedly with treatment at SL from 0.55µM to 5.70µM. At D5 placebo salivary RXNO had increased to 1.90µM whilst treatment RXNO decreased to 3.26µM. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.

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Accepted/In Press date: 13 October 2017
e-pub ahead of print date: 17 October 2017
Published date: 1 December 2017
Keywords: nitrite, nitrate, altitude, nitric oxide, hypoxia, hypoxaemia

Identifiers

Local EPrints ID: 415000
URI: http://eprints.soton.ac.uk/id/eprint/415000
ISSN: 1089-8603
PURE UUID: 5700aff0-9fa0-476b-8438-027f5ffd2462
ORCID for Andrew F. Cumpstey: ORCID iD orcid.org/0000-0001-6257-207X
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Kay Mitchell: ORCID iD orcid.org/0000-0001-6393-8475
ORCID for Michael P.w. Grocott: ORCID iD orcid.org/0000-0002-9484-7581
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 20 Oct 2017 16:31
Last modified: 21 Nov 2024 03:05

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Contributors

Author: Andrew F. Cumpstey ORCID iD
Author: Philip J. Hennis
Author: Edward T. Gilbert-kawai
Author: Bernadette O. Fernandez ORCID iD
Author: Matthieu Poudevigne
Author: Alexandra Cobb
Author: Paula Meale
Author: Kay Mitchell ORCID iD
Author: Helen Moyses
Author: Helmut Pöhnl
Author: Monty G. Mythen
Author: Martin Feelisch ORCID iD
Author: Daniel S. Martin

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