The University of Southampton
University of Southampton Institutional Repository

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.
050a389c-f550-4453-a80a-f1a6e57db923
Hennis, Philip J.
b3563308-2f8e-49fb-a73f-c5afcc177ffe
Gilbert-kawai, Edward T.
1b96b8d0-3068-453a-89fc-6bc87cfbdba5
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Poudevigne, Matthieu
7522102d-91ef-4c8b-b2a1-4e92a7a818e6
Cobb, Alexandra
7e071e58-7ce9-46e9-b8b8-d201f71a9a02
Meale, Paula
92c84a2a-1392-4f4b-bbbd-8cb8009b553f
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Moyses, Helen
56434d9c-870f-4539-a66a-c791add44f67
Pöhnl, Helmut
c8eac2c4-c1fd-42e2-be10-4278862baefb
Mythen, Monty G.
266ffcca-f8dd-49b4-abe4-0ffb035e2b35
Grocott, Michael P.w.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Martin, Daniel S.
3e441b48-9221-4308-8ae6-49cbde20753f
Cumpstey, Andrew F.
050a389c-f550-4453-a80a-f1a6e57db923
Hennis, Philip J.
b3563308-2f8e-49fb-a73f-c5afcc177ffe
Gilbert-kawai, Edward T.
1b96b8d0-3068-453a-89fc-6bc87cfbdba5
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Poudevigne, Matthieu
7522102d-91ef-4c8b-b2a1-4e92a7a818e6
Cobb, Alexandra
7e071e58-7ce9-46e9-b8b8-d201f71a9a02
Meale, Paula
92c84a2a-1392-4f4b-bbbd-8cb8009b553f
Mitchell, Kay
f57f07cd-0e3a-48b2-a871-c436eec325ae
Moyses, Helen
56434d9c-870f-4539-a66a-c791add44f67
Pöhnl, Helmut
c8eac2c4-c1fd-42e2-be10-4278862baefb
Mythen, Monty G.
266ffcca-f8dd-49b4-abe4-0ffb035e2b35
Grocott, Michael P.w.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Martin, Daniel S.
3e441b48-9221-4308-8ae6-49cbde20753f

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.

Text
1-s2.0-S1089860317301672-main - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (1MB)

More information

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: https://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

Catalogue record

Date deposited: 20 Oct 2017 16:31
Last modified: 10 Dec 2019 01:40

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×