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Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude

Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude
Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude
The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients.
critical care, exercise, high altitude, hypoxaemia, hypoxia, microcirculation, nitric oxide
1551-7144
450-459
Martin, Daniel S.
f60d19f8-d4a0-44e2-b9b5-e6f18de00cd7
Gilbert-Kawai, Edward T.
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Meale, Paula M.
92c84a2a-1392-4f4b-bbbd-8cb8009b553f
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Cobb, Alexandra
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Khosravi, Maryam
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Mitchell, Kay
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Grocott, Michael P.W.
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Levett, Denny Z.H.
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Mythen, Michael G.
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Feelisch, Martin
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Martin, Daniel S.
f60d19f8-d4a0-44e2-b9b5-e6f18de00cd7
Gilbert-Kawai, Edward T.
1b96b8d0-3068-453a-89fc-6bc87cfbdba5
Meale, Paula M.
92c84a2a-1392-4f4b-bbbd-8cb8009b553f
Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Cobb, Alexandra
7e071e58-7ce9-46e9-b8b8-d201f71a9a02
Khosravi, Maryam
6fd48231-6c18-45ea-9132-784e2cae17cb
Mitchell, Kay
ab96393c-c922-4125-b3f8-2ad8a6e72289
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Levett, Denny Z.H.
4b33b751-32be-4fa3-aaf7-b62e62f08de8
Mythen, Michael G.
940f5be7-e5bc-4a90-94aa-09fdc658caad
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Martin, Daniel S., Gilbert-Kawai, Edward T., Meale, Paula M., Fernandez, Bernadette O., Cobb, Alexandra, Khosravi, Maryam, Mitchell, Kay, Grocott, Michael P.W., Levett, Denny Z.H., Mythen, Michael G. and Feelisch, Martin (2013) Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study of the effects of dietary nitrate supplementation on acclimatisation to high altitude Contemporary Clinical Trials, 36, (2), pp. 450-459. (doi:10.1016/j.cct.2013.09.002). (PMID:24028941).

Record type: Article

Abstract

The study of healthy human volunteers ascending to high altitude provides a robust model of the complex physiological interplay that emulates human adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may play an important role in both adaptation to high altitude and response to hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite concentrations can be augmented by dietary supplementation and this is associated with improved exercise performance and mitochondrial efficiency. We hypothesised that the administration of a dietary substance (beetroot juice) rich in nitrate would improve oxygen efficiency during exercise at high altitude by enhancing tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate supplementation would lead to measurable increases in NO bioactivity throughout the body. This methodological manuscript describes the design and conduct of the 'Xtreme Alps' expedition, a double-blind randomised controlled trial investigating the effects of dietary nitrate supplementation on acclimatisation to hypobaric hypoxia at high altitude in healthy human volunteers. The primary outcome measure was the change in oxygen efficiency during exercise at high altitude between participants allocated to receive nitrate supplementation and those receiving a placebo. A number of secondary measures were recorded, including exercise capacity, peripheral and microcirculatory blood flow and tissue oxygenation. Results from this study will further elucidate the role of NO in adaption to hypoxaemia and guide clinical trials in critically ill patients. Improved understanding of hypoxaemia in critical illness may provide new therapeutic avenues for interventions that will improve survival in critically ill patients.

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More information

Published date: 10 September 2013
Keywords: critical care, exercise, high altitude, hypoxaemia, hypoxia, microcirculation, nitric oxide
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 358867
URI: http://eprints.soton.ac.uk/id/eprint/358867
ISSN: 1551-7144
PURE UUID: 37cd26f7-24f2-4b94-8d7f-d548cd85d1d1
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 14 Oct 2013 14:27
Last modified: 18 Jul 2017 03:25

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Contributors

Author: Daniel S. Martin
Author: Edward T. Gilbert-Kawai
Author: Paula M. Meale
Author: Bernadette O. Fernandez
Author: Alexandra Cobb
Author: Maryam Khosravi
Author: Kay Mitchell
Author: Denny Z.H. Levett
Author: Michael G. Mythen
Author: Martin Feelisch ORCID iD

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