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Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - a randomised controlled trial (Xtreme Alps)

Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - a randomised controlled trial (Xtreme Alps)
Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - a randomised controlled trial (Xtreme Alps)

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 μM) and at day 5 (D5) of high altitude (22.9 vs 84.3 μM, p < 0.001). Dietary nitrate supplementation also significantly increased both plasma nitrite (0.78 vs. 0.86 μM SL, 0.31 vs. 0.41 μM D5, p = 0.03) and total nitroso product (11.3 vs. 19.7 nM SL, 9.7 vs. 12.3 nM D5, p < 0.001) levels both at sea level and at 4559 m. However, plasma nitrite concentrations were more than 50% lower at 4559 m compared to sea level in both treatment groups. Despite these significant changes, dietary nitrate supplementation had no effect on any measured read-outs of sublingual or forearm blood flow, even when environmental hypoxia was experimentally reversed using supplemental oxygen. In conclusion, dietary nitrate supplementation does not improve microcirculatory function at 4559 m.

1089-8603
27-35
Cumpstey, Andrew F
cd040417-5e62-41d2-8640-1ec8905858a7
Hennis, Philip J
b3563308-2f8e-49fb-a73f-c5afcc177ffe
Gilbert-Kawai, Edward T
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Fernandez, Bernadette O
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Grant, Daniel
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Jenner, William
87440735-1775-4334-84cf-e7426a6a7fed
Poudevigne, Matthieu
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Moyses, Helen
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Levett, Denny Zh
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Cobb, Alexandra
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Meale, Paula
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Mitchell, Kay
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Pöhnl, Helmut
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Mythen, Monty G
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Grocott, Michael Pw
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Martin, Daniel S
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Feelisch, Martin
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Cumpstey, Andrew F
cd040417-5e62-41d2-8640-1ec8905858a7
Hennis, Philip J
b3563308-2f8e-49fb-a73f-c5afcc177ffe
Gilbert-Kawai, Edward T
2d1f0dd7-023f-4313-b513-0a1705daa71a
Fernandez, Bernadette O
9890aabc-1fe6-4530-a51e-31182e537131
Grant, Daniel
f69ed25c-dde1-4814-9ed1-e0999b92538a
Jenner, William
87440735-1775-4334-84cf-e7426a6a7fed
Poudevigne, Matthieu
7522102d-91ef-4c8b-b2a1-4e92a7a818e6
Moyses, Helen
56434d9c-870f-4539-a66a-c791add44f67
Levett, Denny Zh
1743763a-2853-4baf-affe-6152fde8d05f
Cobb, Alexandra
7e071e58-7ce9-46e9-b8b8-d201f71a9a02
Meale, Paula
92c84a2a-1392-4f4b-bbbd-8cb8009b553f
Mitchell, Kay
95e389c6-29e2-46d4-b869-eb7f9ff2b49d
Pöhnl, Helmut
c8eac2c4-c1fd-42e2-be10-4278862baefb
Mythen, Monty G
266ffcca-f8dd-49b4-abe4-0ffb035e2b35
Grocott, Michael Pw
1e87b741-513e-4a22-be13-0f7bb344e8c2
Martin, Daniel S
3e441b48-9221-4308-8ae6-49cbde20753f
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd

Cumpstey, Andrew F, Hennis, Philip J, Gilbert-Kawai, Edward T, Fernandez, Bernadette O, Grant, Daniel, Jenner, William, Poudevigne, Matthieu, Moyses, Helen, Levett, Denny Zh, Cobb, Alexandra, Meale, Paula, Mitchell, Kay, Pöhnl, Helmut, Mythen, Monty G, Grocott, Michael Pw, Martin, Daniel S and Feelisch, Martin (2019) Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - a randomised controlled trial (Xtreme Alps). Nitric Oxide, 94, 27-35. (doi:10.1016/j.niox.2019.10.004).

Record type: Article

Abstract

Native highlanders (e.g. Sherpa) demonstrate remarkable hypoxic tolerance, possibly secondary to higher levels of circulating nitric oxide (NO) and increased microcirculatory blood flow. As part of the Xtreme Alps study (a randomised placebo-controlled trial of dietary nitrate supplementation under field conditions of hypobaric hypoxia), we investigated whether dietary supplementation with nitrate could improve NO availability and microvascular blood flow in lowlanders. Plasma measurements of nitrate, nitrite and nitroso species were performed together with measurements of sublingual (sidestream dark-field camera) and forearm blood flow (venous occlusion plethysmography) in 28 healthy adult volunteers resident at 4559 m for 1 week; half receiving a beetroot-based high-nitrate supplement and half receiving an identically-tasting low nitrate 'placebo'. Dietary supplementation increased plasma nitrate concentrations 4-fold compared to the placebo group, both at sea level (SL; 19.2 vs 76.9 μM) and at day 5 (D5) of high altitude (22.9 vs 84.3 μM, p < 0.001). Dietary nitrate supplementation also significantly increased both plasma nitrite (0.78 vs. 0.86 μM SL, 0.31 vs. 0.41 μM D5, p = 0.03) and total nitroso product (11.3 vs. 19.7 nM SL, 9.7 vs. 12.3 nM D5, p < 0.001) levels both at sea level and at 4559 m. However, plasma nitrite concentrations were more than 50% lower at 4559 m compared to sea level in both treatment groups. Despite these significant changes, dietary nitrate supplementation had no effect on any measured read-outs of sublingual or forearm blood flow, even when environmental hypoxia was experimentally reversed using supplemental oxygen. In conclusion, dietary nitrate supplementation does not improve microcirculatory function at 4559 m.

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Accepted/In Press date: 7 October 2019
e-pub ahead of print date: 8 October 2019

Identifiers

Local EPrints ID: 435562
URI: http://eprints.soton.ac.uk/id/eprint/435562
ISSN: 1089-8603
PURE UUID: 0508af69-484c-48f4-81b5-5301f5cb2f1b
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 Pw 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: 11 Nov 2019 17:30
Last modified: 19 Apr 2024 17:36

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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: Daniel Grant
Author: William Jenner
Author: Matthieu Poudevigne
Author: Helen Moyses
Author: Denny Zh Levett
Author: Alexandra Cobb
Author: Paula Meale
Author: Kay Mitchell ORCID iD
Author: Helmut Pöhnl
Author: Monty G Mythen
Author: Daniel S Martin
Author: Martin Feelisch ORCID iD

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