Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy

Miranda Nabben, Joep P.J. Schmitz, Jolita Ciapaite, Carlijn M.P. le Clercq, Natal A. van Riel, Harm R. Haak, Klaas Nicolay, Irenaeus F.M. de Coo, Hubert Smeets, Stephan F. Praet, Luc J. van Loon, Jeanine J. Prompers

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Muscle weakness and exercise intol erance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min-1·kg body wt-1, maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt-1·day-1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using31P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.

Original languageEnglish
Pages (from-to)R689-R701
Number of pages13
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume312
Issue number5
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

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Mitochondrial Myopathies
Nitrates
Exercise
Oxygen
Costs and Cost Analysis
Muscles
Dietary Supplements
Workload
Phosphocreatine
Muscle Weakness
Oxygen Consumption
Athletes
Skeletal Muscle
Magnetic Resonance Spectroscopy
Quality of Life

Cite this

Nabben, Miranda ; Schmitz, Joep P.J. ; Ciapaite, Jolita ; le Clercq, Carlijn M.P. ; van Riel, Natal A. ; Haak, Harm R. ; Nicolay, Klaas ; de Coo, Irenaeus F.M. ; Smeets, Hubert ; Praet, Stephan F. ; van Loon, Luc J. ; Prompers, Jeanine J. / Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2017 ; Vol. 312, No. 5. pp. R689-R701.
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abstract = "Muscle weakness and exercise intol erance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min-1·kg body wt-1, maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt-1·day-1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50{\%} of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using31P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.",
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author = "Miranda Nabben and Schmitz, {Joep P.J.} and Jolita Ciapaite and {le Clercq}, {Carlijn M.P.} and {van Riel}, {Natal A.} and Haak, {Harm R.} and Klaas Nicolay and {de Coo}, {Irenaeus F.M.} and Hubert Smeets and Praet, {Stephan F.} and {van Loon}, {Luc J.} and Prompers, {Jeanine J.}",
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Nabben, M, Schmitz, JPJ, Ciapaite, J, le Clercq, CMP, van Riel, NA, Haak, HR, Nicolay, K, de Coo, IFM, Smeets, H, Praet, SF, van Loon, LJ & Prompers, JJ 2017, 'Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 312, no. 5, pp. R689-R701. https://doi.org/10.1152/ajpregu.00264.2016

Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy. / Nabben, Miranda; Schmitz, Joep P.J.; Ciapaite, Jolita; le Clercq, Carlijn M.P.; van Riel, Natal A.; Haak, Harm R.; Nicolay, Klaas; de Coo, Irenaeus F.M.; Smeets, Hubert; Praet, Stephan F.; van Loon, Luc J.; Prompers, Jeanine J.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 312, No. 5, 01.05.2017, p. R689-R701.

Research output: Contribution to journalArticle

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AU - Schmitz, Joep P.J.

AU - Ciapaite, Jolita

AU - le Clercq, Carlijn M.P.

AU - van Riel, Natal A.

AU - Haak, Harm R.

AU - Nicolay, Klaas

AU - de Coo, Irenaeus F.M.

AU - Smeets, Hubert

AU - Praet, Stephan F.

AU - van Loon, Luc J.

AU - Prompers, Jeanine J.

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