Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy.
Muscle weakness and exercise intolerance 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-1inorganic 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.
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.|Department of Genetics and Cell Biology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands.
Miranda
0000-0002-5691-1634
M
Nabben
Computational Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Joep P J
JPJ
Schmitz
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Jolita
J
Ciapaite
Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Carlijn M P
CMP
le Clercq
Computational Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Natal A
NA
van Riel
Department of Internal Medicine, Máxima Medical Center, Eindhoven, The Netherlands.|Department of Internal Medicine, CAPHRI School for Public Health and Primary Care, Ageing and Long-Term Care, Maastricht University Medical Center, Maastricht, The Netherlands.
Harm R
HR
Haak
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Klaas
K
Nicolay
Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Irenaeus F M
IFM
de Coo
Department of Genetics and Cell Biology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands.
Hubert
H
Smeets
Department of Rehabilitation Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; and.
Stephan F
SF
Praet
Department of Human Biology and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Luc J
LJ
van Loon
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; j.j.prompers@tue.nl.
Jeanine J
JJ
Prompers
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015444:Exercise; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000188:drug therapy* / Q000503:physiopathology*; D053580:Muscle Strength / Q000187:drug effects; D009566:Nitrates / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
D009566:Nitrates
31P-magnetic resonance spectroscopy; V̇o2peak; mitochondrial myopathy; nitrate; permeabilized muscle fibers