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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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(-1) inorganic nitrate (similar to 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 using P-31-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
Issue number5
Publication statusPublished - 1 May 2017


  • mitochondrial myopathy
  • nitrate
  • P-31-magnetic resonance spectroscopy
  • (V) over dot(O2peak)
  • permeabilized muscle fibers
  • O-2 COST


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