Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy

Abstract

Exercise intolerance is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still unsettled whether exercise training is safe and beneficial for patients with MM. To address this, we studied the effect of 12 weeks cycle training on exercise capacity, quality of life and underlying molecular and cellular events in five patients with single large-scale deletions, one with a microdeletion and 14 with point mutations of mitochondrial DNA (mtDNA), and 13 healthy subjects. Each training session lasted 30 min, and was performed at an intensity of 70% of VO2max (maximal oxygen uptake). Each subject performed 50 training sessions in 12 weeks. All subjects were evaluated before and after training, and 13 MM patients were studied after 8 weeks of deconditioning. Evaluation included VO2max and mutation load and mtDNA quantity, mitochondrial enzymatic activity, and number of centrally nucleated, apoptotic, ragged red and cytochrome oxidase (COX)-negative fibres in muscle biopsies from the quadriceps muscle. After 12 weeks of training, VO2max and muscle citrate synthase increased in MM (26 and 67%) and healthy (17 and 65%) subjects, while mtDNA quantity in muscle only increased in the MM patients (81%). In the MM patients, training did not change mtDNA mutation load in muscle, mitochondrial enzyme complex activities, muscle morphology and plasma creatine kinase. After deconditioning, VO2max and citrate synthase activity returned to values before training, while muscle mtDNA mutation load decreased. These findings show that aerobic training efficiently improves oxidative capacity in MM patients. Based on unchanged levels of mutant load in muscle, morphological findings on muscle biopsy and plasma creatine kinase levels during training, the treatment appears to be safe. Regular, supervised aerobic exercise is therefore recommended in MM patients with the studied mutations.

Endurance Exercise Training in Young Adults with Barth Syndrome: A Pilot Study

“…Endurance exercise training has also been found to be safe and improve peak exercise tolerance and cardiac and skeletal muscle function in conditions that share similar characteristics as BTHS: mitochondrial myopathies (Cejudo et al 2005;Jeppesen et al 2006Jeppesen et al , 2009 and congestive heart failure (Coats et al 1992;Delagardelle et al 2002;Giannuzzi et al 2003;Bartlo 2007). In patients with other mitochondrial myopathies, an endurance exercise program (3-5Â/week, 12 weeks, 70% VO 2peak ) increased peak oxygen consumption 23-29% and peak work rate 16-100% (Cejudo et al 2005;Jeppesen et al 2006Jeppesen et al , 2009. Also, 14 weeks of endurance exercise training increased peak oxygen consumption (~25%), peak skeletal muscle oxygen extraction (20%), and mitochondrial function, enzyme activity and volume (~50%) without an improvement in cardiac function in individuals with mitochondrial myopathies.…”

“…Most importantly, endurance exercise training in patients with non-BTHS heart failure was safe, improved survival (Belardinelli et al 1999), decreased hospitalization (Belardinelli et al 1999), and increased quality of life (Coats et al 1992;Tyni-Lenne et al 1996;Belardinelli et al 1999). Similarly, endurance exercise training has been found to be safe, improve exercise capacity, increase skeletal muscle oxygen extraction, and improve quality of life in individuals with other non-BTHS mitochondrial myopathies (Taivassalo et al 2001;Cejudo et al 2005;Jeppesen et al 2006Jeppesen et al , 2009. However, the effect of endurance exercise training on these measures in BTHS is unknown.…”

Endurance exercise ameliorates low birthweight developed catch-up growth related metabolic dysfunctions in a mouse model

“…thies [12]. As skeletal muscle is the major targets of regular endurance exercise, some investigations indicated that mitochondria may be the key of long-term exercises ameliorate diseases [13].…”

The Elusive Magic Pill: Finding Effective Therapies for Mitochondrial Disorders

“…Exercise promises to be an effective therapeutic intervention in patients with both primary and secondary mitochondrial disease. Although future clinical trials need to be performed, clinicians should be prescribing a supervised exercise program to patients affected by mitochondrial disease, as it has been found to be safe and effective as a therapy [33,34].…”