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The following is a critical appraisal of a journal article “Exercise Training in Mitochondrial Myopathy: A Randomised Controlled Trial” by Cejudo, Bautista et al. (2005). This appraisal has been written as an assignment for the unit Health, Disease and Exercise at the University of Canberra.

What is the background to this research?
Mitochondria are present in all human cells (except red blood cells), and convert the nutrients from food into energy for cellular functioning. This process relies on oxygen and is termed aerobic metabolism. Mitochondrial Myopathy (MM) is a genetic disease which affects the mitochondria of muscle cells. Patients with MM commonly report muscle fatigue, lethargy, pain, and exercise intolerance, as the ability of the mitochondria to produce energy in the muscles is affected. The degree that MM impacts function and quality of life is varied among patients. In severe cases, symptom onset can present in response to basic activities of daily living (ADLs), while other cases may tolerate more prolonged bouts of activity. Experience of symptom worsening as a result of exercise is a common barrier to regular physical activity participation. Exercise intolerance as a feature of MM is considered to be a combination of general deconditioning and a reduced oxidative capacity due to the genetically determined limitations of the energy-yielding mitochondria.

This research built upon established literature demonstrating the benefits of aerobic exercise in MM. This paper was the first to program upper body resistance, and lower body endurance exercises to determine the impact of combined aerobic exercise on exercise capacity, quality of life, and clinical symptom measures in patients with MM.

Where is this research from?
The study was carried out by researchers from Virgen del Rocío University Hospital and the Hospital 12 de Octubre in Spain. The study was published in September 2005 in Muscle & Nerve, a peer-reviewed medical journal dedicated to neuromuscular disorders and treatment options, but requires payment or subscription for access.

What kind of research was this?
This study was a randomised control trial (RCT), a research method which randomly distributes subjects into groups: the experimental training group(s) being researched, and the disease control group for comparison. RCTs are the most rigorous method to establish a cause-effect relationship between an intervention and the experiment outcome.

What did the research involve?
Twenty (10 male, 10 female) subjects were eligible for participation, meeting the inclusion criteria of mitochondrial myopathy diagnosis, exercise intolerance or active muscle pain, and a VO₂ max score less than 83% of age-predicted values. Subjects were divided into a training group or a control group.

All subjects undertook baseline exercise, quality of life, and clinical symptom assessments before and after completing a 12-week intervention. Exercise capacity was measured by the symptom-limited maximal cycle test, shuttle walking test, submaximal cycling endurance test, subjective end-test exertion and leg fatigue, and the peripheral muscle strength test. Quality of life was assessed with the Nottingham Health Profile (NHP) questionnaire. Clinical symptoms were captured with a symptoms questionnaire, and pulmonary function/ventilatory muscle strength testing.

Control Group:
 * Pre- and post-intervention testing

Training Group:
 * Pre- and post-intervention testing
 * Intervention: 60 minutes endurance exercise, 3 days a week for 12 weeks

Cycling was maintained at 70% baseline peak physical work rate for the 12-week duration. 1RM strength testing was conducted fortnightly, and with any change from the baseline score, weights were adjusted to maintain 50% of 1RM throughout the study. Upper body resistance exercises started at one set of 10-15 reps, and gradually progressed to 2-3 sets with increased capacity.

What were the basic results?
Exercise capacity measures:
 * 28.5% average increase in VO₂ max
 * Increase in 1RM ranging 32-62%
 * Average 62% time increase, and 68.9% distance increase in the endurance cycle test.
 * Average increase 95 metres in shuttle-walk test
 * All patients increased loads lifted, or repetitions performed in arm strength exercises
 * Decreased subjective end-test exertion

Quality of life measures:
 * Average increase of 21.47% in quality of life
 * Improved mobility and fatiguability

Clinical symptom measures:
 * Muscle pain, cramps and fatigue symptoms decreased in severity or disappeared
 * Increase in pulmonary function

Performing submaximal upper body strength and lower body endurance training in combination permitted an increase in aerobic endurance capacity, without aggravating MM symptoms. The reversal of deconditioning and an increase in oxidative capacity influenced self-report mobility and fatiguability, with the potential to further improve functionality, quality of life, and symptom decline

What conclusions can we take from this research?
Higher physical activity is associated with lower symptom severity in MM patients. Endurance exercise training promotes the formation of new muscular mitochondria and blood vessels, decreasing the burden on existing mitochondria, and increasing activity tolerance. The most rapid and dramatic mitochondrial changes in response to exercise will occur in deconditioned patients during the first 6 weeks of physical activity, but stopping exercise will result in a complete reversal of gains (detraining) in just 8 weeks. Beyond MM disease maintenance, regular endurance and resistance exercise fosters protection against the development of chronic disease including heart disease, hypertension, cancer, and type 2 diabetes.

Practical advice
Despite the benefits of controlled exercise in MM, the individual variations of symptom presentation and severity among patients warrants supervision surrounding novel physical activity participation. 48% of MM patients are overweight or obese and carry an increased chronic disease risk. Doctor clearance before commencing a new exercise regime is recommended, and working with an accredited exercise specialist can assist with appropriately tailored exercise programming and symptom monitoring.