Rodriguez‐Miguelez and coworkers effectively contend that skeletal muscle oxidative capacity is altered in cystic fibrosis (CF) patients (Rodriguez‐Miguelez et al. 2017), based only on past results of in vitro studies in cultured cells and their own in vivo observations in skeletal muscle in CF patients (Erickson et al. 2015). In contrast to what Rodriguez‐Miguelez and coworkers claim in their case argument in this CrossTalk discussion (Rodriguez‐Miguelez et al. 2017), observations in the three cited ‘corroborating’ in vivo studies of oxidative metabolism in CF skeletal muscle (de Meer et al. 1995; Wells et al. 2011; Erickson et al. 2015) do not support their hypothesis.
First, it is important to accept that near infrared spectroscopy (NIRS) measurements of oxidative capacity in skeletal muscles cannot distinguish between a lower mitochondrial number and/or a decline in mitochondrial function (Erickson et al. 2015). Additionally, adipose tissue thickness (> 2 cm) will impede NIRS light penetration, which limits this method to non‐obese populations (Erickson et al. 2015).
Second, de Meer et al. only reported altered muscle energy balance during dynamic exercise in CF patients compared to healthy controls (de Meer et al. 1995). Post‐exercise phosphocreatine (PCr) recovery kinetics reporting independently on mitochondrial function (Meyer, 1988) were, however, not determined (de Meer et al. 1995). Therefore it was not established whether a reduction in oxidative capacity or contractile efficiency contributed to altered muscle energy balance during exercise.
Recently, we reported a similar observation of altered muscle energy balance during dynamic exercise in patients with a fatty acid oxidation disorder (Diekman et al. 2016). In that study, however, the underlying cause was not failing mitochondrial function; rather, it may be explained by a slow‐to‐fast shift in quadriceps fibre‐type composition. The measured rates of PCr and Pi recovery post‐exercise showed that the mitochondrial capacity for ATP synthesis in the quadriceps muscle was normal (Diekman et al. 2016).
With respect to the cited corroborating study by Wells and coworkers, the data show that post‐exercise in vivo phosphocreatine recovery kinetics in skeletal muscle of CF patients were, in fact, unchanged from healthy controls in two out of three exercise tests (Wells et al. 2011). Therefore, on the basis of the outcome of that study alone, the hypothesis that oxidative capacity of skeletal muscle in CF is altered has already been rejected (Popper, 1934), because a primary intrinsic defect should always be present, not just in 1 out of 3 tests. Furthermore, our recent report of a normal oxidative capacity of leg muscles in adolescents with CF (Werkman et al. 2016) was corroborated independently by the findings reported by Decorte and coworkers (Gruet et al. 2016; Decorte et al. 2017). They found similar in vivo metabolic skeletal muscle responses during exercise and recovery in adults with CF and healthy controls, and confirm the hypothesis that an altered oxidative capacity in patients with CF is untenable.
In conclusion, three in vivo studies verified a normal oxidative capacity of leg muscles in clinically stable (i.e. without any signs of systemic inflammation and/or chronic Pseudomonas aeruginosa colonization) patients with CF (Gruet et al. 2016; Werkman et al. 2016; Decorte et al. 2017). Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF. Further longitudinal studies could be performed aiming to describe the effects of chronic infection and inflammation on muscular function and training.
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Additional information
Competing interests
None declared.
Linked articles This article is part of a CrossTalk debate. Click the links to read the other articles in this debate: http://dx.doi.org/10.1113/JP272486, http://dx.doi.org/10.1113/JP272505 and http://dx.doi.org/10.1113/JP273739.
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