Efficiency of energy transfer during exercise: what are the limiting factors?

Steady-state exercise at high intensity evokes specific oxygen demands. The expected increase in oxygen uptake () is supplemented by a slow component (), indicative of work inefficiency within locomotor muscles (e.g. quadriceps femoris). The underlying mechanisms contributing to work inefficiency remain speculative. It has been postulated that work inefficiency may result from contractile (via an increased rate of ATP consumption per unit of power output; P/W) and/or mitochondrial (via a reduction in the ratio of ATP resynthesis per oxygen converted to water; P/O) source. ³¹Phosphorus-magnetic resonance spectroscopy (³¹P-MRS) is a more recent technique that enables the quantification of metabolites (including adenosine triphosphate, ATP; inorganic phosphate, P_i; phosphocreatine, PCr; and pH) and can provide insight into the energy status in skeletal muscle.

The simultaneous measurement of whole-body (via pulmonary gas exchange) and skeletal muscle ATP turnover (via ³¹P-MRS) during moderate and heavy bilateral knee-extension exercise recently enabled Cannon et al. (2014) to explore this physiological dilemma. They examined thirteen healthy male participants and one female participant whom they identified as being either recreationally active or an amateur competitive athlete. Pulmonary gas exchange measures provided evidence of work inefficiency (via the ) in heavy, but not moderate-intensity exercise. ³¹P-MRS measures further demonstrated changes in the concentration of PCr and total ATP turnover rate (ATP_tot) during the heavy exercise only. A strong relationship was also observed between [PCr] and oxygen uptake during heavy exercise. On average, change in ATP_tot during high-intensity exercise was not significantly different to slow component [PCr] ([PCr]_sc) and ; however, when looking at individual values, there were no significant correlations between change in ATP_tot and . Taken together, authors reported that work inefficiency during heavy exercise probably arises from both contractile and mitochondrial sources.

Cannon et al. (2014) used novel magnetic resonance spectroscopy techniques to examine the mechanism underlying contractile work inefficiency during high-intensity exercise. Specifically, the authors measured ATP_tot in all three bioenergetic pathways by quantifying the PCr recovery mechanics while measuring breath-by-breath . Contrary to previous estimations, the authors did not assume a linear relationship between and [PCr], yielding a more robust estimation of total ATP_tot. Indeed, the absence of this linear relationship during high-intensity exercise led the authors to conclude that is not solely attributed to contractile work inefficiency. Authors also implemented extensive familiarization and repeated test protocols in order to obtain reproducible physiological measurements and performances and eliminate any possible learning effects. The study design was further enhanced as the cadence of the knee extension was controlled to 90 min⁻¹ by the use of a metronome. As the MR-compatible ergometer was a flywheel, this minimized any discrepancies in resistance due to individuals’ kicking speed preferences.

The authors’ primary aim was to determine the source of inefficiency in the working muscle. However, they compared ATP_tot at the level of the muscle to measured from pulmonary gas exchange. While whole-body is a good indicator of muscle during submaximal intensities, pulmonary is not reflective of at the level of the working muscle during supramaximal intensities (Poole & Richardson, 1997). Moreover, Mortensen et al. (2008) propose that pulmonary is an inaccurate measure of muscle even during high-intensity submaximal exercise. These researchers measured whole-body and leg haemodynamics during cycling and knee-extension exercise. Their results suggest that while whole-body increases linearly until exhaustion, leg is attenuated as early as 50% of maximal aerobic capacity due to a plateau in leg blood flow (Mortensen et al. 2008). As Cannon et al. (2014) were measuring substrate utilization and dynamics at intensities corresponding to 80% of their maximal aerobic capacity, their conclusions on the mechanisms contributing to a remain speculative. The current study used bilateral knee-extension exercise that elicits a greater rate of blood flow to muscle mass than whole-body exercise, as measured by Mortensen and colleagues (2008), thereby preventing a direct comparison between these studies. Future research could use blood oxygen level-dependent functional magnetic resonance spectroscopy (BOLD fMRI) to measure tissue perfusion in the leg. However, as blood flow is suggested to be a limiting factor in muscle , conclusions regarding the source of locomotor inefficiency cannot be made without doing a direct measurement of in the working muscle.

The use of MRI to assess muscle energetics provides a considerably greater insight into our understanding of skeletal muscle metabolism. Notably, coil placement has a considerable effect on measured outcomes. To eliminate the variation caused by muscle recruitment and the use of different motor units, the quadriceps muscle should be investigated using electromyography (EMG) to determine the region with the highest activation during familiarization trials or testing. This would allow the coil to be focused on the most metabolically active region, thereby eliminating a potential source of variation.

The role of neuromuscular function and muscle recruitment was described as a potential source of heterogeneity in the current study. The present study examined differences between low (∼45–55% ) and moderate–high (∼halfway between lactate threshold and ) exercise intensity. It is unclear why the authors did not add a third maximal intensity group at ∼100–120% of power. This would have provided a more comprehensive view of energy production using aerobic, anaerobic and ATP/phosphocreatine energy systems. Moreover, including a supramaximal exercise intensity would help to better understand , especially because of the high phosphate cost of such high-intensity exercise_. An additional consideration for including a higher intensity exercise condition would enable the contributing effects of neuromuscular function to be better accounted for. Employing a design with three intensities would potentially allow for the examination of ATP turnover and kinetics based on level of muscle activation or fibre type (Rossiter et al. 2002).

The present study findings contribute to the growing number of skeletal muscle metabolism studies that have been conducted primarily in male partici-pants. The inclusion of one female participant is questionable and precludes the determination of possible sex differences in fat oxidation, muscle oxidative capacity and work efficiency. Willcocks et al. (2010) have documented that the [PCr] cost per watt was higher in females than males in the quadriceps muscle. This may suggest either decreased oxidative capacity or impaired exercise efficiency among females. Sex differences in fatigue during heavy exercise in adults have been associated with differences in the leg vasodilatory response, muscle fibre-type composition, and muscle activation patterns. Willcocks et al. (2010) also observed that the matching of oxygen delivery to oxygen demand was superior in males relative to females during quadriceps exercise. Exercise efficiency in females compared with males requires further investigation.

Both recreationally active and amateur competitive athletes were included in the current study. A detailed description of current physical activity and sport participation was not provided and probably increased heterogeneity in their study findings. Cannon et al. (2014) acknowledged a potential dissociation between [PCr]_sc and in endurance-trained athletes and differences in motor unit recruitment with varying fitness levels. It is unclear whether varying fitness levels had a significant influence on study findings; however, future work should better characterize physical activity (including activity mode, intensity, duration and frequency) and consider the influence of physical activity and competitive sport participation on work inefficiency.

In summary, Cannon et al. (2014) have used novel methods to reveal that work inefficiency during heavy exercise arises from both contractile and mitochondrial sources. The inclusion of additional methods (BOLD fMRI and EMG) as well as a third exercise condition (supramaximal exercise) may help to overcome current study limitations and expand our knowledge in this field of research. The study findings are very interesting and should be substantiated in larger cohorts, including females and individuals with varying fitness levels.

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Competing interests

None declared.