A new study shows that patients with amyotrophic lateral sclerosis (ALS) experience decreased oxidative metabolism during exercise, and that differences among individuals in exercise capacity matches ALS clinical heterogeneity.
The study, titled, “Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise,” was published in the journal Nature.
The study is new because it is the first to explore the journey of oxygen from the lung to metabolic use in skeletal muscles during exercise in patients in ALS.
From the earliest phase of the disease, ALS patients experience decreased exercise tolerance, and it progresses to a point of complete limitation of activities of daily living.
Researchers at the University of Milano-Bicocca set out to investigate for the first time the efficiency of oxygen transport, which involves the passage of oxygen from the lung to the arteries to organ delivery, and then oxygen use in skeletal muscles, during exercise in patients with ALS (NCT02548663).
Oxidative metabolism refers to the use of oxygen by mitochondria, which provides people with energy to conduct activities. Skeletal muscles are the main muscles that are used to conduct exercise, and oxidative metabolism is necessary by these muscles for the continuation of activity.
Exercise increases the metabolic demand of skeletal muscles in patients with ALS, and therefore this study will help scientists understand if there is an impairment in oxidative metabolism in ALS.
Seventeen patients diagnosed with ALS were recruited for this study. An exercise tolerance test was performed at baseline (at recruitment) and four months later. The results were compared to 13 healthy age- and sex-matched controls.
Exercise tolerance was assessed by measuring peak oxygen uptake using a cardiopulmonary exercise test (CPET) on a cycle ergometer, a method called near infrared spectroscopy (NIRS), and through breathing pattern. NIRS is a non-invasive method that gives an estimation of oxygen extraction by skeletal muscles in both healthy people and patients and has been used to determine impairment of oxygen metabolism in ALS patients.
Results showed that patients with ALS had a 44% lower peak oxygen uptake than control patients. In addition, ALS patients had a 43% decreased oxidative metabolism function in skeletal muscles. There was correlation between these two variables.
Additionally, patients with ALS had 46% lower pulmonary ventilation, the result of an inefficient breathing pattern due to an increase in respiratory frequency from the beginning to the end of the exercise period.
Researchers also discovered that there was a slight positive correlation between peak oxygen uptake and ALS clinical scores, particularly in ALS patients with a bulbar onset. Therefore, the higher the peak oxygen uptake in patients, the higher the ALS function rating score. Higher ALSFRS-R scores denote that more functioning is retained.
They also showed that the higher the peak oxygen uptake, the lower the disease progression index in patients with a disease progression index of 0.65 or above. Lastly, researchers found that the higher the MNA score, which measures nutritional status, the higher the ALSFRS-R score.
This current data revealed that there is an impairment of skeletal muscle oxidative metabolism function, which may be explained by an incomplete activation of muscles due to progressive impairment of motor neurons in ALS. This inefficiency in metabolism is related to the individual exercise capacity and functioning of ALS patients.
The measurement of peak oxygen uptake and muscle oxygen extraction using the NIRS method might represent a valuable tool in determining the variable clinical expression of ALS, and these factors could be used in the future to determine prognosis of patients, researchers concluded.
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