Amyotrophic lateral sclerosis (ALS) is a disorder of motor neurons that usually leads to death over months to years. There is no cure. Ever since Lou Gehrig, a famous athlete, was diagnosed with the disease in the late 1930s, there has been interest in the relationship between physical activity and the development of ALS—with some studies suggesting a higher risk with increasing activity, presumably due to oxidative stress leading to neuronal loss. In a large, population-based, case-control study, Pupillo and colleagues (2014) aimed to explore this relationship more rigorously.
The authors conducted a study lasting >4 years that captured newly diagnosed ALS cases in a large European consortium. Eligible patients were older than 18 years and were diagnosed with possible, probable, or definitive ALS based on established criteria. For each case, general practitioners in the area recruited two controls matched for sex, age (within 2.5 years), and location. In addition to collection of baseline data, cases and controls underwent a structured interview including occupational history, sport and leisure activities, physical activity, and a history of trauma. Sport-related and physical activity–related exercise was converted to estimations of metabolic equivalents (METs) for each activity and multiplied by the number of years and hours per week spent on the activity to create a cumulative MET score for each subject.
A total of 652 patients with ALS and 1166 controls were included in the study, and risks were calculated using logistic regression. Median age was 66 among the cases and 67 among controls. Median body mass index (BMI) was 23.9 for cases and 25.7 among controls. Of the ALS patients, 301 were diagnosed with definite ALS, 276 with probable ALS, and 75 with possible ALS.
The authors found that overall physical activity was associated with a significantly reduced risk of developing ALS [adjusted odds ratio (OR), 0.65; 95% confidence interval (CI), 0.48–0.87], as were work-related physical activity (adjusted OR, 0.56; 95% CI, 0.36–0.87) and participation in organized sports (adjusted OR, 0.49; 95% CI, 0.32–0.75). Higher cumulative MET scores were inversely correlated with the risk of development of ALS.
When examining traumatic injuries, the authors found that only a history of more than one head trauma was associated with an increased risk of having ALS (OR, 2.82; 95% CI, 1.22–6.56). The overall incidence of traumatic injuries was not found to be significantly different between cases and controls. Mean age of ALS onset was 67.1 years in patients who were more physically inactive and 61.5 years in those with a history of work-related or sport-related physical activity (p<.0001), although this relationship was attenuated when the data were adjusted by birth cohort.
This important study demonstrates that physical activity is not a risk factor for the development of ALS and may actually be protective—in contrast to other previous studies as well as anecdotal evidence from a number of high-profile ALS cases in athletes. There certainly are limitations to the study, including possible recall bias and the lack of blinding among the interviewers. However, this work stands as perhaps the best evidence yet that addresses the relationship between physical activity and ALS. Patients newly diagnosed with the disease often ask clinicians whether a variety of exposures may have been the cause; this study eliminates physical activity from that possible list.
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