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The cause of amyotrophic lateral sclerosis (ALS) remains elusive, although several studies have strived to elucidate possible factors related to this devastating disease. Recently, cigarette smoking has been claimed to be a risk factor for ALS,1 but the biological basis of its action is still uncertain. Some studies have been devoted to the assessment of physical activity and physical prowess, driven by the common observation that many ALS patients, in particular younger patients, had been athletes or physically very active. A recent revision of literature on physical activity in ALS concluded that evidence from epidemiological research remains conflicting and inconclusive.2 However, this conclusion has been based on the paucity of methodologically sound papers on this topic. Mattson et al3 present a well-designed epidemiological study on a large cohort of over 680 000 Swedish male subjects born between 1951 and 1965 assessing the risk of developing ALS in relation to physical fitness, evaluated at the time of the military service conscription examination. They found that the risk of developing ALS was related to a higher weight-adjusted physical fitness during young adult life, while physical fitness per se, muscle strength, resting heart rate and other measures were not risk factors. Interestingly, while the height of cases and controls was similar, patients' weight was lower than that in controls. This observation is in keeping with the results of a case–control study showing that ALS patients reported they had always been slim or varsity athletes more likely than controls.4 Unfortunately, Mattson et al3 did not specifically investigate the participation to sport competitions.
This study offers a new perspective to look at the relationship between physical activity and ALS. As the authors suggest, a common body phenotype could underlie both fitness and ALS, characterised by relatively more type 1 muscle fibres (slow-twitch fibres), typical of endurance athletes. We found similar results in Italian professional soccer players, where the higher risk for ALS was found among midfielders, a role characterised by both a higher maximal oxygen uptake relative to body mass (a marker of aerobic power) and a higher proportion of lean body mass.5
Accordingly, ALS will not be related to sport participation or more strenuous physical activity but it will be related to a higher body fitness, which, in turn, predisposes to practice physical activity and sport. It is now generally accepted that weight-adjusted physical fitness, as well as physical fitness in general, is partially related to genetic components. Genome-wide association screening studies are currently ongoing on both sporadic ALS and physical fitness.
A comparative analysis of the findings of these studies could hopefully reveal single genes or genetic pathways shared by ALS and physical fitness and therefore shed new light on the mystery of ALS pathogenesis.