Is Exercise a Risk Factor for A.L.S?

Check out this answer from Consensus:

The relationship between physical activity and ALS is complex and appears to be influenced by genetic predisposition and other confounding factors. While some studies suggest that strenuous physical activity may increase the risk of ALS, particularly in individuals with specific genetic profiles, other high-quality epidemiological studies do not support this association. Further research focusing on at-risk genotypes and large-scale studies are needed to confirm these findings and provide more definitive answers.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The etiology of ALS is multifactorial, involving both genetic and environmental factors. One environmental factor that has garnered significant attention is physical activity. This article aims to explore whether exercise is a risk factor for ALS by reviewing the current literature on the subject.

Evidence Supporting Exercise as a Risk Factor

Systematic Reviews and Meta-Analyses

Several systematic reviews have investigated the relationship between physical activity and ALS. One comprehensive review found that while cumulative measures of physical activity as a risk factor for ALS remain inconclusive, there is a significantly higher number of ALS cases among professional soccer and American football players, as well as a slightly increased risk in varsity athletes1. Another systematic review focused on contact sports and found that professional sports involving repetitive concussive head and cervical spinal trauma are associated with a substantially greater risk of ALS4.

Genetic and Molecular Studies

Recent studies using Mendelian randomization and transcriptomic analyses have provided more direct evidence supporting a causal relationship between strenuous leisure-time exercise and ALS. These studies found that genes with altered expression in response to acute exercise are enriched with known ALS risk genes, including C9ORF72. This suggests that exercise may cause motor neuron injury in individuals with a genetic predisposition to ALS2 5.

Animal Models

Research using transgenic mouse models of ALS has shown that the effect of exercise on disease onset and progression can vary by sex. In one study, exercise delayed the onset of disease in female mice but not in male mice, suggesting a possible neuroprotective effect of female sex hormones3.

Evidence Against Exercise as a Risk Factor

Epidemiological Studies

Contrary to the findings mentioned above, some epidemiological studies have concluded that physical activity is not a risk factor for ALS. A literature review of epidemiological studies found that the majority of high-quality studies did not support an association between physical activity and ALS risk7. Another study found no significant difference in the level of vigorous physical activities, including marathons and triathlons, between ALS patients and controls9.

Confounding Factors

Several studies have highlighted the role of confounding factors such as smoking, alcohol use, and body mass index in the relationship between physical activity and ALS. For instance, one study found that smoking increased the risk of ALS, while alcohol use decreased it, but no significant association was found with physical activity10.

Is exercise a risk factor for A.L.S?

Antonio Musaro has answered Unlikely

An expert from Sapienza University of Rome in Neuroscience

To date a causal link between exercise and ALS remain inconclusive. However, it has been reported, in cohort studies, a significantly higher number of cases of ALS in professional soccer and football players. Nevertheless, further research is necessary to also define the numerous confounding factors that may arise in this field. ALS is indeed a multi-factorial and multi-systemic disease.

Is exercise a risk factor for A.L.S?

Luc Dupuis has answered Likely

An expert from Inserm in Neurology

Epidemiological evidence suggest an association between fitness, leanness and ALS. People with history of physical activity and/or better fitness than the general population are more at risk for developing later ALS. Indeed, there are several studies pointing to increased risk in former athletes. Exercise might thus be a risk factor for ALS. However, this remains a correlation, which does not mean that exercise favors the development of ALS. It could also be that people with a specific cardiovascular/fitness profile are both at risk of developing ALS and of becoming athletes, both being independent. Experimental research in models is less clear for a direct relationship between exercise and ALS progression. More research is needed to ascertain cause to effect relationships.

Is exercise a risk factor for A.L.S?

Francesca Lanfranconi has answered Unlikely

An expert from University of Milano Bicocca in Physiology, Sports Science, Medicine

A large investigation based on 652 patients with ALS (European population-based registries), showed that physical activity is not a risk factor for ALS and may eventually be protective against the disease (Pupillo et al, 2014). Thus, we do not have evidence that exercise, strenuous or not, can increase the risk of having ALS.

Another hot field of research, is if tailored exercise programs can be used to counteract the progressive disuse of muscle affected by motor neuron disease. In the next 2 years we will have the results emerging from studies where this hypothesis has been tested.

Is exercise a risk factor for A.L.S?

Pavle Andjus has answered Extremely Unlikely

An expert from University of Belgrade in Neurobiology

Pupillo E, Messina P, Giussani G, Logroscino G, Zoccolella S, Chiò A, Calvo A,

Corbo M, Lunetta C, Marin B, Mitchell D, Hardiman O, Rooney J, Stevic Z,

Bandettini di Poggio M, Filosto M, Cotelli MS, Perini M, Riva N, Tremolizzo L,

Vitelli E, Damiani D, Beghi E; EURALS Consortium. Physical activity and

amyotrophic lateral sclerosis: a European population-based case-control study.

Ann Neurol. 2014 May;75(5):708-16.

RESULTS:

Overall physical activity was associated with reduced odds of having ALS (Adj OR=0.65, 95% CI=0.48-0.89) as were work-related physical activity (Adj OR=0.56, 95% CI=0.36-0.87) and organized sports (Adj OR=0.49, 95% CI=0.32-0.75). An inverse correlation was observed between ALS, the duration of physical activity (p=0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR=0.34, 95% CI=0.21-0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events.

INTERPRETATION:

Physical activity is not a risk factor for ALS and may eventually be protective against the disease.

Is exercise a risk factor for A.L.S?

Pablo Izquierdo has answered

An expert from University College London in Neuroscience, Physiology, and Pharmacology

Exercise may help prevent ALS but certain sports may carry greater risk