UK Biobank studies link physical activity to lower ALS risk

Study findings on physical activity and hazard ratios

The analysis of UK Biobank data included 384,836 participants with a median age of 57.0 years and a median follow-up period of 14.0 years. During this time, researchers recorded 541 incident diagnoses of ALS.

Self-reported physical activity also showed a lower risk, with a hazard ratio of 0.77 for high versus low activity levels.

Data revealed a non-linear relationship where risk was lowest at mid-range activity levels.

Genetic factors and ALS risk associations

Researchers examined how genetic markers interact with physical activity levels in the study cohort.

Among 535 C9ORF72 expansion carriers, there were 56 ALS events. The association between physical activity and ALS risk in these carriers was directionally consistent but not statistically significant.

EWAS study identifies 45 modifiable risk factors

Researchers in China published a study in Brain and Behavior titled "Identifying Modifiable Factors and Their Joint Effect on Amyotrophic Lateral Sclerosis: A Prospective Cohort Study in the UK Biobank". This research utilized an exposome-wide association study approach to analyze data from 326,050 participants in the UK Biobank aged 40 to 69.

The participants enrolled in the study between 2006 and 2010, and by the end of the follow-up period in October 2025, 744 individuals had developed ALS.

The study examined 184 factors across seven different areas, identifying 45 that were significantly associated with the risk of ALS. After applying a stricter statistical test, 12 of these factors remained significant.

Conversely, lower education levels, unemployment, and increased time spent watching television—which researchers interpreted as an indicator of physical inactivity—were associated with a higher risk.

Theoretical potential for ALS case prevention

Statistical modeling estimated a population attributable fraction of 25.9% in a conservative scenario where unfavorable factors were shifted to intermediate levels.

In a theoretical ideal scenario where all analyzed factors shifted to favorable levels, the model estimated that 87.4% of ALS cases could be avoided. Lifestyle factors accounted for 41.3% of that potential reduction in cases.

Researcher conclusions on modifiable risk factors

Despite these limitations, the researchers stated, "ALS may have greater preventive potential than we previously thought".

They concluded, "Interventions targeting modifiable risk factors, particularly those related to lifestyle and socioeconomic status, may help reduce the incidence of ALS".

General context of physical activity and health

This includes voluntary exercise and incidental activity like walking, cleaning, working, and active transport.

Increased activity improves physical, mental, cognitive, and cardiovascular health, whereas a lack of activity is linked to negative health outcomes. Activity also acts as a key regulator for controlling body weight and increasing energy expenditure. Differences in individual physical activity levels have a substantial genetic basis.

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