Moderate exercise in midlife is associated with a reduced risk for amyotrophic lateral sclerosis (ALS) later in life, but this benefit appears to be limited to men, findings from a large prospective study showed.
Men who reported moderate levels of physical activity had a 29% lower risk for ALS, whereas those with high levels of physical activity had a 41% lower risk for the disease.
The findings were published online on June 26 in Neurology.
Conflicting Findings
Several famous athletes have died of ALS, including the baseball player Lou Gehrig (for whom the disease is named), football players Dwight Clark, Steve Gleason, and Kevin Turner, and the boxer Ezzard Charles. This has led some scientists to speculate that intense physical activity may play a role in the development of the disease.
Anders M. Vaage, MD, noted there have been conflicting findings in previous studies on the topic, with results showing both increased and reduced ALS risks with increasing levels of physical activity.
In one study, researchers followed more than 212,000 Swedish cross-country skiers and more than 500,000 Swedish individuals in the general population for 20 years and found that strenuous cross-country skiing was associated with a higher risk for ALS but only among the best skiers; recreational skiers appeared to have a reduced risk.
"Our study does not necessarily contradict previous studies with findings of an increased ALS risk with extreme or intense levels of physical activity in athletes, as this study reflects more moderate levels of physical activity and fitness in the total population," said Vaage.
To further explore the association, the researchers followed 373,700 individuals who participated in a cardiovascular health survey for an average of 27 years. When the survey began, most participants were 40-42 years old.
Participants were followed until the date of ALS diagnosis, ALS death, death from other causes, emigration, or the end of study in August 2021.
Participants answered questions about physical activity levels, smoking status, and other issues relating to cardiovascular health, and participants' resting heart rate was measured and divided into quartiles of 31.65 beats per minute (BPM), 66-74 BPM, 75-81 BPM, or 82-100 BPM.
Participants self-reported their physical activity over the past year, classifying it into one of four categories: Sedentary, at least 4 hours per week of walking or cycling, at least 4 hours per week of recreational sports or heavy gardening, or regular participation in intense training or sports competitions several times per week.
Only a few participants reported the highest level of physical activity, so researchers combined the third and fourth categories into a single high-activity group.
Of the total study cohort, 504 participants developed ALS. Of those who developed the disease, 59% were men.
Researchers found that of the 41,898 male participants with the highest level of physical activity, 63 developed ALS. In comparison, of the 76,769 male participants who reported an intermediate level of physical activity, 131 developed ALS. Among the 29,468 male participants who reported the lowest level of physical activity, 68 developed ALS.
No Link in Women?
After adjusting for smoking, body mass index, and other risk factors, investigators found that men with moderate physical activity levels had a 29% lower risk for ALS compared with those with low physical activity levels, whereas those with the highest activity levels had a 41% lower risk.
In addition, men in the lowest of the four categories of resting heart rate had a 32% reduced risk for ALS compared with men with a higher resting heart rate.
Investigators are unclear why there was a lack of association between physical activity and resting heart rate and ALS risk in women.
"There are known sex differences in ALS, which includes a sex ratio with male preponderance, and there are also sex differences in response to physical exercise. Perhaps underlying mechanisms herein can explain the difference observed between males and females in the study," Vaage said. He noted that future research should explore this difference.
Study limitations included the absence of data on physical trauma and head trauma, which have been linked with increased ALS risk. In addition, there were no data on genotype.
In an accompanying editorial, Pamela Shaw, MD, and Johnathan Cooper-Knock, BMBCh, PhD, of the University of Sheffield, Sheffield, England, described the research as a "valuable contribution to the field and potentially provides some reassurance that mild/moderate levels of physical activity in middle age do not increase the risk for ALS but may instead have a beneficial protective effect."
Future research on exercise in ALS, they add, should consider sex differences, capture the most extreme physical activity levels, and identify any genetic factors that may mediate the association between intense exercise and ALS.
No targeted funding was reported. Vaage reported receiving funding from ALS Laboratory Group Norway AS. Other disclosures are noted in the original article.