A new study reveals evidence of a link between physical activity and amyotrophic lateral sclerosis, which supports the idea that a history of vigorous exercise may raise the risk of developing the rare neurological disorder.

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Too much exercise may raise the risk of ALS, particularly in those who are genetically predisposed.

The research, conducted by members of a large European project that is studying amyotrophic lateral sclerosis (ALS), studied subjects in Ireland, Italy, and the Netherlands.

The findings are reported in a paper that is now published in the Journal of Neurology Neurosurgery & Psychiatry.

It is important to note that nowhere in the paper do the authors suggest that the study makes a case for reducing physical activity, or vigorous exercise in particular.

Instead, they note that physical activity has been shown to protect against health problems that are much more common than ALS, including diabetes, several cancers, and cardiovascular disease.

“Decreasing the risk of these common conditions,” the authors propose, “may be a trade-off with increasing the risk of a relatively rare disease such as ALS.”

ALS, otherwise known as Lou Gehrig’s disease, mainly attacks the motor nerve cells, or neurons, that regulate the muscles behind voluntary movements such as walking, talking, and chewing.

The rare disorder affects around 14,000–15,000 people in the United States. It starts as stiffness and weakness in the muscles, but ALS gradually advances to the point where the brain can no longer control voluntary movement and individuals lose the ability to eat, speak, move, and eventually breathe.

The exact cause of ALS, and why it affects some groups of people more than others, is still unknown. However, evidence suggests that both genes and environment are involved.

Several genes have been linked to ALS, with studies indicating that they influence disease risk in different ways — from disrupting cell structure and function to increasing susceptibility to environmental factors.

Studies on the effect of environment on ALS risk have suggested that exposure to toxic chemicals, diet, virus infections, physical trauma, strenuous activity, and other factors may be involved.

The link to physical activity arose from a few small studies of particular cases, the most famous one being that of the celebrated U.S. baseball player Lou Gehrig, which is why the disease also carries his name.

But the evidence linking physical activity to ALS has been inconclusive, and the authors of the new paper suggest that the main reason for this is that studies have been set up differently and use different methods.

For their investigation of the relationship between physical activity and ALS, the scientists analyzed data on subjects who were recruited for a “case-control study” that was conducted by the EURO-MOTOR project.

This project is compiling a “robust and validated computational ALS model” by generating “large-scale quantitative datasets.”

The data came from validated questionnaires filled in by 1,557 adults who had just been diagnosed with ALS, and 2,922 matched individuals without the disease. The participants, who lived in Ireland, Italy, and the Netherlands, were matched by age, sex, and place of residency and were in their 60s.

The responses contained detailed information about: education level; smoking, alcohol, and other lifestyle habits; job history; and their lifetime levels of physical activity at work and during leisure time.

The team converted the physical activity data into “metabolic equivalent of task [MET] scores,” which allow calories consumed to be expressed as a ratio of the amount that is burned when one is just resting.

Using data that each subject gave on the amount of time per week spent in each activity and how many years that activity lasted for, and by referring to a compendium that gives MET scores for different activities, the scientists calculated a physical activity lifetime score for each person.

Analysis for the complete set of cases showed that lifetime physical activity during working hours was linked to a 7 percent raised risk of ALS, and a 6 percent raised risk for leisure time physical activity.

Combining all workplace and leisure physical activities gave an overall increased risk of 6 percent. This link was particularly marked in the subjects who lived in Ireland and Italy.

Using the overall increased risk of 6 percent for all activities translates into a 26 percent higher risk of developing ALS in the subjects who had the highest lifetime MET scores compared with those who had the lowest.

The researchers also found that ALS risk rose in line with increasing lifetime MET scores, which supports the idea that ALS is more common in athletes and professional sportspeople.

The authors point out that because of the observational nature of their study, their findings do not prove that vigorous physical activity actually causes ALS. Other factors, such as a metabolic or energy disorder, or even trauma or diet, “cannot be ruled out.”

In an editorial linked to the study, Prof. Michael Swash — of the Royal London Hospital in the United Kingdom — states that there are “no simple answers” to questions about how environmental factors such as physical activity might impact the development of ALS.

He raises the question of whether or not physical activity might increase the risk of ALS through “excitotoxicity of the central nervous system.”

Excitotoxicity is a type of nerve cell death that has been observed in individuals with ALS. It occurs when the chemical messenger, or neurotransmitter, glutamate over-stimulates neurons.

But Prof. Swash cautions that while it might be “tempting” to imagine that physical activity raises the risk of ALS through excitotoxicity of the central nervous system in susceptible individuals, “any such suggestion is, at present, purely hypothetical.”

Nonetheless, the data are intriguing and deserve closer investigation on a case-by-case basis.”

Prof. Michael Swash