Are Intense exercises a cause of ALS?

Lou Gehrig was an outstanding baseball player and led the New York Yankees into six World Series victories. He was only in his thirties when he was diagnosed in 1939 with amyotrophic lateral sclerosis (ALS). Amyotrophic lateral sclerosis is a disease that causes motor neurons to deteriorate. It eventually results in the loss of muscle movement, eating, speaking, breathing, and other functions. Gehrig's sickness, already well-documented for many years, was brought to the attention of people long before the first Baseman died in 1941. The condition became so common that the name "Lou Gehrig’s Disease" was adopted.

Professional athletes, such as Gehrig, have been known to succumb to ALS. For example, reports have indicated that ALS rates are higher in Italy than the average for professional soccer players. Scientists also discovered similar rates in American National Football League athletes. Many scientists have wondered if elite sport or intense exercise might increase your risk for developing neurodegenerative diseases.

Despite the many studies that have examined whether physical activity is tied to ALS, researchers have yet to pinpoint a clear answer. While some studies have shown a connection, others do not. Researchers have begun to investigate whether there are other factors that could explain the conflicting results, like metabolism and genetic predisposition. Valentina Gallo from the University of Groningen, Netherlands, says that the evidence suggests there may be something more to this relationship than just physical activity.

Too Much Movement

It has been suggested that ALS may be linked to physical activity for decades. MacDonald Critchley (a British neurologist) pointed out Gehrig's case at a 1962 conference. He also noted that Gehrig was an athlete who might have contributed to ALS. Critchley stated that nothing has been done to determine if an athlete's past habit could have played a role in the aetiology. I have the uneasy feeling that motor neurone diseases may develop in later years due to a history of excessive muscular movements, which was not apparent.

Many investigators tried to determine if this belief was true over the following years. Some studies-such as those of Italian soccer players or American football players-suggested that there was, indeed, something about high levels of exercise that increased the risk of the illness. Some jobs, such as farming or metalworking, that require a lot of physical labor could raise the chance that ALS will be diagnosed. Other studies, however, failed to find a heightened risk of ALS in individuals who had some of those occupations-or among people who, in general, had a very active lifestyle. Elisa Longinetti (postdoctoral researcher, Karolinska Institute, Sweden) says, "Physical activities are a difficult exposure to assess in terms if intensity and duration." "That's why I think we've found so many conflicting results in several studies investigating its effect on ALS."

This research presents a challenge in determining the best way to determine the amount of exercise a person has been exposed to over their lifetime. In a study published on October 20 in Neurology, Angela Rosenbohm, a neurologist at Ulm University in Germany, and her colleagues tried to get a better estimate of people's lifetime physical activity by asking them very specific questions about the types of activities they engaged in during work and leisure and how those activities changed across different life stages.

This team was drawn from a huge database of all newly diagnosed ALS cases in Swabia. Swabia is a southwestern part of Germany. The researchers selected two healthy volunteers randomly from the population to enroll each patient. The researchers ended up with 791 healthy recruits and 393 patients with ALS. The participants were required to provide information about their physical activity at the ages of 20, 30, 40 and 50, as well as how long and intense they did it (e.g. whether the activity was work related or if they broke out in sweat ).

This study revealed that physical activity and ALS may be connected in a more complex way than previously considered. Only those who were physically active in their jobs, and not through leisure, had an elevated risk of developing ALS. Rosenbohm says that rather than being a consequence of physical activity, this link may arise from other underlying factors, such as higher levels of toxins or pollutants in workplaces where the most physically demanding jobs take place-which would be consistent with what has been reported in other studies. She adds that professional athletes (who were not explicitly examined in this study) may be exposed to pesticides on the field.

Rosenbohm and his team discovered that there wasn't a correlation between exercise and risk for ALS. However, the latter was associated with the eventuality of the condition. People who are very active were less likely to succumb to ALS than those who are more active. The data also shows that moderate exercise may be beneficial for people living with ALS, both after they are diagnosed and when their symptoms begin.

The researchers also discovered that, around five to 10 years before they were diagnosed, many patients with ALS reported a steep drop in their physical activity, which was much more pronounced than that seen in healthy individuals-suggesting that the disease may cause changes in the body that start many years before the deterioration of motor neurons begins.

Rosenbohm’s study has one limitation, as many other studies before it: participants must provide self-reports. Gallo explains it's difficult for those with movement-related diseases, such as ALS to recall past activity in an impartial manner. Gallo says that the only way to remove bias is to record physical activity in prospective cohort studies, which are long-term observation of a larger group. If a group is kept for long enough, it's possible to diagnose ALS in some of the participants. But these resource- and time-intensive studies are few and far between.

In 2016 Gallo and her colleagues conducted such a study of ALS using data on 472,100 people from 10 different European countries that had been collected between 1992 and 2002 for a long-term investigation on cancer and nutrition. Each subject completed a questionnaire regarding their exercise habits, at work or in leisure. There was also information available on the causes and deaths of these subjects. By the time this study took place, 219 of these individuals had died from ALS. The team found that, contrary to the many retrospective studies on the topic, being active appeared to very slightly decrease-rather than increase-the risk of dying from the disease.

Other explanations

Studies suggest that there may also be other explanations for the link between intense physical activity and ALS.

While exercise may not increase the likelihood of ALS, it could make the condition worse for those who are predisposed. In a study published in EBioMedicine this spring, researchers reported that higher levels of past physical activity were associated with earlier disease onset only in patients with a mutation in the C9ORF72 gene-the most common cause of inherited ALS. They also found exercise alters the production of the C9ORF72 protein gene. The authors of the paper say that their findings may explain the inconclusive effects of exercise reported in prior studies, most of which did not examine the role of genes.

A second hypothesis states that the true culprit is not exercise, but rather how people use their metabolism. Research has shown, for instance, that people with a higher body weight index are less likely than others to contract ALS. Also, losing weight can accelerate the process.

Alberto Ascherio is a Harvard University neuroepidemiologist. He says, "It appears that people with ALS have a kind of accelerated metabolism." Ascherio, along with his collaborators, discovered abnormal metabolic signs in blood samples from individuals who had ALS many years prior to their diagnosis. This suggests that something is happening in patients long before their symptoms appear-which is consistent with the reduction in physical activity that Rosenbohm's team observed in its latest study, Ascherio adds. He says, "Whatever that means, we're still not able to pinpoint it."

However, it remains to be determined if altered metabolism is the cause or effect of the illness. Gallo states that there is a lot of evidence to show that patients suffering from ALS have a higher metabolism. However, most of these cases are already diagnosed with the disease so it is difficult to determine if the increased metabolism was a result of the disease.

Ascherio states that there is no clear connection between high levels of physical activity and an increased chance of developing ALS. Therefore, it is difficult to recommend a specific level or intensity for people who want to avoid the disease.

ALS can be a very rare condition. As a result, even if you do not want to exercise as much, regular exercise may help keep your body from developing other diseases such strokes, cardiovascular disease and dementia. He says, "Remain active."