Playing Professional Soccer Linked to Increased ALS Risk

Pauline Anderson

March 04, 2019

Compared to the general population, professional soccer players have a twofold increased risk for amyotrophic lateral sclerosis (ALS), and they appear to develop the condition some 20 years earlier, preliminary results of a new study suggest.

Dr Ettore Beghi

The results strengthen the argument that environmental factors contribute to ALS, lead author Ettore Beghi, MD, head of the neurological disorders laboratory, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy, who is a fellow of both the American and European Academies of Neurology, told Medscape Medical News.

The study findings should spur physicians to "warn patients to prevent head injuries," said Beghi.

The study will be presented at the upcoming American Academy of Neurology (AAN) 2019 Annual Meeting.

Soccer Cards

The association between ALS and soccer has been attracting attention since a number of Italian soccer players died from the condition. The role that this and other environmental or genetic factors play in the development of ALS has not been determined.

For this new study, Beghi and other researchers tapped into the archives of a publisher of popular collectible trading cards featuring Italian soccer players. They identified all professional soccer players from 1959 to 2000.

They recorded the date, place of birth, and team position for each of the 23,875 players that were included.

To uncover cases of ALS, the researchers used multiple sources, including newspapers, the Internet, and scientific reports.

The investigators calculated the incidence rate (number of cases per 100,000 person-years) in the soccer cohort and used a well-defined Italian registry to determine the expected rate in the general population.

They also calculated the standardized incidence ratio (SIR), the observed vs expected incidence of ALS, within different age groups.

The researchers identified 33 players who developed ALS (3.2 cases per 100,000 per year). The number of expected cases was 17.6 (1.7 cases per 100,000 per year).

The SIR was 1.9 (95% confidence interval [CI], 1.3 – 2.6) in the soccer sample. However, the SIR was 4.7 (95% CI, 2.7 – 7.5) in those who were younger than 45 years at the time of their diagnosis.

The median age at ALS diagnosis among players was 43.3 years compared to 62.5 years in the general population.

"When stratifying the data according age groups, we found an almost fivefold increased risk of ALS among former soccer players, when focusing the analysis on people who were diagnosed with the disease before age 45," said Beghi. "This means that former soccer players tend to get ALS at a significantly younger age compared to the rest of the population."

Repeated head trauma could be the link between soccer and ALS. Beghi and his research team have already shown that people with ALS report a history of head injuries more often than those without ALS.

Professional soccer players are also extremely physically active. Some published reports support the association between physical activity and ALS, said Beghi.

"Soccer players also use nonsteroidal anti-inflammatory drugs and perhaps also dietary supplements, and both of these have been implicated in the mechanisms of the disease," he said.

Beghi stressed that it's possible that these factors play a role only in genetically predisposed individuals.

The researchers also assessed the effect of player position and found that more midfielders developed ALS compared to forwards, defenders, or goalies. The midfielder position is the predominant position on a soccer team, so this finding is not that meaningful, said Beghi.

The researchers didn't have information on the level of field activity, but they did know the years in which the players started their career. "The increased risk was significant for people playing before 1965 and between 1975 and 1984," said Beghi. "At present, there is no reasonable interpretation of these findings."

The researchers now plan to study the occurrence of dementia and Parkinson disease in former soccer players, said Beghi.

Novel Design

Asked to comment on the study, Stephen Goutman, MD, director, Multidisciplinary ALS Clinic, and associate professor of neurology, the University of Michigan, Ann Arbor, noted its "fairly novel" design.

The study builds on the observed heightened ALS risk among Italian soccer players "in a very systematic way" by using soccer cards and tracking every player over time to determine whether they developed ALS, said Goutman. "This is something we haven't really seen before in ALS," he noted.

Goutman said he'd like to know what's behind the earlier ALS diagnosis among soccer players in the study. He noted that the researchers did not know the genetic history of players and had no biological samples or DNA to evaluate.

"Is it that they're so physically active and burning out their motor neurons earlier in life, or is it some other factor that we're not accounting for?" he asked.

Goutman elaborated on the two main explanations for why playing soccer at a professional level increases the risk for ALS.

Tipping Point

The first is exposure to rigorous physical activity, which has been shown to slightly increase ALS risk. "There seems to be some tipping point where too much physical activity heightens the ALS risk," said Goutman.

But the mechanism linking rigorous but not moderate activity is unclear. "We don't know what causes that switch — from something that's moderate and doesn't seem to increase the danger to your motor neurons to something more severe," he said.

Goutman stressed that the cardiovascular benefits of participating in physical activity outweigh the risk for ALS.

The second explanation — the head trauma hypothesis — has received a lot of research interest lately, said Goutman

But other factors are also tied to increased ALS risk, including exposure to chemicals, such as fertilizers. Some occupations, for example, working on electrical lines, appear to be associated with a higher incidence of ALS.

Members of the US armed forces, too, appear to be at increased risk, possibly because of the required physical activity or the head trauma or chemicals they may have been exposed to in combat, said Goutman.

ALS researchers are intent on firmly identifying the triggers driving ALS susceptibility, he said.

"There's a lot of good evidence out there showing these associations, and we need to continue to find these associations, but we also need to start connecting the dots so we can go from association to causality," he said.

If researchers can make these mechanistic connections, it might open the door for intervention opportunities, said Goutman. For example, if extreme physical exertion is positively linked to ALS, then people with an underlying genetic ALS risk might be counseled against intensive exercise.

Beghi and Goutman report no relevant conflicts of interest.

American Academy of Neurology (AAN) 2019 Annual Meeting.

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