Regular strenuous sport and exercise can help cause the fatal neurological disease ALS, according to a new study – but don’t go skipping leg day.
ALS, which stands for amyotrophic lateral sclerosis, is the most common type of motor neurone disease, a group of rare and relatively mysterious conditions that affect the brain and nerves. It is irreversible, progressive, and fatal, and although incredible advances in treatment have been made in recent years, there is still no cure, no “standard” progression, and until now, no definitive known causes.
In recent years, the most famous person to develop ALS was the legendary physicist Stephen Hawking, who embodied the unpredictable nature of the disease by living for five decades longer than expected at diagnosis. But the most famous person before that – and the patient whose name is now indelibly tied to the disease – was Lou Gehrig, major league baseball player for the New York Yankees who died aged just 37.
But Gehrig was far from the only professional sportsperson to develop the disease. Professional soccer players are more than six times as likely as the general population to suffer from ALS, according to studies, and even competing in varsity sports has been correlated to an increased risk. But until now, this link was just that: a correlation, rather than a cause.
"We suspected that exercise was a risk factor for ALS but until now this was controversial," Dr Johnathan Cooper-Knock, an author of the new study, explained in an email to IFLScience. "There were questions over whether exercise may simply reduce risk of death from other causes (e.g. cardiovascular disease) which could indirectly make people more likely to die from [motor neurone disease]."
That’s where the new research has an advantage – two, actually. First of all, the team used a technique called Mendelian randomization. Unlike a traditional population sample, this technique measures the prevalence of certain conditions or attributes based on measurable genetic differences, and that means that much of the “noise” of confounding variables can be filtered out. In this case, the researchers measured ALS prevalence in the population stratified by a genetic predisposition towards exercise.
Secondly, the researchers had access to the UK Biobank, a huge repository of genetic and lifestyle information that has previously been instrumental in everything from the COVID-19 pandemic to gay rights.
The study, which was published in the journal EBioMedicine, explains how lifestyle factors such as smoking, educational attainment, and body fat percentage, which have previously been suggested as possibly affecting ALS risk, were ruled out. Instead, the researchers discovered exercise – specifically, regular, strenuous exercise – to be the main culprit.
“Exercise is not one homogeneous exposure,” the paper clarifies. “Different types of exercise can impact different biological pathways and even different subtypes of motor neurons. … Consistent with this, our MR study does not support a causal role for low-intensity, infrequent exercise, but does support toxicity resulting from high-intensity, frequent, leisure-time exercise.”
To examine their hypothesis closer, the researchers took a look at over 300 genes that are known to be affected by intense exercise. They found that more than one in five of them were associated with an increased risk of developing ALS, and some are known to directly cause motor neurone death in lab conditions.
But although the evidence is convincing, the researchers are clear that we shouldn’t hand in our gym membership because of it.
"[We have established] that frequent strenuous exercise has a causal link to ALS," Cooper-Knock explained to IFLS. "However, we do not know which individuals are at risk of exercise-induced ALS. Clearly exercise is extremely beneficial for most people and therefore we are not advising anyone to reduce their exercise currently."
"Most people who exercise a lot will NOT get ALS," he continued. "Our future aim is to ... offer these at-risk individuals counselling about their exercise habits to allow them to make informed decisions."