Strenuous exercise increases the risk of motor neurone disease (MND) among people who are already genetically vulnerable, according to a "pioneering" study.
MND describes a group of incurable diseases that affect the nerves in the brain and spinal cord. These nerves ordinarily control muscle function. In MND, the messages sent by the nerves gradually stop reaching the muscles – affecting how a patient walks, talks, eats and even breathes.
Around one in 300 people develop MND at some point in their life, with so-called amyotrophic lateral sclerosis (ALS) being the most common form of the condition.
The late Professor Stephen Hawking was diagnosed with ALS at just 21. In the US, ALS is known as Lou Gehrig's disease, in memory of the New York Yankees baseball player who developed the condition in his thirties.
Exercise has long been linked to MND's onset, however, the association was considered "controversial". To learn more, scientists from the University of Sheffield analysed the genetic information of half a million participants of the UK Biobank study.
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Results link MND to strenuous exercise – defined as working out for over 15 to 30 minutes at a time on more than two to three days a week – but only in people who are genetically at risk of the disease.
Intense workouts can reduce oxygen levels in the body. With nerves among the most oxygen-hungry cells, being deprived of the gas could cause lasting damage.
With there being no way of telling who has this genetic susceptibility, the scientists have urged people to continue exercising regularly for their overall health.
MND's cause is something of a mystery, with genetics and lifestyle factors both thought to play a part.
Studies have suggested professional footballers are up to six times more likely to develop MND. Former footballer Stephen Darby has been diagnosed with the disease, along with rugby players Rob Burrow and Doddie Weir.
Previous research that linked physical activity to MND was of low quality, however.
In the Sheffield study, the scientists used a technique called Mendelian randomisation to turn the Biobank data into an experiment.
Intense exercise was found to change the expression of "many of the 30 plus genes known to predispose to MND".
Around 10% of MND patients are said to have a mutation in the so-called C9ORF72 gene. The Sheffield scientists linked a strenuous lifestyle to early-onset MND in people with this mutation. The disease generally affects people over 50.
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"We have conclusively said exercise is a risk factor for motor neurone disease", study author Dr Johnathan Cooper-Knock told the BBC.
"The numbers of high-profile athletes affected with MND is not a coincidence."
The disease is also more common among military personnel.
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The scientists have stressed most people who exercise vigorously do not develop MND.
"Sport has a large number of health benefits, and most sportsmen and women do not develop MND," said Dr Cooper-Knock.
"The next step is to identify which individuals specifically are at risk of MND if they exercise frequently and intensively, and how much exercise increases that risk".
Experts hope the results, published in the journal EBioMedicine, will boost understanding into MND's cause.
"In recent years, understanding of the genetics of MND has advanced, but there has been little progress in identifying the environmental and lifestyle factors that increase the risk of developing the disease," said Dr Brian Dickie, from the Motor Neurone Disease Association.
"This is, in part, because the genetic and the environmental studies tend to be carried out in isolation by different research teams, so each is only working with part of the jigsaw. The power of this research from the University of Sheffield comes from bringing these pieces of the puzzle together.
"We need more robust research like this to get us to a point where we really understand all the factors involved in MND to help the search for more targeted treatments."
Existing treatments aim to ease a patient's symptoms. Some benefit from physiotherapy or working with a speech and language therapist. Drugs can also slightly slow the disease's progression and relieve muscle stiffness.
Despite the results, official guidance recommends adults be physically active every day, with experts generally stressing the more the better.
Those of a working-age are advised to be moderately active for at least 150 minutes a week, which could include brisk walking, gentle cycling or even pushing a lawn mower.
If time-pressed, being vigorously active for 75 minutes is advised via jogging, cycling briskly or skipping rope.
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