Research on Exercise’s Protective Effects Flawed, Researchers Say

Recent clinical trials are too short, unfocused, and use 'poorly defined cohorts'

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An international team of scientists is calling for more rigorous studies to test whether exercise can help protect the nervous system from damage in people with multiple sclerosis (MS).

The scientists argue clinical trials that have evaluated exercise in MS have marked flaws in their design, making it impossible to draw meaningful conclusions from available data.

“The shortcomings of existing research preclude the rendering of strong conclusions at this time,” Brian Sandroff, PhD, a study co-author and director of the exercise neurorehabilitation research laboratory at Kessler Foundation, said in a news release from the foundation.

“As an approach that offers low cost, easy access, and few side effects, the potential benefits of exercise for individuals with multiple sclerosis warrant thorough investigation,” Sandroff added. “Only through rigorous study can we explore the promise of neuroprotection for individuals living with multiple sclerosis.”

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The team’s correspondence article, titled, “Exercise training in multiple sclerosis,” was published in The Lancet Neurology.

Preclinical research has suggested physical exercise has neuroprotective effects, helping to shield the nervous system from damage. Thus, several clinical trials have been conducted to explore these potential neuroprotective effects of exercise for people with MS.

Two review papers, both published last year, assessed available data from these trials and found no evidence that exercise was neuroprotective. Here, scientists argue these findings do not necessarily mean that exercise doesn’t have neuroprotective effects.

“We argue that the absence of evidence does not constitute evidence of absence,” the research team wrote.

The researchers noted a number of limitations among available clinical trials, including the fact that their duration, which typically ranged from one to six months, was probably too short to identify any neuroprotective effect.

According to the team, even potent disease-modifying medications, which are proven to slow the disease’s progression, do not typically have a clear neuroprotective effect after only six months.

The trials also included patients with relatively early disease without a lot of ongoing inflammatory brain damage. This isn’t conducive to studying neuroprotection, since by definition there needs to be a fair amount of ongoing damage for a protective effect to become clear.

Furthermore, many of the approaches being used in trials are inconsistent with how exercise is thought to affect neuroprotection. This includes the exercise regimens applied, as well as the relatively broad measures used to monitor changes in brain composition.

While most studies relied on whole-brain measures, studies in other conditions suggest that the effects of exercise are focal, affecting specific brain regions that need to be examined in more detail.

The team said approaches used are “analogous to conducting a regulatory disease modifying therapy trial without incorporating preclinical research.”

“Researchers should carefully evaluate the evidence when making sweeping inferences that can stall a field of inquiry; this field will not advance with studies that collectively include short-term and generalised exercise, poorly defined multiple sclerosis cohorts, and exploratory, whole-brain neuroimaging endpoints over short time periods,” the scientists said.

“Advancing this line of research depends upon well-designed, randomized, controlled trials based on our knowledge of focal, exercise-induced neuroprotection, with targeted selection criteria, adequate durations of training and follow up, and appropriate neuroimaging techniques,” Sandroff said. “That will comprise the future evidence base for assessing the role of exercise training in the management of multiple sclerosis.”

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