Posted February 26, 2021

Pavan Bhargava, M.D., Johns Hopkins University

Dr. Pavan Bhargava

Current pharmacological therapies do not significantly improve multiple sclerosis (MS) symptoms, such as weakness, fatigue, or mood disturbance, however, studies indicate exercise training can improve these MS symptoms. Exercise alters multiple metabolic pathways, which may contribute to its beneficial effects. “Global untargeted metabolomics” is a technique that involves the measurement of multiple metabolites in plasma or serum. Metabolomics analyses have previously identified differences in the metabolome between people with MS (pwMS) and healthy controls.

With support from a Fiscal Year 2016 Exploration - Hypothesis Development Award (EHDA), Dr. Bhargava and his team studied the metabolic changes from exercise in pwMS. The researchers hypothesized that exercise may alter the metabolome and these changes may mediate beneficial effects on MS symptoms. Utilizing metabolomics they studied alterations in the metabolome and the relationship to changes in MS-related symptoms. Specifically, they studied the impact of a 12-week physical therapist-supervised Progressive Resistance Training (PRT) intervention on hip strength (using dynamometry), walking (using a 6-minute walk test [6MWT] and a timed 25-foot walk [T25FW]), fatigue (using a Modified Fatigue Impact Score [MFIS] assessment), and physical activity (using the Godin leisure-time physical activity scale [GLPAS]). In MS participants the PRT intervention led to increases in hip strength, distance walked during 6MWT, increased walking speed on T25FW, reduced fatigue based on MFIS scores, and increased activity based on GLPAS. They identified 51 metabolites that changed in pwMS following the intervention, while there was no significant change in the metabolome in healthy controls. They observed a significant relationship between sex steroid (such as dehydroepiandrosterone sulfate [DHEAS]) metabolism changes and fatigue scores as well as a relationship between fatty acid metabolism and cardiovascular fitness (as measured by maximum rate of oxygen consumption) in pwMS.

These relationships are of interest because they could provide insight into the mechanisms by which exercise improves MS-related fatigue and other disability measures. Indeed, several studies have identified relationships between levels of sex steroids and fatigue in other disorders; hence, the relationship observed here between the change in sex steroid metabolism and fatigue scores is not surprising. Additionally, identification of metabolic pathways that are associated with symptomatic benefits could lead to the development of alternative treatment strategies, both pharmacologic (such as supplementation of sex steroid like DHEA) and neurorehabilitative, for targeting these pathways.

Link:

Public and Technical Abstracts: Evaluating the Metabolic Changes Associated with Exercise in Multiple Sclerosis

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