Metabolic Changes May Indicate Improved Clinical Outcomes in Multiple Sclerosis

Progressive resistance training was shown to positively alter several measures of disease progression in the study cohort: fatty acid, phospholipid, and sex steroid metabolism.

Compared with controls, fatty acid, phospholipid, and sex steroid metabolism underwent substantial changes among persons living with multiple sclerosis (pwMS) following progressive resistance training (PRT), according to findings published in Annals of Clinical and Translational Neurology.

The study cohort, all of whom had relapsing-remitting MS, and healthy controls (N = 27) were matched 1:1 based on age and sex, with an average Expanded Disability Status Scale (EDSS) score at baseline of less than 4 and no comorbid medical conditions preventing exercise among the pwMS. The mean (SD) patient age was 42 (13) years in the MS cohort and 39 (14) in the health controls.

Phlebotomy and EDSS were performed at the baseline and end-of-study visits

“The benefits of exercise extend beyond symptomatic improvements,” the authors wrote. “However, the degree to which an individual with MS responds to exercise can vary widely. We sought to determine the effects of a PRT exercise program on the metabolome of pwMS.”

Their primary outcomes were increased strength, mobility, and fatigue as measured by plasma metabolomics analysis, cardiovascular fitness tests, EDSS, timed 25-foot walk (T25FW), 6-minute walk test (6MWT), hip strength, and modified fatigue impact scale (MFIS).

Overall, both groups experienced gains in hip strength, distance in the 6MWT, and walking speed following PRT, which comprised 12 weeks of hip strengthening, at 3 sessions per week, for a minimum of 33 sessions.

However, the study group experienced 2 additional outcomes vs the control group: the aforementioned changes in fatty acid, phospholipid, and sex steroid metabolism and improved fatigue levels. The latter was strong inversely correlated with changes in sex steroid metabolite module in pwMS and dehydroepiandrosterone sulfate (a sex steroid metabolite) abundance.

Conversely, there was a greater likelihood of an inverse relationship between fatty acid metabolism and cardiovascular fitness in the study group.

Analyses also resulted in these outcomes:

  • Nonuniform improvements in hip strength among the pwMS, with just 57% (n = 8) seeing meaningful increases above the minimal detectable change reference of 5.1 lb.
  • Compared with nonresponders in the pwMS, those who responded to the PRT had significant mean cardiovascular endurance changes in the following:
    • 6MWT: 31 (35) vs 20 (32) m
    • T25FW: –0.41 (0.4) vs –0.17 (0.29) s
    • MFIS total: –13 (5) vs –2 (5)
    • MFIS physical: –7 (4) vs –0.5 (1)

The authors noted that their findings add to the literature on the benefits of exercise among pwMS and “are compatible with those seen in prior studies of exercise interventions in other populations.”

In addition, the effects of the PRT on the metabolome and how that influenced the changes in strength, endurance, and fatigue could indicate a beneficial effect on clinical outcomes, such as on fatigue and hip strength. Specifically because some metabolic changes differed in the pwMS when looking at responders vs nonresponders.

“PRT-induced metabolic changes may underlie improved clinical parameters in pwMS,” the authors concluded, “and may warrant investigation as potential therapeutic targets in future studies. This will also provide rationale to investigate sex steroid supplementation to treat MS-related fatigue and augment response to exercise interventions.”


Keller J, Zackowski K, Kim S, et al. Exercise leads to metabolic changes associated with improved strength and fatigue in people with MS. Ann Clin Transl Neurol. Published online May 6, 2021. doi:10.1002/acn3.51368

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