Case-Control Study Highlights Significant Negative Effects of Obesity in Patients With Multiple Sclerosis

Anna Karin Hedström, MD, PhD

A recently published population-based case-control study showed that patients with multiple sclerosis (MS) who were obese had higher disease activity, worse health-related quality of life, and lower cognitive function. In the study, both being overweight and obesity were linked to increased MRI activity, while obesity was associated with poorer general health, greater fatigue, and higher levels of pain.¹

The Swedish study featured 3249 patients with MS, of whom 70% were women, who were evaluated on changes in Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale 29 (MSIS), and Symbol Digit Modalities Test (SDMT). Led by Anna Karin Hedström, MD, PhD, a senior specialist in the department of Clinical Neuroscience at Karolinska Institute, the study’s mean follow-up time was 10.6 years (SD, 6.1), with participants recruited from April 2005 to December 2019.

At baseline, the mean age of participants was 37.8 years, and the mean duration since the onset of disease was 3.2 years. Using a linear mixed model, results showed that patients who were obese (n = 474) had a 0.2-point faster annual increase in their EDSS score (ß for EDSS score x time, 0.02, 95% CI, 0.00-0.04) and a faster annual decrease in the SDMT score (ß for SDMT x time, –0.19; 95% CI, –0.38 to –0.01) in comparison with those considered a healthy weight (n = 1842; 18.5-24.99 kg/m²). For context, overweight was considered 25-30 kg/m² while obese was anything greater than 30 kg/m².

"How obesity may affect disease progression and cognitive functioning in MS is not well understood; however, several hypothesized interrelated mechanisms have been identified," Hedström et al commented. "Obesity induces a state of chronic low-grade systemic inflammation and local inflammation in the brain, which may contribute to neurodegeneration and cognitive decline. Epigenetic modifications induced by obesity may also adversely affect disability and progression in MS."

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Compared with healthy weight, being overweight was not significantly associated with EDSS-related outcomes while obesity was associated with a greater risk of reaching EDSS score 3 (adjusted HR, 1.43; 95% CI, 1.17-1.75) and EDSS score 4 (adjusted HR, 1.40; 95% CI, 1.07-1.73). In a subgroup analysis of obese patients, those with a BMI between 30 and 35 had a 1.35-fold (95% CI, 1.06-1.72) risk of reaching EDSS score 3 whereas those with a BMI above 35 had a 1.59-fold (95% CI, 1.17-2.17) increased risk. The corresponding HRs for reaching EDSS score 4 were 1.39 (95% CI 1.00–1.98) and 1.69 (1.15–2.80), respectively.

Obese participants faced a higher risk of physical (HR, 1.42, 95% CI 1.19–1.69) and psychological worsening (HR, 1.23, 95% CI 1.05–1.46). However, no significant differences were observed among BMI groups in cognitive disability progression, as measured by changes in the SDMT score. Both overweight and obesity were linked to an increased risk of developing new MRI lesions, with adjusted HRs of 1.21 (95% CI, 1.02–1.44) and 1.29 (95% CI, 1.03–1.62), respectively.

When the analysis was stratified by treatment regimen, obesity remained significantly associated with disability progression in both groups. Restricting the analysis to participants who maintained the same BMI category during follow-up revealed stronger associations between obesity and unfavorable outcomes, with an HR of 1.51 (95% CI, 1.09–2.09) for cognitive disability worsening, as measured by the SDMT, among obese participants compared to those without obesity.

In the study, subgroup analyses of patients who lost weight were limited by small sample sizes and lacked details on whether weight loss was intentional, surgery-related, or due to disease. The timing of weight loss was also unclear, which is crucial since its effects on progression may take time to manifest. Additionally, early-life obesity may have lasting effects on MS progression, complicating conclusions about the benefits of later weight loss. Investigators concluded that further research is needed to clarify these relationships.

REFERENCE
1. Wu J, Alfredsson L, Olsson T, et al. Obesity Affects Disease Activity and Progression, Cognitive Functioning, and Quality of Life in People With Multiple Sclerosis. Neurology. 2025;12(1). doi:10.1212/NXI.0000000000200334