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Clinical Challenges: Obesity and MS

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Clinical Challenges: Obesity and MS

Despite the recognition that we are in the midst of a worldwide obesity epidemic, obesity rates continue to increase. And a failure to come to grips with this epidemic is having deleterious impact when it comes to multiple sclerosis.

Not only is there evidence that obesity may contribute to the incidence of MS, but it may also worsen MS in persons who already have the disease.

In a 2018 study, Canadian researchers found that elevated body mass index (BMI) is strongly associated with an increased risk of MS, where a one standard deviation increase in BMI resulted in a 41% increase in the risk of MS. From a clinical perspective, that 41% increase corresponds to a change in BMI category from overweight (BMI ≥25) to obese (≥30), per World Health Organization guidelines, the team wrote, adding: “This suggests that childhood and early-adulthood BMI is an important modifiable risk factor for MS.”

The association between obesity and MS seems particularly salient when it comes to children and teens. A 2019 German study found that children and teens who were overweight or obese had twice the risk of developing MS than non-overweight children did. And when those researchers compared responses to MS treatment with interferon beta or glatiramer acetate, they found that obese children had significantly more relapses on treatment and were more likely to have switched to second-line treatment.

“Additional research is needed to understand this association,” the investigators concluded. “It is important to note that not everyone who is obese during adolescence will develop MS, and also that many people develop MS without having been obese during adolescence.”

“While our study results indicate that obesity in childhood is associated with an increased risk to develop MS, the study did not examine the causes for this association,” the study’s senior author, Peter Huppke, MD, of Georg August University in Göttingen, told MedPage Today. “One could speculate that adipose tissue has proinflammatory effects, thereby promoting the development of MS. However, it is also possible that genetic or environmental factors, including diet, can promote both MS and obesity.”

Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba, agreed that adiposity promotes inflammation, which could influence MS, and that diet and a lack of physical activity could play a role as well.

“We also know that obesity influences your vitamin D levels,” Marrie told MedPage Today. For example, in a recent Mendelian randomization study, researchers not only provided evidence that BMI before the age of 10 is an independent causal risk factor for MS, but also suggested that low levels of vitamin D play a causal role in the pathogenesis of MS.

Whatever the association, the impact of obesity on MS patients appears to be substantial: “One of the hallmarks of MS is the risk of relapse,” said Marrie, who pointed out that a recent study by Australian researchers found that among MS patients the relative risk of relapse goes up as BMI increases. That study found that higher BMI was associated with a greater risk of relapse, as well as a higher rate of disability progression.

“This is consistent with other work that shows that people with high BMI have a greater decline in Expanded Disability Status Scale scores, which focuses heavily on ambulation, and a greater decline in walking speed over time,” said Marrie. “And we know with imaging studies that people with MS have brain volume loss over time that is greater than people without MS, and that those persons who are obese have greater volume loss over time.”

This association between obesity and MS leads to the question: Can treating this comorbidity improve the course of the disease?

“We don’t know the answer to that question, although it is an important one,” she said, adding, though, that there are some diet-related studies that suggest that individuals who alter their diet can have improvements in MS-related fatigue. “But there has been nothing specifically aimed at normalizing body mass index as a specific therapy for MS,” she said.

One difficulty in approaching this association between obesity and MS is that there are many potential reasons persons with MS may find it difficult to achieve a healthier weight.

“These are persons who are likely to be less physically active, which may be due to a combination of factors,” Marrie explained. “They may have weakness and other physical limitations, and they may not be walking, or are finding it harder to walk under those circumstances. And people can suffer significantly from fatigue, even early in the disease course, and even when they don’t have physical impairment, that can limit a person’s ability to exercise as well. Persons with MS are also taking medications to manage their MS symptoms and this may increase their appetite and contribute to weight gain.”

Marrie said it is important to educate MS patients as soon as they are diagnosed about the role obesity and related health conditions can play in their outcomes: “The international brain health guidelines also talk about the importance of addressing a brain-healthy lifestyle in patients with MS at each clinic visit,” she added. “In our practice we are fortunate enough to have a dietitian who can meet with patients and review what they are currently doing and provide some input about changes they can make and provide support on an ongoing basis.”

As for where research should focus on in this area, Marrie suggested that it is important to understand how obesity — and other health conditions closely related to obesity, such as high blood pressure, high cholesterol, and diabetes — can influence responses to disease-modifying therapies.

“It would be very important to study the pharmacokinetics of MS medications in obese MS patients,” Huppke added. “It is likely they do not receive the appropriate dosage. Moreover, research should address the basic question: why is there an association between obesity and MS? The answer to this question might help us to prevent the development of MS in the future.”

Disclosures

Huppke reported financial relationships with Bayer Health Care, Merck Serono, and Novartis.

Marrie reported research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC and the U.S. Department of Defense, and support from the Waugh Family Chair in Multiple Sclerosis.

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