Body mass index may play a role in MS progression

April 15, 2019
A new study suggests a link between blood lipids and worsening of disease in multiple sclerosis patients who are overweight and obese. The findings support the concept of nutri-epigenomics (the ability of food to modify the way genomic information is interpreted by each cell) and the idea that lifestyle factors such as diet and weight can function as disease modifiers.

The longitudinal investigation, conducted by researchers at the Advanced Science Research Center at the Graduate Center of the City University of New York's Neuroscience Initiative in collaboration with clinicians at the Icahn School of Medicine at Mount Sinai, followed recently diagnosed MS patients for two years. The researchers found that individuals who were overweight or obese had higher levels of blood lipids called ceramides, which placed markers on the DNA of monocytes, making them proliferate. Monocytes are blood cells that can travel to the brain and damage nerve fibers. Two years into their diagnosis, study participants with higher levels of ceramides and monocytes also had greater loss of motor skills and more brain injury.

Two cohorts of patients – a primary one and a validation group – were recruited from the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai and the National Institutes of Health to participate in the study. For the first group, 54 therapy-naïve MS patients 18 to 60 years old with high or normal body mass indexes were evaluated using brain MRI to identify signs of brain damage; a clinical assessment to ascertain weight, disabilities, and other vital information; and blood tests to analyze the types of circulating lipids and white blood cells. An independent validation group of 91 MS patients from the National Institute of Health with the same characteristics and additional control cohorts of healthy individuals within the same BMI range were similarly evaluated.

Researchers found that MS patients with high BMIs had higher ceramide levels and more circulating monocytes than were evident in healthy individuals with the same BMIs. High-BMI MS patients showed worsening disability and more brain lesions at the MRI compared to their normal BMI counterparts. The researchers went on to find that ceramides can enter inside immune cells called monocytes and change the way these cells read the genetic information encoded in the DNA. These epigenetic changes were also found in monocytes circulating in the blood of MS patients with high BMI.

The detection of ceramides inside the nucleus of blood cells and the ability of these lipids to induce epigenetic changes suggests that saturated fatty acids may have long-lasting functional effects, which over time steer the MS disease course towards worsening disability. In short, bad dietary habits may have negative consequences in healthy subjects, but they have an even more pronounced deleterious effect on patients with MS because the degrading myelin can accumulate and further increase ceramide levels.

Further study is needed to determine whether specific dietary interventions and weight management could be useful in helping MS patients manage and slow the progression of their disease and better respond to disease-modifying treatments.

The paper was published in the Lancet journal EBioMedicine.

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