Childhood Obesity Linked to Higher Risk of Multiple Sclerosis, Possibly by Altering Vitamin D Levels

Obese children and young adults appear to be at a considerably higher risk of developing multiple sclerosis (MS), according to researchers at the McGill University in Canada and collaborators at the University of Bristol in the U.K., who found a causal relationship between the two.

Their study, “Obesity and Multiple Sclerosis: A Mendelian Randomization,” published in the journal PLOS Medicine.

Several observational studies suggest that obesity, as measured by body mass index (BMI),  in a person’s younger years is associated with an increased risk of MS. One, called the Nurses’s Health Study, enrolled 238,371 women with a BMI of 30 or more at age 18 and associated obesity with a 2.25-fold increase in MS  risk, suggesting that obesity may be involved in disease development by promoting a proinflammatory state.

Despite such findings, most MS studies do not take into account lifestyle factors that influence BMI, opening such research to misinterpretation of results and leaving the possible connection between a high BMI and MS undeveloped. Now, researchers revealed that obesity is causally associated with MS, meaning it can cause disease onset, making efforts to control a young person’s weight even more important that previously thought. They also suggest that vitamin D levels, which are thought to decrease as a person’s weight increases, may be a mechanism behind this association.

To establish the causal relationship between high BMI and MS, researchers tested whether genetic variations influencing BMI are also associated with MS. This allowed the team to provide an estimate that was not influenced by confounding factors.

Researchers examined data from two large studies analyzing such genetic variations. One, the Genetic Investigation of Anthropometric Traits (GIANT) consortium, included 322,105 people and assessed BMI and genetic variants; the other, the International MS Genetics Consortium (IMSGC), studied genetic variations in 14,498 MS patients and compared them with 24,091 controls.

Re-analysis of GIANT found that 70 single nucleotide polymorphisms (SNP, or mutations where one nucleotide in the DNA is changed by another) were significantly associated with higher BMI. These SNPs were then examined for their association with MS risk in the IMSGC study’s subjects.

Findings here demonstrated that genetically elevated BMI is strongly associated with an increased risk of MS. Particularly, a 4.7 increase in BMI increased by 41 percent the odds of developing MS. A genetically determined change in BMI, from overweight to obese, was also associated with a substantially increased risk of MS.

But genetic determinants of MS do not contribute to BMI, the research team said their findings suggested.

These results indicated that BMI is an important and, importantly, a modifiable risk factor for MS in childhood and early adulthood. They also carry significant public health implications, because of the prevalence of childhood and adolescent obesity in many countries today. Controlling obesity may be a means to prevent MS onset or its progression.

Further study is needed, researchers said, particularly into what triggers the association found — like how weight affects vitamin D levels in the body. “Current evidence suggests that there are several potential mechanisms through which increased BMI may affect MS risk; however, it remains unclear which of these pathways are critical,” they wrote. “Vitamin D is a strong candidate, given that previous MR [Mendelian randomization] analyses demonstrate that genetically elevated BMI decreases 25-hydroxyvitamin D levels.”