Patients with a genetically higher prediction of basal metabolic rate (BMR) may carry a greater risk of multiple sclerosis (MS); in fact, the rate may even anticipate the degree of severity, according to a study recently published in Metabolic Brain Disease.

The study included 115,803 individuals, almost 48,000 of whom had MS and the remainder were controls. Regarding the used data, there were nearly 10,000,000 single nucleotide polymorphisms from around 454,000 patients gathered from the UK Biobank.

To conduct the analysis, the authors did a 2-sample Mendelian randomization analysis. The genetic links came from the latest genome-wide association study (GWAS) summary statistics for MS as well as the most extensive GWAS database for BMR. Then, they analyzed which patients carried genetic variants conferring a more significant risk of MS.

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“Using summary-level data for MS and BMR levels from large European populations, our study demonstrated that a genetic increase in BMR by 1 standard deviation (a unit standard deviation=1358.32 kJ) was associated with a 28.3% increase in risk of MS,” the authors explained. “The high instrumental variable strength (F=79.76) provides strong evidence to support a causal role of BMR in MS susceptibility.”

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Moreover, apart from exploring the relationship between the risk of MS and genetic variants linked with higher BMR, Liu and colleagues assessed known MS risk factors. They found a connection between BMR and significant lifestyle determinants, such as obesity, smoking, and vitamin D deficiency, consequently proposing that BMR is a possible underlying pathophysiological pathway for all of them.

Although noteworthy, the detailed mechanisms by which BMR is related to MS need validation from further thorough scientific experiments.

“In this [Mendelian randomization] study, we provide novel evidence that a high BMR is an independent causal risk factor in the demyelination of [the central nervous system],” the authors wrote. “We believe that when the BMR increases beyond the compensable range, it might induce abnormal axonal electrical activity and thereby damage the myelin sheath.”

This novel study that identifies BMR as a possible pathophysiological pathway for MS could also play a role in population health. People who can change their food intake or activity patterns could palliate their risks due to an increase in BMR. Further investigations on BMR will allow a greater appreciation of the genetic epidemiology of MS, the authors conclude.


Liu C, Lu Y, Chen J, Qiu W, Zhan Y, Liu Z. Basal metabolic rate and risk of multiple sclerosis: a Mendelian randomization study. Metab Brain Dis. Published online May 11, 2022. doi:10.1007/s11011-022-00973-y