University of Vermont

Krementsov and Teuscher Study Finds High Salt Intake Could Be Risk Factor for M.S.

Dimitry Krementsov, Ph.D.
Dimitry Krementsov, Ph.D., UVM Research Associate in Medicine. (Photo: COM Design & Photography)

New research published by University of Vermont (UVM) researchers in the August 2015 issue of The FASEB Journal suggests that the effects of salt on multiple sclerosis (M.S.) could be governed by an individual’s genetics and/or sex/gender.

The study, authored by Dimitry Krementsov, Ph.D., research associate in medicine, and Cory Teuscher, Ph.D., professor of medicine, and colleagues, showed that in mice, diets high in sodium may be a novel risk factor in the development of M.S. by influencing immune cells that cause the disease. Although this research does implicate salt intake as a risk factor, it is important to note that dietary salt is likely just one of the many environmental factors contributing to this complex disease, and very much influenced by one’s genetic background.

“We hope to provide a comprehensive understanding of how and why environmental factors interact with individuals’ unique genetic make up to influence autoimmune diseases such as M.S.,” says Krementsov.

There is strong evidence supporting the role of environmental factors interacting with genes in M.S., adds Krementsov, “but we understand very little about how that happens.” His team’s latest research findings suggest a sex-specific genetic control of the response to salt, which is consistent with the statistics on who develops M.S.: the disease is three to four times more common in women than men.

Several previously published papers suggest that higher salt intake causes more progression of the disease in some individuals.

To gain a clearer understanding of this relationship, Krementsov and colleagues fed a high salt diet or a control diet to three genetically different groups of mice. Researchers then induced a disease in these mice that mimics human M.S. In one genetic group, both males and females fed a high salt diet showed worse clinical signs of the disease. In the other genetic group, only females showed a negative response to salt. In the third genetic group, there was no response to salt. Genetics were the critical factor. In the mice that did respond to salt, there were no direct changes in the function of their immune cells, but they showed signs of a weakened blood-brain barrier. Immune cells must pass through the blood-brain barrier in order to enter the central nervous system; the more immune cells that pass this barrier, the greater the breakdown. Krementsov and his colleagues saw a correlation between the salt intake and this breakdown.

“Specialized organs in the brain called CVOs [circumventricular organs] can sense what’s going on in the blood, including electrolytes,” explains Krementsov. “Salt may influence the brain directly and control how tight the blood brain barrier is.”

“As is the case with other things, you need to get enough salt so your body functions properly, but not too much or things start to go haywire,” says Gerald Weissmann, M.D., editor-in-chief of The FASEB Journal. “This report helps shed light on what can go wrong in individuals with genes that make one susceptible to autoimmune disease. It also helps us understand how much salt is just right for any given individual.”

The research team, who in addition to Krementsov and Teuscher, includes Laure Case, Ph.D., former UVM postdoctoral associate, and William Hickey, M.D., professor of neurology and pathology and acting chair of pharmacology and toxicology at Geisel School of Medicine at Dartmouth, were able to identify some candidate genes that might be responsible for this phenomenon, but more research is needed to determine which genes play a specific role and whether or not this also occurs in humans.

Next up for Krementsov and Teuscher is an M.S. Society-funded project looking at gene-by-environment interactions in vitamin D. According to Krementsov, vitamin D deficiency is a well-established risk factor in the development of M.S.

(This article was adapted from a news release produced by Cody Mooneyhan of FASEB.)