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Three studies published today by collaborators at Yale, Harvard and MIT/Broad Institute suggest that dietary salt can speed the development of an MS-like disease in mice, and provide new insights on immune system activity involved in MS. While more research needs to be done to confirm a role for salt in triggering MS, or to determine whether reducing salt can inhibit MS immune attacks, these studies pinpoint new avenues for strategies that can decrease MS attacks. These studies were the product of a collaborative team effort funded in part by the National MS Society including a Collaborative MS Research Center Award to David Hafler, MD, at Yale University.

The three papers appear in the prestigious scientific journal Nature: 1) Drs. David Hafler, Markus Kleinewietfeld, (Yale University and Broad Institute of MIT and Harvard) and colleagues report on the ability of salt to drive aggressive immune cells called Th17 cells, in lab dishes and in MS-like disease in mice; 2) Drs. Vijay Kuchroo, Aviv Regev, Chuan Wu, (Harvard Medical School and Broad Institute of MIT and Harvard) and others report on the molecular events enabling salt to awaken and drive Th17 cells; and 3) Drs. Regev, Kuchroo and Nir Yosef (Broad Institute of MIT and Harvard) and others report on the network of regulatory factors that govern responses of the Th17 immune cells.

“This research sheds new light on factors that may be leading to the increase of MS, and points to potential solutions,” said Timothy Coetzee, PhD, Chief Research Officer at the National MS Society. “More research is needed in the emerging area of how diet may influence MS.”

Background: Over the last few decades, there has been an increase in the number of reported cases of MS and autoimmune diseases in some parts of the world. The cause of MS is not known, but a number of genetic and environmental factors are thought to influence whether a person will get MS. These newly published studies look at the possibility that dietary salt may play a role in inducing immune system activity in MS. The investigators conducted studies of immune cells in laboratory culture dishes and in mice with MS-like disease. To date, no studies have found a link between high salt intake and increased incidence of MS, but earlier findings from researchers at the University of Erlangen-Nuremberg suggested that excessive salt uptake can affect immune system activity. (Nature Medicine 2009 May;15(5):545-52)

The Studies: Dr. Hafler’s team administered salt in increasing amounts to human immune cells isolated in lab dishes. They found that higher than normal salt levels dramatically induced activity of immune cells known as T helper 17 cells or Th17 cells, which have been implicated in playing a major role in the immune attacks against the central nervous system in MS. The group also identified a number of cell signaling molecules that facilitate the influences of salt on immune cells. They then tested the effects of a high-salt diet in a mouse model called EAE, in which mice develop MS-like disease. Modest increases in salt levels sped up the onset of EAE and increased disease severity.

Dr. Kuchroo’s team explored the ways that salt might stimulate the activity of immune cells. They identified the protein “serum glucocorticoid kinase-1” (SGK1) as a critical signaling molecule that promotes Th17 cell activity. In this study, the team found that a modest increase in salt concentration induced both SGK1 and Th17 cell activity and that blocking SGK1 prevented the salt-induced increase in Th17 activity. In mice engineered to lack SGK1, the incidence and severity of EAE was reduced. Dr. Regev’s team reports on an elegant series of studies and computations revealing the network of other signaling molecules that govern responses of the Th17 immune cells.

Comment: Together, these studies provide new information on how activity of Th17 and other immune cells is regulated, offering the potential for new opportunities to develop therapies to control immune attacks in MS. Although these findings show important evidence that salt may be a factor in driving immune activity in laboratory settings, more research is needed to determine whether dietary salt plays a role in human MS. Carefully conducted studies of dietary habits would help to confirm the suggestion that dietary salt may be responsible for the increasing rates of MS and autoimmune diseases, and controlled clinical trials in which salt intake is limited in people with MS would be required to determine whether consuming less salt can reduce MS disease activity.

Read more about the combination of factors involved in MS development.

FREQUENTLY ASKED QUESTIONS

Do these studies prove that salt in the diet causes multiple sclerosis?
No. These studies use laboratory techniques to explore ways that immune cells implicated in MS immune attacks are altered upon exposure to higher than normal levels of salt.

Do these studies show that salt can make MS worse?
No. These studies provide an important new lead based on laboratory studies, but they do not provide evidence that dietary salt increases MS disease activity.

Is the incidence of MS increasing?
Yes. Over the last few decades, there has been an increase in the number of reported cases of MS in some parts of the world. There are probably many factors that are influencing this rise.

What would be the next steps to investigate this finding?
This new finding may lead to epidemiology studies that contrast the diets of people who eventually develop MS against the diets of those who do not. This would be an early step in helping to determine whether high dietary salt may contribute to susceptibility to MS.

Is there a clinical trial to determine whether a low salt diet can reduce MS immune attacks?
Not at this time, but these and further studies could lead to planning of such a trial.

Should I reduce my salt intake?
Research suggests that most Americans eat more salt than is recommended by federal guidelines, and even in the absence of direct evidence that MS immune activity is influenced by salt, reducing dietary salt is considered by most to be beneficial to the heart and circulatory system.

What is the National MS Society doing to investigate how diet impacts MS?
Currently the National MS Society is investing in research exploring several leads related to diet, including

• a clinical trial to determine whether dietary supplements of vitamin D can reduce MS disease activity;
• a clinical trial to determine whether a medical food can prevent cognitive impairment in MS;
• a clinical trial to determine whether an extract of green tea can help protect the brain and spinal cord from MS damage;
• previous trials testing the ability of omega-3 oil or ginkgo biloba to control MS and symptoms;
• studies of living microbes residing in the intestines, or “gut microbiome,” in MS, which could be influenced by diet;
• previous and ongoing studies exploring risk factors that influence whether a person develops MS, as well as factors that may impact a person’s disease course.