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Study Questions Influence of High-Salt Diet on MS

SUMMARY

  • Some recent studies have suggested that high intake of salt in the diet might influence MS disease activity and progression, but other studies have not confirmed that link.
  • In work partly funded by the National MS Society, researchers took advantage of data accumulated from a previous clinical trial involving 465 people with possible early signs of MS (CIS) whose salt levels in urine were measured over the course of 5 years.
  • They found no connection between salt intake and MS activity.
  • The study, “Sodium Intake and Multiple Sclerosis Activity and Progression in BENEFIT,” was published in the July 2017 issue of the Annals of Neurology (2017;82:20-29).
  • Although this study does not support a link between high-salt diets and MS disease activity, research suggests that most Americans eat more salt than is recommended by federal guidelines. Reducing dietary salt is considered by most to be beneficial to the heart and circulatory system.

DETAILS
Background: Several recent studies have suggested that dietary salt (sodium chloride) could potentially influence MS disease activity and progression. For example, one study of 70 people with relapsing-remitting MS, who were followed for two years, found that higher levels of salt measured in urine samples were associated with a higher rate of relapses and larger brain MRI lesions. In addition, mice fed a high-salt diet developed a more aggressive course of EAE, a laboratory model of MS. But two studies in pediatric MS did not find a relationship between self-reported salt intake and MS risk or relapse rates. Resolving this question is important because it offers the possibility that reducing salt intake might improve a person’s overall health and their course of MS.

This Study: In work partly funded by the National MS Society, researchers set out to determine if a high-salt diet is associated with faster conversion from a first neurologic episode (known as clinically isolated syndrome or CIS) to a diagnosis of definite multiple sclerosis, or with MS disease activity. Kathryn C. Fitzgerald, ScD (Johns Hopkins School of Medicine), Alberto Ascherio, MD, DrPH (Harvard T. H. Chan School of Public Health) and colleagues took advantage of data accumulated from a previous clinical trial involving 465 participants who participated in a trial called BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) over 5 years. The trial compared benefits of giving interferon to individuals with CIS early versus later. Each person provided an average of 14 urine samples throughout the five-year follow-up. The researchers estimated average long-term sodium intake from the multiple urine samples, adjusting for age, sex, height, weight, where participants lived, and many other variables.

Results: Researchers found that neither average nor high urine sodium levels were associated with conversion to definite MS. They also weren’t associated with new MRI lesions at any point in the five years, relapse rates, or progression of disability. These results suggest that high sodium intake does not play a major role in influencing MS disease course or activity in people treated with interferon, at least in the early stages of the disease.

While the study has several strengths, including its length, large sample size, and systematic collection of data, it has limitations: BENEFIT participants were treated nearly uniformly with interferon, and the results may not apply to people on other therapies or no therapy. In addition, participants in the BENEFIT trial were primarily Caucasian and resided in Europe and Canada, and it isn’t known if similar results would apply to other populations and ethnicities. The results also don’t answer the question of whether salt intake affects the risk of developing MS in the first place.

The study, “Sodium Intake and Multiple Sclerosis Activity and Progression in BENEFIT,” was published in the July 2017 issue of the Annals of Neurology (2017;82:20-29).

Comment: Although this study does not support a link between high-salt intake and MS disease activity, research suggests that most Americans eat more salt than is recommended by federal guidelines. 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.

Read More: Diet, along with exercise, cognitive health, and other healthy behaviors can make a big difference to how you feel as you deal with MS. Learn more about living well with MS

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New Lab Studies Add Evidence That High Salt Diets Increase Inflammation and May Have Implications for MS

Summary
• The results from two recently published laboratory studies suggest that high levels of salt shift the balance of the immune system toward inflammation, and that salt alters the function of several types of immune cells pertinent to MS.
• These two studies, which were both published in the Journal of Clinical Investigation, were led by Dr. David Hafler (Yale University) and Dr. Dominik Müller (Max-Delbruck Center, Berlin, Germany).
• Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Background: Eating high levels of salt, which is part of the typical Western diet, has been linked to heart disease, chronic inflammation, and cancer. Recent lab reports have also suggested that dietary salt can speed the development of the immune attack in an MS-like disease in mice, and that the mouse disease responds differently to salt depending on the gender and genetic makeup of the mice. One small study in people found a possible link between dietary salt levels and relapses in people with MS, but this study suggested a link, which is not the same as establishing an actual cause. So far, laboratory findings related to the effects of salt have been stronger than the few studies that have been reported in people. Understanding whether high dietary salt is a risk factor for developing MS or for worsening disease activity is an active area of research.

The Studies: Two studies recently published in the Journal of Clinical Investigation suggest that high dietary salt affects two types of immune cells in a way that increases inflammation, a state that is generally considered harmful in MS. A study by National MS Society-supported researchers at Yale University and Harvard Medical School led by David Hafler, MD, investigated the effects of high salt on regulatory immune cells called “Tregs.” Tregs normally suppress immune responses by other immune cells, but in people with MS Tregs have been shown to be less able to perform this helpful function to turn off attacks. The team showed in mice and in cells in lab dishes that high salt blocks the ability of Tregs to suppress potentially harmful immune cells, and shifts Tregs toward activity that increases inflammation.

The other study, by an international team led by Dominik N. Müller at the Max-Delbruck Center in Berlin, Germany, investigated immune cells called “macrophages.” This study showed that high salt blocks the activation of a subset of macrophages, reducing their ability to suppress inflammatory cells and creating an imbalance in the immune system. In mouse models, high salt diets also delayed wound healing.

Comment: Taken together, these laboratory studies add new evidence that high levels of dietary salt may increase inflammation and autoimmunity, and decrease the ability of regulatory cells and processes to limit harmful immune cell activity. More studies are needed to determine the possible role of a high-salt diet in the risk of developing MS and whether reducing salt intake may be helpful for reducing disease activity in people with MS. Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Read more about dietary factors that may play a role in MS
Read more about research on the immune system in MS

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