Medical Research: What is the background for this study? What are the main findings?
Dr. Krementsov: Multiple sclerosis (MS) is the most common disabling neurologic disorder affecting young adults. The disease is initiated by the individual’s own immune system attacking the central nervous system (brain and spinal cord).Multiple sclerosis is complex and is controlled by the interplay between sex/gender, genetics, and environmental factors. How this happens is not well understood, but an intriguing clue is that MS incidence over the last 50-100 years has been increasing in women and not men, suggesting that a recent environmental change is affecting MS preferentially in females.
There are several well-documented risk factors for Multiple Scleroisis, including Epstein-Barr virus infection, low sunlight exposure, low vitamin D, and smoking. Recent studies have suggested the existence of a new risk factor – high intake of dietary salt. In our study, we sought to understand how this environmental factor may interact with genetics and sex.
We used an animal model of MS, called experimental autoimmune encephalomyelitis (EAE), in laboratory mice. The advantage of this approach is the ability to precisely control both the genetics and the environment, something that cannot be done in epidemiological studies in humans. Just as in previous studies, we found that when mice were fed a high salt diet, their MS-like disease got worse.
Importantly, we found that this was dependent on genetics and sex; when we varied the genetic background of the mice, we saw three different outcomes:
1) an effect of salt in both males and females,
2) an effect only in females, and
3) no effect in either sex.
Medical Research: What should clinicians and patients take away from your report?
Dr. Krementsov: First of all, as with all studies in animal models, caution should be exercised not to over-interpret the data. After all, mice are not humans, and a large increase in dietary intake of salt in our study over a short period of time may be tricky to extrapolate to a lifetime of high salt consumption by a human. Nonetheless, while findings support the idea that dietary salt may indeed be a risk factor in MS pathogenesis, they also show that this can be strongly influenced by genetics and sex (i.e. it would affect only some individuals). It is also intriguing that we saw female-specific effects. Since Multiple sclerosis incidence is rising only in females, one would speculate that increased salt intake due to increased prevalence of processed foods in the 20thcentury may be a contributing factor.
It is clearly premature to make strong recommendations about dietary salt intakes for Multiple Sclerosis patients (or those at risk for developing MS). However, given that high salt intake is associated with other adverse outcomes such as cardiovascular disease, it may be wise to consider the already established dietary guidelines.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Krementsov: It would be interesting to identify if the salt effects in MS and its models are dependent on specific genes. Our study identified a few candidates for such genes, but at this point these are highly speculative.
Another unanswered question is exactly how does dietary salt promote disease in Multiple Sclerosis or its models? Initial studies suggested that sodium may be stimulating the activation of immune cells, called T helper cells, which can initiate and promote MS. In our study, we found no evidence of this, but we instead found that high dietary sodium may be promoting the disruption of the blood-brain barrier, a thin “wall” of cells that prevents the passage of potentially dangerous immune cells from the blood into the brain. Further studies will be needed to sort out how this may happen, and which mechanism may be more important.
Perhaps most importantly, epidemiologic studies measuring salt intake in Multiple Sclerosis patients and comparing this to disease incidence or progression will be needed. One such study has already been published, but larger and more systematic studies are needed, possibly stratifying on ethnic background to control for genetics.
FASEB J. 2015 Aug;29(8):3446-57. doi: 10.1096/fj.15-272542. Epub 2015 Apr 27.
Exacerbation of autoimmune neuroinflammation by dietary sodium is genetically controlled and sex specific.
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Dimitry N. Krementsov PhD (2015). Could Increased Salt In Processed Food Contribute To Rise in MS Cases? MedicalResearch.com