People with multiple sclerosis (MS) who have higher sodium intake show an approximately 3 times higher risk for exacerbations in symptoms as well as disease activity, compared with those with lower sodium intake, a new study shows.
The Argentinean authors were cautious about drawing conclusions, however, noting that, with various limitations, the study falls short of proving a causal relationship.
"This small observational study suggests that there may be a positive correlation between sodium intake and MS disease activity," lead author Mauricio Farez, MD, from the Raúl Carrea Institute for Neurological Research, Buenos Aires, Argentina, told Medscape Medical News.
"However, we are just starting to address the effect of sodium intake in MS patients, and further and larger studies are required to establish whether sodium restriction is a potential add-on therapy to MS patients."
The study was published August 28 in the Journal of Neurology, Neurosurgery & Psychiatry.
The study involved 2 separate groups of patients with MS. One group included 70 patients with frequently relapsing MS who were followed longitudinally for 2 years. The patients' sodium intake was estimated from urine and serum samples taken on 3 separate occasions over 9 months, and regression analysis was used to determine the effect of the intake on their disease activity.
Those findings were then replicated in a separate group of 52 patients with MS.
The patients had an average daily salt intake of approximately 4 g per day, with men showing higher daily intake than women.
After a multivariate adjustment for factors including age, sex, disease duration, treatment, vitamin D levels, body mass index, and smoking status, higher sodium intake was significantly associated with greater exacerbations. Compared with patients with a sodium intake below the World Health Organization recommendation of 2 g per day, those with an average daily intake of 2 to 4.8 g had a symptom exacerbation rate that was 2.75 times higher (95% confidence interval [CI], 1.3 - 5.8), and among those with an average daily intake of 4.8 g or higher, the risk was 3.95 times higher (95% CI, 1.4 - 11.2; P < 0.001 for trend).
Sodium intake levels further correlated with MS activity on MRI. Patients with sodium intake above the national average showed a 3.4-fold increased chance of developing a new lesion on MRI and were found to have, on average, as many as 8 more T2 lesions.
"Knowing that there are many potential pathways to explain this association, we hypothesized that we were going to find a positive correlation [between sodium and MS], but we did not expect to find this magnitude of an effect," Dr. Farez said.
Among the theories on the mechanisms that could explain the association is the possibility that sodium intake boosts the generation of TH17 cells, which are the subset of T cells that are primarily implicated in the autoimmune response in patients with MS, Dr. Farez said.
He noted that another potential, yet less clear mechanism is the modification of the renin-angiotensin system (RAS), which has been shown in animal models to exacerbate MS and activate TH17 cells.
"High sodium intake usually suppresses the activation of RAS, but salt-unresponsive RAS activation can be seen in hypertensive or diabetic patients, so the role in MS is yet to be determined," Dr. Farez explained.
Still another theory is that the modulation of gut flora caused by high sodium intake could have an effect because gut flora interacts with the immune system and could therefore affect MS disease activity.
On the other hand, among the study's limitations is that plenty of factors contribute to a reverse causation, Dr. Farez underscored.
"Individuals with more relapses, for instance, may have received more steroids and therefore had increased salt intake and excretion due to the higher disease activity and not the other way around," he said, "although we think this is unlikely because we separated sodium intake assessment from steroids intake."
In addition, patients with increased disease activity who may have hypothalamic lesions can develop inappropriate antidiuretic hormone secretion and therefore excrete higher amounts of sodium.
The authors noted that they ruled out the possibility, however, by measuring serum concentration in the serum and excluding patients with hyponatremia.
MS expert Gaurav Guliani, MD, an assistant professor of neurology at the University of Minnesota Medical School, in Minneapolis, agreed that the study, although intriguing, has some caveats.
"[They are] quite interesting findings and it's a well designed study, but I would be wary of drawing general clinical implications given that this is an observational study of a small cohort," he told Medscape Medical News.
"It is indeed surprising to see that patients with a high sodium intake had over 3 times the chance of developing a new lesion on MRI, as well as about 3 times the chance of an exacerbation; whether this is due to sodium intake, or merely correlated to the sodium intake, is the next question that needs to be answered," he said.
He also agreed that as the research advances, an important focus should be on the effects of salt reduction in patients with MS, he added.
"There is no evidence yet that MS patients who reduce salt intake show improvements in symptoms. This is the next step — to see if reducing salt intake actually makes a difference."
The study received support from the Raúl Carrea Institute for Neurological Research FLENI and a grant from Novartis Argentina, and Merck-Serono Argentina. Dr. Farez received honoraria and professional travel stipends from Merck-Serono Argentina and Novartis Argentina. Coauthor Jorge Correale is a board member of Merck-Serono Argentina, Novartis Argentina, Biogen-Idec LATAM, and Merck-Serono LATAM, and he received reimbursement to develop educational presentations for Merck-Serono Argentina, Merck-Serono LATAM, Biogen-Idec Argentina, Novartis Argentina, Novartis LATAM, Genzyme Argentina and TEVA-Tuteur Argentina as well as professional travel/accommodation stipends. Dr. Guliani has disclosed no relevant financial relationships.
J Neurol Neurosurg Psychiatry. Published online August 28, 2014. Abstract
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Cite this: High Sodium Intake Linked to Increased MS Exacerbations - Medscape - Sep 03, 2014.