Sodium intake and multiple sclerosis activity and progression in BENEFIT

Abstract

Objective: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability.

Methods: BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes.

Results: Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles.

Interpretation: Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.

Figure 1

Estimated 24-hour urinary sodium excretion using the Tanaka et. al equations by hour of sample collection (A) and by study visit (B). (C) Spaghetti plots of individual variability over follow-up in estimated 24-hour sodium excretion from selected study patients. Selected patients plotted are those having a patient-specific median excretion (across follow-up) at the 5th, 25th, 50th, 75th and 95th percentiles of the distribution of patient-specific overall median values.

Figure 2

Relation between estimated 24-hour urinary sodium excretion using the Tanaka equations and MS outcomes from months 6 through 60 for sodium intake dichotomized at the median (A, B) and quintile categories (C, D). (A) Median analyses: Conversion to CDMS (P=0.50), (B) Median analyses: conversion to MDMS (P=0.12), (C) Quintile analyses: Conversion to CDMS (P=0.88), (D) Quintile analyses: conversion to MDMS (P=0.10) , (E) relapse rate , (F) change in EDSS. Estimates are adjusted for age, sex, randomization status (IFNB-1b, placebo), CIS onset type (multifocal, monofocal), 25-hydroxyvitamin D status, and body mass index.

Figure 3

Relation between estimated 24-hour urinary sodium excretion using the Tanaka equations and MRI outcomes from months 6 through 60. (A) relative rate of CNAL, (B) change in T2 lesion volume, (C) change in brain volume. Estimates are adjusted for age, sex, randomization status (IFNB-1b, placebo), CIS onset type (multifocal, monofocal), 25-hydroxyvitamin D status, and body mass index.