Thursday, 1 June 2017

Salt and Autoimmunity...

One un-reproducible Nature/science/Cell paper sparks a clamour to research a topic and spawns a load of others. Only the other day we were presenting data about some other group not being able to reproduce the New England Journal of Medicine finding that 50% of people with MS had antibodies against the Kir 4.1 potassium channel.

So on we go with the Salt story. It was suggested that dietary salt is the cause of autoimmunity a few years ago. At the time MD2 did question the animal data on which part of the story was based as the amount of salt was so high, humans would be vomiting their autoimmunity on. It made you wonder. 

Although the original observations were kind of reproduced, it was all rather unconvincing. 

I am happy to believe that salt intake is a risk factor for many things, but is it the major player?

In the paper below they assessed salt content by the sodium in urine in a group of people with their first reported episode of demyelination and the team then looked to see whether those with higher salt levels went on to develop Multiple Sclerosis or not.

Can you guess the answer?

Fitzgerald KC, Munger KL, Hartung HP, Freedman MS, Montalb├ín X, Edan G, Wicklein EM, Radue EW, Kappos L, Pohl C, Ascherio A. Sodium intake and multiple sclerosis activity and progression in BENEFIT. Ann Neurol. 2017 doi: 10.1002/ana.24965. [Epub ahead of print].


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.


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 (IQR: 13 to 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, EDSS) and magnetic resonance imaging (MRI) outcomes.


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% 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 -0.25-0.04; change in EDSS: -0.01; 95% CI: -0.09-0.08; relapse rate HR: 0.78; 95% CI: 0.56-1.07). Results were similar in categorical analyses using quintiles.


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.

Yep... take this with a pinch. 

However I wonder if salt was the risk factor for autoimmunity, whether this is the right experiment. 

Does urinary salt actually reflect, dietary salt?

If it is about risk then surely the salt level needs to be measured before the developent of the problem, which is before the clinically isolated syndrome. 

Likewise, a case has been made that vitamin D levels are a risk factor for MS. How many trials have been done after MS has started (loads of unconvincing studies) and how many prevention trials have been done (I think None...ProfG can correct me if I am wrong). 
Are we asking the right question in the trials we are doing?

For vitamin D, it is more sensible to study other conditions like type I diabetes, so you don't have to wait 35years for disease to occur and show itself. But if every clinician in every disease is jumping on the vitamin D trials bandwagon, doing the same type of trials is a lot of trials....a quick search on clinical shows over 3,000.

Maybe simply ensuring  one/two descent and definative experiments in Scotland or Scandarnavia to ensure that all pregnant mums are vitamin D repleat and that their children are vitamin D repleat from birth to adult hood and see if this makes a difference.


  1. Why not treat vitamin d deficiency in everyone and then it can be ignored as a risk factor. We know that levels in many are too low even for bone health. You do not fix chronic malnutrition with a good meal later in life and vitamin d is about chronic malnutrition not a magic drug.

  2. I was diagnosed as vit D deficient and given 600mg daily supplements. After 6 months I went back to the Dr and asked if they were going to retest blood sample to ensure that my vit D levels were now within normal range. I was told "no" the supplements will be enough.
    Two things here - I dont know any other doctors / surgeons who practice medicine without a feedback loop....... "so surgeon, how many brain operations have you done....50 .... and of those 50, how many survived....... I dont know...."

    and secondly, the figures that they are aiming for are from the 1950's and current research shows that the "normal range" should actually be much higher -
    than is what is currently aimed for - into the 1000's not 100's


Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.