Tuesday, 5 May 2015

High salt diets maybe take some of it with a pinch

We have been talking about the environment and the risk of developing MS. ProfG has been talking about vitamin D and sunlight for the past few years and the MS Societies have responded to the interest, by spending millions on clinical trials in MS. 

More recently, we have had a post that has been our number one viewed post, which is about another risk factor. This is all about having a cat and it being protective for MS http://multiple-sclerosis-research.blogspot.com/2014/10/now-cats-are-risk-factor-for-ms.html

So next we should expect the supporting EAE study and put a cat near mice and they won't get EAE...I will bet.

If they did get EAE they would not be able to run away and would soon be cat food. 

However, would it be because the cat is protective or the more likely effect is that the mice would be bricking-it because the cat is a predator. This will stress the mice out and we know that stress is immunosuppressive..so they won't get EAE. 

As a rule you do not house predator and prey together for this reason.

Now another recent risk factor from last year was a high salt diet causing an increased risk of autoimmunity. 

So it was suggested that MacDonuts eaters and fast food munchers would have a risk factor for MS because of increased salt. (Would this fit with the demographics of MS and the increase risk in females...Is the rise of MS in countries like Iran linked to the arrival of fast food:-). Maybe a Scandinavian paper is on the way as they collect records on everything:-)

Anyway do an EAE experiment of high salt diet and mice and low and behold, animals got worse EAE so QED.

Let's do a trial to reduce salt and it should stop autoimmunity.

However, the animal data originally shown only increased salt and did not show that low salt was protective. In the experiments there was not much disease in the controls so in the words of Yaz "The only way is Up" So rather that do an experiment where disease in the controls is of usually susceptibility, there was no repeat and so we suspect clinical trial here we come. 

MD2 asked the question (Incidentally twice on the Nature site and they were removed both times and then blocked further comments) what is the relevance of the animal data because if you look at the equivalent dose used in the mice to translate from animals to humans, they need to eat/drink 600g salt a day. Compare this to the average human daily consumption of about 8g a day and 30g as an extreme.  So eating half a kilo of salt and you may well be dead?

So rather than being a killjoy/cynic and suggest it may have no translational value, one could ask a few questions before embarking on a clinical trial, costing millions and years.

Should we: (a) repeat the data, preferably independently (b) do a dose-response to show if the augmenting influence is dose-dependent;(c) Show there was control with a low salt diet; (d) Do it in other autoimmune diseases/strains to show reproducibility and importantly (e) Get disease established and see if a salt diet can influence disease in animals that is already sensitized, rather than see if you get autoimmunity on a high salt diet as indicated in the animal experiments.

A 4-6 week experiment in mice before a year or three clinical trial.

In animals (d) it is being done and the the idea is perhaps tanking, as some studies shown no influence of high salt diet on autoimmunity. So it is interest we see a bit of a repeat and it shows it is not clear cut. So maybe rather too early to be doing clinical trials.

Krementsov DN, Case LK, Hickey WF, Teuscher C. Exacerbation of autoimmune neuroinflammation by dietary sodium is genetically controlled and sex specific. FASEB J. 2015 Apr 27. pii: fj.15-272542. [Epub ahead of print]Multiple sclerosis (MS) is a debilitating autoimmune neuroinflammatory disease influenced by genetics and the environment. MS incidence in female subjects has approximately tripled in the last century, suggesting a sex-specific environmental influence. Recent animal and human studies have implicated dietary sodium as a risk factor in MS, whereby high sodium augmented the generation of T helper (Th) 17 cells and exacerbated experimental autoimmune encephalomyelitis (EAE), the principal model of MS. However, whether dietary sodium interacts with sex or genetics remains unknown. Here, we show that high dietary sodium exacerbates EAE in a strain- and sex-specific fashion. In C57BL6/J mice, exposure to a high-salt diet exacerbated disease in both sexes, while in SJL/JCrHsd mice, it did so only in females. In further support of a genetic component, we found that sodium failed to modify EAE course in C57BL6/J mice carrying a 129/Sv-derived interval on chromosome 17. Furthermore, we found that the high-sodium diet did not augment Th17 or Th1 responses, but it did result in increased blood-brain barrier permeability and brain pathology. Our results demonstrate that the effects of dietary sodium on autoimmune neuroinflammation are sex specific, genetically controlled, and CNS mediated

So good news there was again augmentation (after they toned down the induction protocol to get rubbishy weak disease) albeit marginal, in C57BL/6 strain mice and so repeats the Nature study....well sort of...... because they could not find any influence of Th17 cells, unlike the basis for the original study. 

I wonder what the human studies will find (NCT02261688) as it is already Tally Ho. Maybe the animal studies become irrelevant when the human studies say Tally Ho.

Bad news....still no report of dose response and then very bad news because the influence is not reproducible!

In an EAE susceptible strain the influence of salt diet is not reproducible and so sometimes no effect can be seen. Also no effect was seen in another C57BL/6 transgenic substrain.

Therefore between two individuals (strains) the results can be different. Furthermore the influence of salt was sex dependent in one strain but not the other.

The effect could be controlled by genetics meaning some individuals will show an effect and some won't, so the chances of a successful trial is diminished.

Because of the unmet need you may demand that the science community do human trials and in many cases we may be running before we can walk, and it is not the meeces fault when we trip up and fall.


  1. I think this salt stuff is only important if it leads to further understanding of the genetics and mechanisms of MS which then translate into treatments. Otherwise it is not worth millions of pounds of input: We know already that low to moderate salt intake is healthy for reasons unrelated to MS. I already avoid salty foods to avoid dehydration and irritating my bladder and in order to look after my cardiovascular system, but I still have PPMS. And I do not believe for one minute that salt intake played any significant role in my development of this disease.

  2. sounds like a reasonable point of view.

  3. What about the study being led by Dr. Farez in Argentina? ( RR of relapse multiplied by 3 for a high daily salt intake >3g/day)

  4. "incidentally twice on the Nature site and they were removed both times and then blocked further comments question"... :-O!!

    1. should we put up a post citing the paper but asking the question that altmetrics will link to? ;-).

    2. Good call! I've asked why my comments were deleted and now no comments are able to be made. Looks like a case of censorship to me! Maybe Nature are embarrassed that this paper slipped through the refereeing net, though the cynic in me suggests it was refereed by the authors' mates. I'll update if I get anything back.

  5. Huuumm think you can evaluate the salt intake with respect to course of MS, but related to a risk of developing MS think a little weak ... I for one have always had a "poor" salt diet, because practical sports since the mine 05 years of age. And the first symptoms of MS came after a strong throat infection ... It would be better to spend time and money on research outos strongest factors such as genetics, exposure to sunlight and possible contamination with the EBV virus and others. ..


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