News that high-salt diets have been linked to autoimmune conditions has hit the headlines today, with BBC News reporting that "The amount of salt in our diet could be…leading to diseases such as multiple sclerosis."
However, the BBC's story is not based on trials of how much salt people eat and whether they go on to develop multiple sclerosis (MS), as you might expect. The story is actually based on studies looking at the impact salt has on immune cells, and how it affects the development of a condition similar to MS in mice.
MS is an autoimmune disease. These are diseases that occur when the immune system malfunctions, creating antibodies that attack the body's own cells. In MS, the immune system attacks the cells that make up nerve fibres.
This study found that mice fed a high-salt diet produced more immune cells called T-helper 17 (TH17) cells, which are involved in some autoimmune diseases.
These results are food for thought about the role high-salt diets play in the development of autoimmune diseases. But because the study was carried out in animals, it is unclear if similar results would be found in people.
We can't conclude that a high-salt diet causes MS from the results of this study. However, we do know that a high-salt diet is unhealthy and too much salt can cause high blood pressure.
Where did the story come from?
The study was carried out by researchers from Harvard Medical School, the Massachusetts Institute of Technology and the University of Salzburg, and was funded by the US National Institutes of Health and other research foundations in the US and Austria.
It was published in the peer-reviewed journal Nature.
The BBC report on the research was measured and accurate, emphasising that the findings were from early laboratory studies.
What kind of research was this?
This was a series of laboratory and animal studies investigating possible environmental triggers for autoimmune activity.
Experts suggest that genetics and gender play a key role in autoimmune diseases, but that environmental triggers are also a factor in the development of these disorders. The current research looked at the impact of salt on the production (or overproduction) of a specific type of immune cell, T-helper 17 (TH17) cells, which promote inflammation as part of an immune response.
One experiment moved beyond cells in a laboratory and looked at the effect of a high-salt diet on the development of a condition similar to MS, called experimental autoimmune encephalomyelitis (EAE), in mice.
As laboratory and animal studies, this series of experiments can provide clues about how salt may impact immune cell responses. However, they cannot tell us whether it directly affects the development of autoimmune diseases in people.
What did the research involve?
Several teams of researchers first looked into the molecular mechanisms that produce TH17 cells. This series of experiments suggested that a gene responsible for regulating salt levels in cells is involved in the TH17 cells signalling network (the series of molecular activity that enables communication between cells).
They found that when cells were exposed to increased concentrations of salt, this gene (SGK1) was activated and increased the development of TH17 cells. This finding led to the researchers conducting experiments using mice with EAE.
The researchers took three groups of mice:
- group 1 lacked the SGK1 gene and was fed a normal diet
- group 2 lacked the SGK1 gene and was fed a high-salt diet for three weeks
- group 3 had the SGK1 gene and was fed the same high-salt diet as group 2
The researchers then determined whether the mice developed EAE so they could look at the role played in the disease by the SGK1 gene and salt exposure.
What were the basic results?
The researchers found differences between the groups in the number of TH17 cells produced, as well as the likelihood of the mice developing EAE, and the severity of the condition:
- group 1 (which lacked the SGK1 gene and was fed a normal diet) had fewer TH17 cells and less severe EAE
- group 2 (which lacked the SGK1 gene and was fed a high-salt diet) appeared to be protected against the development of EAE
- group 3 (which had the SGK1 gene and was fed a high-salt diet) had more frequent and severe EAE than mice fed a normal diet, and more TH17 cells than group 2
How did the researchers interpret the results?
The researchers say that this data suggests that high salt intake allows for an increase in TH17 cells in a way that relies on the SGK1 gene activating. They feel this "therefore has the potential to increase the risk of promoting autoimmunity."
This early stage research suggests that increased salt consumption may play a role in the production of a certain type of immune cell (TH17). The study further suggests that a high-salt diet can increase the rate and severity of an MS-like condition in mice (EAE).
These experiments are an interesting insight into the possible interplay between the genetic and environmental factors involved in autoimmune diseases. However, at this stage what this means for human autoimmune disease is not clear.
This research should certainly not be interpreted as meaning that a high-salt diet causes multiple sclerosis in people (although it can cause high blood pressure).
While the term 'autoimmune diseases' may seem to imply a similar set of conditions, there are in fact a variety of different autoimmune conditions. The different factors involved in these conditions is unlikely to be the same across all conditions.
The researchers say that while their results indicate that the gene SGK1 plays a key role in autoimmune responses, "it is likely that other immune cells and pathways are also influenced by increased salt intake," and that their results "do not exclude additional alternative mechanisms by which an increase in NaCl [salt] affects TH17 cells."
This means that these experiments outlined a possible way that a single environmental trigger (salt) could interact with a single gene (SGK1), and how this could influence the production of a type of immune cell (TH17 cells) that has been implicated in autoimmune disorders.
Other complex processes are likely to be involved, because many other cells also produce proteins that are involved in autoimmune disorders.
As the researchers themselves say, their results raise "the important issue of whether increased salt in westernised diets and in processed foods contributes to an increased generation of pathogenic [disease causing] TH17 cells and for an unprecedented increase in autoimmune disorders."
A great deal more research is needed to find out whether, and how, salt consumption impacts on both the development and severity of autoimmune diseases in people. Such research could involve cohort or case control studies to establish whether or not there is a link between dietary salt intake and multiple sclerosis, or other autoimmune diseases.
Randomised controlled trials would be needed to firmly establish the role that salt plays in autoimmune conditions. Commentators point out that "the risks of limiting dietary salt intake are not great, so it is likely that several such trials will be starting soon."
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 7 March 2013
Mail Online, 6 March 2013
Links to the science
Nature. Published online March 6 2013