Can we really blame salt for the rise of immune diseases?
Perhaps. And it is only just getting recognized.
Written by Elisabeth Huber, Srivaishnavi Loganathan and Barbara Safaric. Edited by Kristina Popova.
For details of individual contributions see below.
To Amanda, it just felt like there was something in her eye. The strange sensation, which she noticed during her regular workouts in the gym, appeared soon after she stopped nursing her 10-months-old daughter. It must be the stress, she assumed, and didn’t give it much thought. “And then it went away,” she remembers, “so I didn‘t worry about it until about eight months later it came back.” This time, the symptoms refused to leave and Amanda Windhof, Ph.D., who is now a lifestyle advocate for multiple sclerosis (MS), began her uneasy journey towards the diagnosis.
She paid a visit to an ophthalmologist, who couldn’t determine anything wrong with her eye. Next, there was a check-up with a neuropathologist, who suspected that something could be putting pressure on her optic nerve. She was prescribed eye drops and sent home. However, nothing had changed. After a while, she was scheduled for an MRI scan. “I was sitting in the neuro-ophthalmologist’s waiting room, and there were all these magazines about living with multiple sclerosis,” continued Amanda. “And I really didn’t make the connection”.
With the MRI results, Amanda was further referred to a neurologist who made the final diagnosis: multiple sclerosis. Her MRI scans showed lesions in the brain as well as in the spinal cord, the telltale signs of MS.
Amanda’s experience is not uncommon. On average, the path to the MS diagnosis involves five appointments with a medical specialist over 6 months. Only in Europe, around 700,000 people are suffering from MS, which is a narrow glimpse into the scope of autoimmune diseases. This umbrella term includes a staggering number of 80 to 100 different diseases, where the body’s immune system turns onto itself and attacks its own healthy cells. Autoimmune diseases affect 5 to 10% of the global population — amounting to the number of cancer and heart disease patients combined, and the numbers keep rising.
There is no specific cause for developing an autoimmune disease, and it is commonly accepted that autoimmune diseases can be triggered by a combination of genetic and environmental factors, such as infections, ecology and nutrition.
There is currently no cure for autoimmune diseases. The available treatments can only relieve the symptoms and improve the quality of life. In fact, patients have to be in therapy throughout their lifetime. Science has answers to how the immune system can be modified to improve their lives but still no answers to curing them.
Certainly, the sudden expansion of immune system related diseases cannot be explained by the genetic factors alone. “Genetic predisposition for developing an autoimmune disease on its own is not sufficient, you need a trigger,” explains Dr. Guru Krishnamoorthy, an immunologist at the Max Planck Institute for Biochemistry in Munich, Germany. Thus, researchers have shifted their focus to investigating changes in our behaviors — the so-called environmental factors, including our diet.
The major change in our diet over the last decades is the increased consumption of salt in the form of processed and junk foods. It might come as a surprise “that something as simple as table salt could have the potential to modulate our immune system,” says Prof. Christina Zielinski, head of cellular immunoregulation lab, Technical University Munich.
Our immune system is the first line of defense against worms, viruses, parasites and bacterial infections. And T cells, the front line soldiers of the immunity army, direct and orchestrate the responses of the immune system against these infections. T cells are very broadly categorized into helper T cells and cytotoxic T cells. And like all cell types, helper T cells and cytotoxic T cells also have subtypes. Here we mention only some subtypes of the helper T cells. The subtypes of helper T cells are: Th1, Th2, Th9, Th17, Th22, follicular T cells, regulatory T cells and Th-GM-CSF cells, depending on the cytokines (hormonal messengers) they produce. Complicated? Maybe the figure below would help you with it.
Th1 cells produce cytokines like interferon (IFN)-gamma and interleukin (IL)-2 and generate responses against bacteria and viruses. They also participate in the development of autoimmune diseases. On the other hand, Th2 cells produce cytokines like IL-4 and IL-13. Th2 cells are mainly known to generate responses against helminths or worms. Some studies also report Th2 cells’ involvement in allergic diseases. Th17 cells produce cytokine IL-17 and have been linked to autoimmune diseases like rheumatoid arthritis and lupus.
How a naive precursor T cell decides which path to take is still unclear to scientists. But the bigger question is: how does salt fit into the whole picture? In fact, salt was never considered as a modulator of our immune system because of its consistent concentrations inside our body (mostly measured in blood). Most scientists thought of it as a research path with a dead end. “You cannot even make a patent out of sodium chloride anymore,” joked Prof. Zielinski while talking about her grant application experience. But a few scientists like Prof. Zielinski and her team did tread the road not taken.
Initial studies that brought table salt to limelight came from groups at Yale, MIT and Harvard. Scientists found that “modest increase in salt concentrations” induced Th17 cell responses via a protein called Serum Glucocorticoid Kinase 1 (SGK1). SGK1 belongs to a class of transcription factors (protein molecules that are involved in the process of copying DNA into RNA molecules) and is responsible for maintaining the balance of salt concentrations in different cells. Adding salt to mouse cells not only increased SGK1 protein concentrations in cells but also triggered Th17 cell production. Supporting the in vitro (cells cultured in a dish) studies, animal studies where high salt diet was fed to mice with experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) increased Th17 cell production in the animals and accelerated the disease progression.
On a similar quest to understand how to deal with immune diseases, Prof. Zielinski and her lab decided to find out how the cells of the immune system interact with their microenvironment. Prof. Zielinski’s lab focused specifically on allergies of the skin (atopic dermatitis). They found that salt concentrations varied between the skin area affected by allergy and the healthy surrounding skin. They also found that salt was a factor able to induce a naive T cell to become Th2 cells. And SGK1 plays a role in this transition.
“We more or less accidentally found out that sodium really has profound effects on T cell functions,” said Prof. Zielinski. According to her, the next question is to understand “how the T cells really sniff out the salt.” Whether the T cells have “antennas” that pick up high salt signals is not known. But some transcription factors in the cells, like the SGK1, are sensitive to osmotic stress. It is possible that high salt concentrations cause osmotic stress in cells, which is then picked up by the transcription factors, thus deciding the fate of a T cell. But at this point, it is only a hypothesis.
“We are more complex than just our own cells,” says Prof. Zielinski. Our cells, for example, also contain genetic material from bacteria and viruses. We even house microbes in our gut — the gut microbiota. Evolutionarily, our immune system was designed to ward off this evil. And yet, we shelter microbes in our body and they become part of our defense system when necessary.
Like our immune cells, gut microbiota is also sensitive to changes in our diet. And the fact that gut microbiome can also play a role in diseases is only beginning to be acknowledged by the scientific community. Dr. Krishnamoorthy and his team are studying the relationship between microbiota and the immune system response. Specifically, they are trying to identify metabolites produced by microbiota and their effects on the development of autoimmune diseases.
„We believe that microbiome is the key factor to tip the balance towards the immune disease,” says Dr. Krishnamoorthy. Our microbiome, made up of trillions and trillions of microbes, is always changing and adapting to new circumstances.
However, he cautions: “There is not going to be one solution — one metabolite, one bacteria, one pathway or one cell type. All autoimmune diseases are multi-component diseases and there are many ways they can be affected.”
Another collaborative study from different institutions in Germany showed that high salt concentrations affected the gut microbiome in mice. Specifically, Lactobacillus murinus — a strain of beneficial bacteria also present in the human gut — was depleted in mice consuming high amounts of salt. When autoimmune encephalomyelitis was induced in mice, the high salt diet aggravated the disease and the level of the unfavourable Th17 cells elevated. After treatment of the sick mice with L. murinus, the level of Th17 cells decreased and this provides the first idea for a treatment of autoimmune diseases caused by an unhealthy diet. The group also did a pilot study in humans. The healthy participants were given tablets with high concentrations of salt and this reduced the survival of Lactobacillus species in their intestine and induced Th17 cells.
All these reports and studies are pointing towards the same conclusion: salt is one of the triggers for diseases of the immune system. But what can we do about it?
Despite an ample amount of research on the connection between the overall well-being and leading a healthy lifestyle, doctors rarely take a holistic approach. In Amanda’s experience, medical professionals “concentrate on the medications, but never really ask how much I exercise or how my diet looks like”.
“There is so much pushback, it’s frustrating,” she said. “My first doctor basically dismissed [my nutrition plan] and was recommending donut stores I should go to.”
However, the tide is slowly changing as there is a growing body of evidence on how environmental factors are influencing our health.
For Dr. med. Claudia Löffler, who is an oncologist and nutritional expert working at the hospital of the Julius-Maximilians University Würzburg, “nutrition is such an important issue that still doesn’t get enough attention”. She is convinced that the diet is an important field in the health care sector, and especially in the field of oncology (we will follow up on that in our next article).
Thus, for Dr. Löffler not only the academic medicine, but also the overall well-being of a patient is very important. This can be achieved by additional naturopathy, stress reduction, relaxation and following a balanced diet. She recommends to her patients to eat “colorful” foods, including many vegetables, fruits, whole grain products and especially avoiding processed, canned food. Dr. Krishnamoorthy agrees: “For sure, at least on the microbiome level, diet can have a huge impact”.
But how much salt is actually healthy and recommended? And what amount of salt is harmful to the human body?
The German Society for Nutrition recommends not more than 6 grams of salt per day (g/d), which is roughly the amount of salt that fits onto a teaspoon. In a low salt and strict diet, 1.2–3 and 0.4–1 g/d of salt are allowed, respectively. Generally, for someone following a normal balanced diet, which includes sausages, cheese and bread, there is no danger of consuming too less salt. On the contrary, people in Germany eat on average way more salt than is recommended — more than 15 g/d (10 g/d for males and 8.4 g/d for females). So far, we found no studies which would show that consuming such high amounts of salt has any advantages for the human body.
Since salt is an inorganic fusion of sodium and chloride ions, it is not bad per se. Humans get 90% of their sodium and chloride ions by the intake of table salt and in the right concentration salt has vital functions for our bodies:
- Sodium chloride regulates the water homeostasis and keeps the blood pressure up
- Sodium is essential for the conduction of stimuli via nerves
- Chloride is part of the gastric acid, which is important for our defense against pathogens in the stomach
Thus, consuming too less salt can indeed be dangerous. It can result in nausea, coma and even death (below 110 mmol/l sodium). However, these salt levels cannot possibly be reached by simply following a low-salt diet.
Jutta Löbert, who is a nutritional scientist in Munich, provided some useful tips on how to reduce salt intake and achieve a healthy and balanced diet. She explains that canned food contains a lot of salt, since salt is not only a flavor-enhancer, but also functions as a food preservative. “Everybody should be aware: the more processed food you buy and eat, the more salt you consume”, Löbert clarifies.
As an alternative, she recommends to do as much home cooking as possible, using fresh or frozen ingredients instead of canned food. As a rule-of-thumb, three quarters of the food on the plate should be of vegetable origin. “It’s best to use fresh, regional and seasonal groceries”, Löbert advises, “it’s fully mature in terms of taste and ingredients. You can not get better fruits and vegetables anywhere else.”
Other tips to reduce the salt intake are to use herbs, spices, juices or vinegar for taste refinement instead of salt. Mustard and ketchup, which are rich in salt, should be consumed only rarely. Löbert urges “to ban the salt shaker from the table”.
Generally, in a low salt diet, cured and salted meat and fish, including smoked meat as well as boiled and raw ham, should be excluded from the menu. Dry sausages, fish products as well as convenience food and especially canned food are forbidden, too.
Löbert recommends to consume products low in sodium and rich in potassium. Those are, for example, fruits and vegetables, either fresh or frozen, especially apricots, bananas, carrots, kohlrabi and tomatoes. The potassium content is even higher in concentrated foods, e.g. in tomato purée and dried fruits. Furthermore, potatoes, hazelnuts, cashews, almonds, peanuts, dark chocolate, flour made of spelt, rye and buckwheat are low in sodium and rich in potassium.
For a modern human being with a full-time job, it’s not always possible to cook fresh food on a daily basis and sometimes we just can’t sustain without convenience food. The good news here is that, at least in Germany, the amount of sodium has to be indicated on the packaging of convenience food since 2016. To inform yourselves about the sodium amount on the food you are buying, simply check the sodium content at the back of the packaging. Food low in sodium contains less than 0.12 g sodium in 100 g or 100 ml of the product. Products are considered sodium-free if they contain less than 0,005 g in 100 g or 100 ml of the product. By multiplying the amount of sodium by 2.54 you get the amount of table salt per 100 g or 100 ml of the product.
There is also no reason to deprive yourself of a good dinner in a restaurant when following a low-salt diet. It is possible to ask for a low-salt preparation and the sauce for a salad can easily be ordered separately. Ideally, you would ask for oil and vinegar instead of a convenience sauce.
Fascinatingly, the way we combine salt with other ingredients can play an important role in the effect of salt on our body. One example is the miso soup, which is a national Japanese dish rich in salt. The Japanese once feared that it could be banned because of its high salt content. However, an experiment showed that irrespective of the amount of miso soup consumed by the Japanese participants, the sodium excretion and blood pressure did not significantly change compared to the control group. Responsible for this effect is the combination of salt with soy beans — they contain isoflavones and other plant substances, which can minimize the effects of high salt.
Another interesting aspect of salt is that not all people react to it in the same way. One has to differentiate between salt-sensitive and salt-resistant people. It was believed that too much salt is bad for the blood pressure and could cause cardiovascular diseases. However, it was shown that not everybody benefited from a low-salt diet. Some people are resistant to salt and a low salt diet did not improve their blood pressure. Hence, more research is needed to investigate who benefits from a low salt diet and who does not and what factors are responsible for this effect. Nevertheless, since most of us don’t know if we belong to the salt-sensitive or salt-resistant group, following the recommendations to consume under 6 g of salt per day does no harm.
And a positive side effect of following a low-salt diet is the regeneration of the taste buds. High amounts of salt can blunt the taste buds but those can be regenerated by reducing the amounts of salt. Thus, a moderate-salt diet is probably not only good for our health, but will also teach you how to experience food anew, like a child does.
When Amanda first learned of her diagnosis, she did not consider diets or nutrition plans. In fact, her initial reaction was denial. “I didn’t want to do anything,” she admits. “So I ignored it.” But the support and encouragement from her husband brought her in contact with resources about living with MS and the lifestyle changes that could improve the quality of patient’s lives. Amanda felt empowered by the fact that there was something she could do to potentially impact the MS progression and to live a healthier life. So she decided to give it a try and focused on changing her diet. She stopped eating processed food, known to be packed with salt and saturated fat, and now “prepares everything from scratch”.
Changing the nutrition style gradually led to her feeling lighter and stronger. She also practices meditation daily, works out regularly and tries to spend a significant amount of time outdoors. She is also actively involved with the MS community in her local area in Ohio and was recently appointed a research committee member at iConquerMS, a nonprofit research network led by people with MS, bridging the gap between patients and researchers. The organization gathers information, such as health data, biosamples and knowledge, from the patients and shares it with multiple research facilities to advance the MS research.
But above all, Amanda now runs a blog, where she shares healthy recipes and lifestyle tips for fellow MS warriors — the term she uses to identify herself. “The disease can still hit you and knock you down. But being a warrior … means that you keep going and you don’t stop. You use everything, all the tools at your disposal, and just keep moving forward.”
Further reading/ References:
- Lerner et al. The World Incidence and Prevalence of Autoimmune Diseases is Increasing. International Journal of Celiac Disease, 2015
- Kleinewietfeld et al. Sodium chloride drives autoimmune disease by the induction of pathogenic Th17 cells. Nature, 2013
- Wu, Yosef and Thalhamer et al. Induction of pathogenic Th17 cells by inducible salt-sensing kinase SGK1. Nature, 2013
- Matthias et al. Sodium chloride is an ionic checkpoint for human Th2 cells and shapes the atopic skin microenvironment. Science Translational medicine, 2019
- Wilck et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature, 2017
- Ito et al. The Effects of the Habitual Consumption of Miso Soup on the Blood Pressure and Heart Rate of Japanese Adults: A Cross-sectional Study of a Health Examination. Internal medicine, 2017
Our authors are listed in an alphabetical order.
Individual contributions:
Elisabeth Huber interviewed Dr. Claudia Löffler and Ms. Jutta Löbert, and wrote chapter 3, on the nutritional plans and salt consumption.
Srivaishnavi Loganathan interviewed Prof. Dr. Christine Zielinski and wrote chapter 2, on the science behind salt and its effect on the immune system.
Barbara Safaric interviewed Dr. Krishnamoorthy, documented the personal story of Dr. Amanda Windhof (chapters 1 and 4), analysed the data and prepared the graphs on salt consumption and autoimmune disease epidemiology.
Kristina Popova and Srivaishnavi Loganathan interviewed Dr. Amanda Windhof.
All authors participated in the editing of the final piece and the headline preparation.
