Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
Scientists are looking at how salt affects our cells, and they're finding more reasons to avoid htoo much of it.
For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.
Blood Donated from Recovered Coronavirus Patients May Soon Yield a Stopgap Treatment
Antibodies from the blood of recovered patients is being tested as a stopgap treatment.
In October 1918, Lieutenant L.W. McGuire of the United States Navy sent a report to the American Journal of Public Health detailing a promising therapy that had already saved the lives of a number of officers suffering from pneumonia complications due to the Spanish influenza outbreak.
"These antibodies then become essentially drugs."
McGuire described how transfusions of blood from recovered patients – an idea which had first been trialed during a polio epidemic in 1916 – had led to rapid recovery in a series of severe pneumonia cases at a Naval Hospital in Massachusetts. "It is believed the serum has a decided influence in shortening the course of the disease, and lowering the mortality," he wrote.
Now more than a century on, this treatment – long forgotten in the western world - is once again coming to the fore during the current COVID-19 pandemic. With fatalities continuing to rise, and no vaccine expected for many months, experts are urging medical centers across the U.S. and Europe to initiate collaborations between critical care and transfusion services to offer this as an emergency treatment for those who need it most.
As of March 20, there are more than 90,000 individuals globally who have recovered from the disease. Some scientists believe that the blood of many of these people contains high levels of neutralizing antibodies that can kill the virus.
"These antibodies then become essentially drugs," said Arturo Casadevall, professor of Molecular Microbiology & Immunology at John Hopkins Bloomberg School of Public Health, who is currently co-ordinating a clinical trial of convalescent serum for COVID-19 involving 20 institutions across the US.
"We're talking about preparing a therapy right out of the serum of those that have recovered. It could also be used in patients who are already sick, but have not progressed to respiratory failure, to treat them before they enter intensive care units. That will provide a lot of support because there's a limited number of respirators and resources."
The first conclusive data on how the blood of recovered patients can help tackle COVID-19 is set to come out of China, where it was also used as an emergency treatment during the SARS and MERS outbreaks. On February 9, a severely ill patient in Wuhan was treated with convalescent serum and since then, hospitals across China have used the therapy on a total of 245 patients, with 91 reportedly showing an improvement in symptoms.
In China alone, more than 58,000 patients have now recovered from COVID-19. Casadevall said that last week the country shipped 90 tons of serum and plasma from these patients to Italy – the center of the pandemic in Europe – for emergency use.
Some of the first people to be treated are likely to be doctors and nurses in hospitals who are most at risk of exposure.
A current challenge, however, is that the blood donation from the recovered patients must be precisely timed in order to maximize the number of antibodies a future patient receives. Doctors in China say that obtaining the necessary blood samples at the right time is one of the major barriers to applying the treatment on a larger scale.
"It's difficult to get the donations," said Dr. Yuan Shi of Chongqing Medical University. "When patients have recovered from the disease, we would like to collect their blood two to four weeks afterwards. We try our best to call back the patients, but it's sometimes difficult to get them to come back within that time period."
Because of such hurdles, Japan's largest drugmaker, Takeda Pharmaceuticals, is now working to turn neutralizing antibodies from recovered COVID-19 patients into a standardized drug product. They hope to launch a clinical trial for this in the next few months.
In the U.S., Casadevall hopes blood transfusions from recovered patients can become clinically available as a therapy within the next four weeks, once regulatory approval has been received. Some of the first people to be treated are likely to be doctors and nurses in hospitals who are most at risk of exposure, to provide a protective boost in their immunity.
"A lot of healthcare workers in the U.S. have already been asked to quarantine, and you can imagine what effect that's going to have on the healthcare system," he said. "It can't take large numbers of people staying home; there's not the capacity."
But not all medical experts are convinced it's the way to go, especially when it comes to the most severe cases of COVID-19. "There's no knowing whether that treatment would be useful or not," warned Dr. Andrew Freedman, head of Cardiff University's School of Medicine in the U.K.
"There are going to be better things available in a few months, but we are facing, 'What do you do now?'"
However, Casadevall says that the treatment is not envisioned as a panacea to treating coronavirus, but simply a temporary measure which could give doctors some options until stronger options such as vaccines or new drugs are available.
"This is a stopgap option," he said. "There are going to be better things available in a few months, but we are facing, 'What do you do now?' The only thing we can offer severely ill people at the moment is respiratory support and oxygen, and we don't have anything to prevent those exposed from going on and getting ill."
Social distancing is a critical part of the strategy to defeat the novel coronavirus.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.