Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
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.
Scientists Just Created Liquid Solar Power That Can Be Stored for 18 Years
Look no further than this week's climate strikes for evidence that millions of people are passionate about curbing global warming.
Unlike relatively limited solar panel energy storage, norbornadiene can potentially maintain its potency for years.
But even potential solutions, like alternative meats, have their own challenges. Some scientists are putting their focus on the sun to help balance out our energy consumption.
In fact, they are gathering solar power so pure that, until recently, capturing it was an impossibility.
The Lowdown
A group of Swedish scientists has created a liquid called norbornadiene. This liquid sunshine can capture up to 30 percent of raw solar power. To put it in perspective, the best publicly available solar panels can harness 21 percent. Norbornadiene would bring in about 50 percent more power – a significant difference in energy efficiency.
Most notably, unlike relatively limited solar panel energy storage, norbornadiene can potentially maintain its potency for years. We could have the ability to collect and store premium solar power, making it easier for current and future generations to use fossil and nuclear fuel alternatives.
"The norbornadiene molecules that we have made have very good properties, in terms of solar energy capture efficiency, storage time and energy density," says team lead Dr. Kasper Moth-Poulson of the Chamlers University of Technology. "They can store energy without the need for insulation materials for 18 or more years."
Next Up
Swedish scientist Moth-Poulsen and his team have been testing the norbornadiene on the physics building roof at the Chalmers University of Technology. Once activated, it heats up to just below boiling and provides enough power to be useful.
The energy density is 250 watt-hours per kilogram, twice the strength of Tesla's popular Powerall battery.
It requires potentially toxic solvents, like a cobalt-based activator, to transform into its full potential. The team is currently trying to find less-hazardous catalysts to help transform the norbornadiene to its active form, quadricyclane. Exposing it to sunlight is the main way to reactivate the norbornadiene's power. Over time, scientists will likely make it more efficient with less toxic agents.
The energy density is 250 watt-hours per kilogram, twice the strength of Tesla's popular Powerall battery.
Open Questions
The biggest question is safety, perceived or otherwise: Are you ready to drive around with 250 kWh of pure solar in your Hyundai? Norbornadiene may be stable in a hermetically sealed lab, but sculpting it for everyday use requires another level of security.
The half-life of the sunshine power is also an estimate, too. The challenge with new scientific substances is you don't know how the matter will evolve over time. It is easy to be overly optimistic about this one discovery being the key to our energy needs. For the time being, it is wiser to look at norbornadiene as a progressive step rather than a revolutionary one.
Even at its least effective, norbornadiene and its related material is a step toward us utilizing the one natural resource that won't run out for generations. In the short-term, a stable form of it could offset our fossil and nuclear fuel use and even help lower the carbon footprint made by long-distance transportation. It will be fascinating to see what future aircraft builders, home designers and even car manufacturers do as the solar technology conversation heats up.
Moth-Poulsen wants norbornadiene to be a definitive part of the climate change puzzle.
"I hope that in five years, we will see the first products based on our molecules and could help mitigate the daily variations in temperature," he says. "This will lead to increased thermal comfort and reduced energy consumption for heating and cooling."
Virtual Reality is Making Medical Care for Kids Less Scary and Painful
A blood draw is not normally a fun experience, but these days, virtual reality technology is changing that.
Instead of watching a needle go into his arm, a child wearing a VR headset at Children's Hospital Los Angeles can play a game throwing balls at cartoon bears. In Seattle, at the University of Washington, a burn patient can immerse herself in a soothing snow scene. And at the University of Miami Hospital, a five-minute skin biopsy can become an exciting ride at an amusement park.
VR is transforming once-frightening medical encounters for kids, from blood draws to biopsies to pre-surgical prep, into tolerable ones.
It's literally a game changer, says pediatric neurosurgeon Kurtis Auguste, who uses the tool to help explain pending operations to his young patients and their families. The virtual reality 3-D portrait of their brain is recreated from an MRI, originally to help plan the surgery. The image of normally bland tissue is painted with false colors to better see the boundaries and anomalies of each component. It can be rotated, viewed from every possible angle, zoomed in and out; incisions can be made and likely results anticipated. Auguste has extended its use to patients and families.
"The moment you put these headsets on the kids, we immediately have a link, because honestly, this is how they communicate with each other," says Auguste. "We're all sitting around the table playing games. It's really bridged the distance between me, the pediatric specialist, and my patients" at the Benioff Children's Hospital Oakland, now affiliated with the University of California San Francisco School of Medicine.
The VR experience engages people where they are, immersing them in the environment rather than lecturing them. And it seems to work in all environments, across age and cultural differences, leading to a better grasp of what will be undertaken. That understanding is crucial to meaningful informed consent for surgery. It is particularly relevant for safety-net hospitals, which includes most children's hospitals, because often members of the families were born elsewhere and may have limited understanding of English, not to mention advanced medicine.
Targeting pain
"We're trying to target ways that we can decrease pain, anxiety, fear – what people usually experience as a function of a needle," says Jeffrey Gold, a pioneer in adapting VR at Children's Hospital Los Angeles. He ran the pain clinic there and in 2004 initially focused on phlebotomy, simple blood draws. Many of their kids require frequent blood draws to monitor serious chronic conditions such as diabetes, HIV infection, sickle cell disease, and other conditions that affect the heart, liver, kidneys and other organs.
The scientific explanation of how VR works for pain relief draws upon two basic principles of brain function. The first is "top down inhibition," Gold explains. "We all have the inherent capacity to turn down signals once we determine that signal is no longer harmful, dangerous, hurtful, etc. That's how our brain operates on purpose. It's not just a distraction, it's actually your brain stopping the pain signal at the spinal cord before it can fire all the way up to the frontal lobe."
Second is the analgesic effect from endorphins. "If you're in a gaming environment, and you're having fun and you're laughing and giggling, you are actually releasing endorphins...a neurochemical reaction at the synaptic level of the brain," he says.
Part of what makes VR effective is "what's called a cognitive load, where you have to actually learn something and do something," says Gold. He has worked with developers on a game call Bear Blast, which has proven to be effective in a clinical trial for mitigating pain. But he emphasizes, it is not a one-size-fits all; the programs and patients need to be evaluated to understand what works best for each case.
Gold was a bit surprised to find that VR "actually facilitates quicker blood draws," because the staff doesn't have to manage the kids' anxiety, so "they require fewer needle sticks." The kids, parents, and staff were all having a good time, "and that's a big win when everybody is benefiting." About two years ago the hospital made VR an option that patients can request in the phlebotomy lab, and about half of kids age 4 and older choose to do so.
The technology "gets the kids engaged and performing the activity the way we want them to" to maximize recovery.
VR reduces or eliminates the need to use sedation or anesthesia, which carries a small but real risk of an adverse reaction. And important to parents, it eliminates the recovery time from using sedation, which shortens the visit and time missed from school and work.
A more intriguing question is whether reducing fear and anxiety in early-life experiences with the healthcare system through activities like VR will have a long-term affect on kids' attitudes toward medicine as they grow older. "If you're a screaming meemie when you come get your blood draw when you're five or seven, you're still that anxious adolescent or adult who is all quivering and sweating and avoiding healthcare," Gold says. "That's a longitudinal health outcome I'd love to get my hands on in 10-15 years from now."
Broader applications
Dermatologist Hadar Lev-Tov read about the use of VR to treat pain and decided to try it in his practice at the University of Miami Hospital. He thought, "OK, this is low risk, it's easy to do. So we got some equipment and got it done." It was so affordable he paid for it out of his own pocket, rather than wait to go through administrative channels. The results were so interesting that he decided to publish it as a series of case studies with a wide variety of patients and types of procedures.
Some of them, such as freezing off warts, are not particularly painful. "But there can be a lot of anxiety, especially for kids, which can be worse than pain and can disrupt the procedure." It can trigger a non-rational, primal fight or flight response in the limbic region of the brain.
Adults understand the need for a biopsy of a skin growth and tolerate what might be a momentary flick of pain. "But for a kid you think twice about a biopsy, both because it's a hassle and because it could be a traumatic event for a child," says Lev-Tov. VR has helped to allay such fears and improve medical care.
Integrating VR into practice has been relatively easy, primarily focusing on simple training for staff and ensuring that standard infection control practices are used in handling equipment that is used by different patients. More mundane issues are ensuring that the play back and wi-fi equipment are functioning properly. He has had a few complaints from kids when the procedure is competed and the VR is turned off prematurely, which is why he favors programs like a roller coaster ride that lasts about five minutes, ample time to take a biopsy or two.
The future is today
The pediatric neurosurgeon Auguste is collaborating with colleagues at Oakland Children's to expand use of VR into different areas of care. Cancer specialists often use a port, a bubble installed under the skin in the chest of the child, to administer chemotherapy. But the young patient's curiosity often draws their attention downward to the port and their chin can potentially contaminate or obstruct it, interfering with the procedure. So the team developed a VR game involving birds that requires players to move their heads upward, away from the port, improving administration of the drugs and reducing the risk of infection.
Innovative use of VR just may be one tool that actually makes kids eager to visit the doctor.
Other games are being developed for rehabilitation that require the use of specific nerve and muscle combinations. The technology "gets the kids engaged and performing the activity the way we want them to" to maximize recovery, Auguste explains. "We can monitor their progress by the score on the game, and if it plateaus, maybe switch to another game."
Another project is trying to ease the anxiety and confusion of the patient and family experience within the hospital itself. Hospital staff are creating a personalized VR introductory walking tour that leads from the parking garage through the maze of structures and corridors in the hospital complex to Dr. Auguste's office, phlebotomy, the MRI site, and other locations they might visit. The goal is to make them familiar with key landmarks before they even set foot in the facility. "So when they come the day of the visit they have already taken that exact same path, hopefully more than once."
"They don't miss their MRI appointment and therefore they don't miss their clinical appointment with me," says Auguste. It reduces patient anxiety about the encounter and from the hospital's perspective, it will reduce costs of missed and rescheduled visits simply because patients did not go to the right place at the right time.
The VR visit will be emailed to patients ahead of time and they can watch it on a smartphone installed in a disposable cardboard viewer. Oakland Children's hopes to have the system in place by early next year. Auguste says their goal in using VR, like other health care providers across the country, is "to streamline the entire patient experience."
Innovative use of VR just may be one tool that actually makes kids eager to visit the doctor. That would be a boon to kids, parents, and the health of America.