Pizza test reveals a weird link between diet and immune cells

You probably are aware of salt — the seasoning so iconic, it’s impossible to describe its taste without naming it.

And you probably know some best practices. Don’t eat instant Ramen every day — that’s a good way to overload on salt, and too much sodium (doctors will remind you) is linked to cardiovascular and other health problems. We also need some salt to live: It’s an electrolyte that helps regulate our body fluids.

That’s where the conventional wisdom often stops short. However, recent research suggests we have much more to learn.

According to research published on April 28 in the journal Circulation, this multidimensional mineral may play a bigger role than previously thought in another of our body’s crucial support systems: immunity.

With the help of one of America’s favorite salty foods, pizza, researchers in Germany found a unique way sodium can change the tiny structures deep within one class of immune cells, damaging their function temporarily.

It should be noted that though salt and sodium are often used interchangeably, they’re not the same: Sodium is the main ingredient of salt, but a measured amount of salt does not equal the same measure of sodium. Sodium is what enters the bloodstream when you eat something salty.

“What is interesting and new is that sodium is a powerful communicator with mitochondria with regards to blunting mitochondrial function,” Dominik Müller tells Inverse. Müller is the senior author of the study, a professor, and group leader of a lab at the Experimental and Clinical Research Center, part of the Max Delbrück Center for Molecular Medicine and the Charité Medical Faculty in Berlin.

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SCIENCE IN ACTION — Müller and colleagues knew from a previous study that sodium affected mitochondria but they didn’t know exactly how it worked.

Now, their research suggests even slightly elevated sodium levels changed the way monocytes (immune precursor cells) and macrophages (monocytes that migrate from the bloodstream into tissue) are fueled via mitochondria.

Critically, this reduction in energy produced in the mitochondria isn’t permanent. But it still disrupts the way immune cells typically function, implying that a diet heavy in salt could potentially drive inflammatory diseases.

To come to this conclusion, the study team treated macrophages extracted from mice and humans with sodium. A series of tests subsequently demonstrated that, in both mice and human cells, sodium stunted the mitochondria’s respiration — the process by which it makes energy.

The researchers moved on to testing the effects of dietary sodium on monocytes in real life, subjecting a group of male participants to a high-sodium diet over two weeks.

Participants took pills that added 6 grams of salt to their regular diets over the course of two weeks, which slightly elevated their blood sodium levels. Researchers found that, as the blood sodium levels rose, the oxygen consumption rate of monocytes decreased, suggesting impaired mitochondrial function.

After 14 more days, sodium levels went back to normal, and so did the immune cells.

The same stunting effect also happened after only a brief increase in blood sodium, delivered by way of pizza.

In another experiment, 10 men and 10 women ate a meal of pizza containing 10 grams of salt. The researchers noticed immediate decreases in mitochondrial function again. However, blood tests showed that eight hours after they ate the pizza, their mitochondria were back to normal.

“Just with this tiny change — this four millimoles change of sodium — you can somehow bother your mitochondria,” Müller says. “This was unexpected because huge loads of salt sometimes have artificial actions, but this is something that you can see upon one meal.”

HOW THIS AFFECTS LONGEVITY — Because the researchers only studied the effects of salt on this specific group of immune cells in the short term, there’s no definite consensus on the long-term effects of sodium.

In the short term, the cell changes they observed might actually help macrophages fight bacterial infections, the study team writes. These changes could also encourage inflammation that could lead to cardiovascular disease.

Complicating matters, sodium has been found to have varying effects on other kinds of immune cells. For example, previous research links increased dietary salt to a different kind of immune cell implicated in autoimmune diseases like multiple sclerosis or arthritis. On the other hand, sodium might also have a protective function by boosting an immune response under some conditions.

Whether or not there’s an inflammatory or anti-inflammatory effect appears to depend on the context. It may be too soon to tell if sodium’s temporary dampening of an important cell function would have lasting effects with a long-term diet of salty meals, over and over again.

Müller says he was relieved to see that the effects on the monocytes were reversible, at least in the short term. However, this significant connection between sodium and bacteria-fighting cells is one that merits more attention, he adds.

“One could envision that if you have the cycles of high salt situations, that you [would] often harm your mitochondrial energy production, but this needs to be tested in further studies,” Müller says.

In a worst-case scenario, a long-term, high-sodium diet could have some kind of “negative fitness” effect on the monocytes, but it’s still too early to know if that’s the case, he says.

WHY IT'S A HACK — In a world growing more accustomed to a Western diet that’s often high in sodium (along with protein, sugar, and fat), it can be difficult to avoid eating too much salt in one sitting and tempting to just accept your high-sodium fate.

But this study and others emphasize that high blood pressure isn’t the only side-effect of sodium-bombing our insides.

“Being aware of sodium intake is, in general, a good idea,” Müller says. “It might be that also on a cellular level, your mitochondrial function might appreciate this quite a lot.”

And there’s reason to expect the opposite might happen when you deprive your body of sodium for an extended stretch of time — for example, with intermittent fasting.

“Having 16 hours of no food means you would also have 16 hours of a no sodium challenge for your cells,” he says. “Is this a kind of decontamination of your cells, for at least a certain time?”

That question remains unanswered. When it comes to salt, there is still much to be learned —but the findings of this study suggest that there’s an evolutionary role for this cellular response to sodium.

Salt has varying effects on different parts of the body, and balance is key. “There is a yin and yang of this kind of mechanism,” Müller says. “It might be that it had some reason to exist and still to exist.”

HACK SCORE OUT OF 10 — 🍕🍕🍕/10 (too soon to tell)