High Sodium Impacts Mitochondrial Respiration

According to a paper published in Circulation yesterday, too much salt can severely disrupt the energy balance in immune cells and stop them from working properly.

Five years ago, researchers found that elevated sodium concentrations in the blood affect both the activation and the function of patrolling monocytes, which are the precursors to macrophages. "But we didn't know exactly what was happening in the cells," says Dr. Sabrina Geisberger of the Berlin Institute for Medical Systems Biology, lead author of the current study.

The team began their work looking at the metabolism of immune cells that had been exposed to high salt concentrations. Changes appeared after just three hours. "It disrupts the respiratory chain, causing the cells to produce less ATP and consume less oxygen," explains Geisberger. "Salt very specifically inhibits complex II in the respiratory chain," she adds.

This has consequences: The lack of energy causes the monocytes to mature differently. "The phagocytes, whose task is to identify and eliminate pathogens in the body, were able to fight off infections more effectively. But this could also promote inflammation, which might increase cardiovascular risk," explains senior author Professor Dominik Müller.

The team then conducted a study in which healthy male participants supplemented their usual diets with six grams of salt in tablet form every day for 14 days. In another clinical study, the researchers investigated had participants eat take-out pizza. They then analyzed the monocytes in the participants' blood. The findings showed that the dampening effect on mitochondria doesn't just occur after an extended period of increased salt intake—it also happens after a single pizza. Data from the pizza experiment showed the effect was not long lasting: Blood was taken from the participants after three and eight hours, and the effect was barely measurable in the second sample.

"That's a good thing. If it had been a prolonged disturbance, we'd be worried about the cells not getting enough energy for a long time," says Müller. The mitochondrial activity is therefore not permanently inhibited. That said, the continuous risk of sodium on mitochondrial function if a person eats very salty food several times a day cannot be ruled out, but needs to be tested in the future.

"The fundamental finding of our study is that a molecule as small as the sodium ion can be extremely efficient at inhibiting an enzyme that plays a crucial role in the respiratory chain," says Kempa. "When these ions flood into the mitochondria—and they do this under a variety of physiological conditions—they regulate the central part of the electron transport chain." It therefore appears to be a very fundamental regulatory mechanism in cells.