Photo: Kris Connor (Getty Images)

In recent years, scientists have started cautiously warning about the subtle harms that certain food additives might be causing in people. A new study out Wednesday suggests that the common food preservative propionate could be one of these additives to be worried about. In experiments in both mice and people, it found eating propionate could negatively affect metabolism, including raising resistance to insulin.

Propionate, or propionic acid, is a ubiquitous part of our world. It’s naturally produced by many bacteria, including those that live inside our gut and skin. It’s also added to animal feed and human foods like cheese, baked goods, and artificial flavorings as a preservative. But though propionate is one of many additives on the Food and Drug Administration’s generally recognized as safe to eat (GRAS) list, there’s been some research indicating that propionate isn’t totally innocuous in the body.

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In animals, for example, it’s thought that propionate can raise blood sugar levels via the liver, which converts glucose from non-carb sources of fuel. This ability is even used by species of plant-eating ruminants, like cows, to regulate healthy blood sugar levels. In humans, the relationship with propionate is more mysterious. Some studies have suggested that propionate and other short-chain fatty acids naturally produced by the body’s gut bacteria can actually help us maintain a healthy metabolism, suppress appetite, and reduce the risk of obesity. But other studies have suggested that people who have more propionate in their system are more likely to be obese.

To better get a handle on the short-term effects of propionate consumed from food, the authors of this current study, published in Science Translational Medicine, did feeding experiments with both mice and people. The human portion of the study was a randomized, placebo-controlled, double-blinded trial with 14 healthy volunteers.

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“We verified that in mice, it does lead to a surge of blood glucose. But the most interesting thing we determined in these experiments is that a single dose of propionate can increase the hormones in the body that are designed to stimulate glucose production from the liver,” study author Gökhan S. Hotamışlıgil, director of the Sabri Ülker Center for Nutrient, Genetic and Metabolic Research at Harvard’s T.H. Chan School of Public Health, told Gizmodo. “There are times when that’s needed, like when you’re starving or have dangerously low blood sugar. But here, it was almost tricking the body into thinking that it needs to produce glucose when it doesn’t.”

And in people, these higher levels of hormones also seemed to cause insulin resistance, meaning their bodies didn’t respond as well to insulin’s signal to lower blood sugar. Over time, chronic insulin resistance is known to help contribute to type 2 diabetes and other metabolic disorders like obesity.

In the mouse experiments, mice that were fed low doses of propionate for long periods of time also gradually gained more weight than mice that did not consume propionate. But Hotamışlıgil and his team aren’t saying that their findings should immediately make someone avoid cheese and bread.

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“We’re reluctant to make giant claims and recommendations right now,” he said. “This is a proof-of-principle study just illustrating that we can actually identify these molecules and study their biology, which will then stimulate further work.”

For now, Hotamışlıgil added, there needs to be more research deciphering how exactly propionate might be causing these metabolic changes. In people, for instance, they found evidence that propionate’s effects are happening via the brain and nervous system through the production of adrenaline rather than by directly influencing the digestive system or liver. That research will need to include human studies with lots more volunteers from different labs.

Regardless of what Hotamışlıgil and other scientists end up discovering about propionate, he sees a silver lining in studies like this that are trying to suss out the more nuanced nutritional effects of foods.

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“I think in the 21st century, we can actually approach diet and nutrition and food with a very different lens than we did a century ago. Now we have tools that can let us study in detail, on a molecular level, not only the harmful things—because usually, people are interested in the harmful things—but the useful things in our food,” he said. “Some of those harmful things we can then very easily eliminate from our food preparation or reduce our exposure to, and that could have tremendous impacts on our health.”