A common food additive could alter metabolism in ways that could increase the risk of diabetes, a preliminary study suggests.
The study, which involved research in humans and mice, investigated a food additive called propionate, which prevents mold growth and is widely used as a preservative in cheeses, baked goods (including bread) and artificial flavorings.
The study found that, in mice, consumption of propionate led to high blood sugar levels in the short term and weight gain and insulin resistance in the long term. (Insulin resistance means the body doesn't respond well to the hormone insulin, which helps cells take in sugar, or glucose. Such resistance can lead to the high blood sugar levels seen in people with diabetes.)
In a small trial involving humans, people who consumed propionate experienced temporary increases in insulin resistance, over the space of a few hours, compared with those who didn't consume the additive.
However, this early research cannot prove that propionate causes diabetes. Larger studies conducted over longer periods are needed to better understand whether propionate contributes to diabetes in people, the authors said.
Still, the findings are concerning given how widely propionate is used, the authors wrote in their paper, published today (April 24) in the journal Science Translational Medicine. They called for more research into the potential metabolic effects of food components like propionate.
"Understanding how ingredients in food affect the body's metabolism at the molecular and cellular level could help us develop simple but effective measures to tackle the dual epidemics of obesity and diabetes," study senior author Dr. Gökhan Hotamisligil, a professor of genetics and metabolism at the Harvard T.H. Chan School of Public Health, said in a statement.
Propionate is "generally recognized as safe" by the U.S. Food and Drug Administration (FDA), meaning the ingredient doesn't need to be approved by the FDA to be added to food. It's also a naturally occuring fatty acid, produced by our gut bacteria when it breaks down fiber. But no one had investigated the metabolic effects of propionate when it's consumed as a food additive, the authors said.
In the new study, the researchers first gave propionate to mice, finding that the additive led to an increase in levels of several hormones. Those included glucagon (which tells the liver to release sugar into the bloodstream); norepinephrine (which is involved with blood pressure regulation and also raises blood sugar); and fatty acid-binding protein 4, or FABP4 (which is thought to be involved in fatty acid metabolism).
This surge in hormones led to hyperglycemia, or high blood glucose levels, in the mice.
When the researchers gave the mice water with low doses of propionate (similar to the concentrations found in preserved food) for 20 weeks, the animals gained more weight and showed increased insulin resistance, as compared with mice that didn't consume propionate.
Testing in people
To see how these findings translate to people, the researchers conducted a study involving 14 healthy, lean participants who didn't have diabetes. Participants were given a meal that contained either 1 gram of propionate (the amount typically found in a single meal of processed food) or a placebo. The subjects had samples of blood taken once before the meal and then at regular intervals after the meal for 4 hours.
One week later, the participants came back to the lab, and those who had originally received propionate received the placebo, and vice versa. (The study was "double blind," meaning that neither the researchers nor the participants knew which people were getting propionate versus the placebo.)
The study found that when people received propionate, they experienced an increase in hormone levels similar to those seen in the mouse studies. The propionate-receiving participants also showed increased levels of insulin and insulin resistance, compared with when they didn't receive the additive. Both groups had similar peaks in blood sugar levels after their meal, but those in the propionate group took slightly longer for their levels to return to baseline.
In a separate analysis, the researchers analyzed data from a previous weight-loss study involving 160 people, finding that blood levels of propionate were linked with insulin resistance. Specifically, the researchers found that larger declines in a person's propionate levels were tied to greater improvement in insulin resistance.
Still, that analysis found only an association and cannot prove that propionate causes insulin resistance or diabetes.
In addition, the human trial involved only healthy people of normal weight who did not have diabetes. So, more studies are needed to determine the effects of propionate on people who are obese and have diabetes, the authors said.
Some previous studies suggested that propionate and other fatty acids have beneficial effects when they are produced in our guts by bacteria as a byproduct of metabolism. But recent research suggests that propionate in foods doesn't have the same beneficial effects, the authors said. This may be because propionate has different effects depending on where it enters the body — when it's consumed in food, it has contact with cells much higher in the gasterointeinal tract than when it's produced by bacteria in the colon, the researchers noted in the study.