“The study also raises a larger question - should other individual nutrient molecules in foods —not just additives — get a closer look as well,” said one of the study's authors, Dr Gökhan S Hotamlgil, James Stevens Simmons professor of genetics and metabolism, and director, Sabri Ülker Centre for Metabolic Research at Harvard T H Chan School of Public Health.

Fast facts about propionate
What is it: “Propionate, or propionic acid, is a commonly used food preservative. Propionate is not foreign to the human body. It exists naturally in the gut, and some studies have even shown that it may be beneficial,” said Dr Hotamlgil. It is unclear why, or if, propionate produces a different response when it occurs naturally compared with when it is consumed as a food additive.

How it is used: Manufacturers add propionate to many different products, including bread, animal feed, frosting, pudding, jams and jellies, and cheese, to prevent the growth of mold. The FDA currently considers it safe to use as a food additive.

How to find it: It often appears on food labels as calcium propionate.
What is new: This study found that propionate, when eaten as part of the diet, might boost the body’s production of blood sugar, which could increase the risk of diabetes and obesity.

What is next: More study is needed to confirm these findings.

What is in the food you are eating?
“There are thousands of unique molecules present in our daily diets, and this study teaches us that it may be prudent to look at these ingredients more carefully,” said Dr Hotamlgil.

“The long-term metabolic effects of many of these chemicals are largely unknown, even though people are already eating them on a regular basis. Even a simple molecule can produce dramatic effects inside the body,” he added.

Studying the body's response
Dr Hotamlgil said he and his team came to study propionate because of their interest in another fatty protein that interacts with lipids, called fatty acid–binding protein 4 (FABP4).

FABP4 plays a role in glucose production in the body. When the scientists gave propionate to mice, it triggered a metabolic chain reaction. First, it appeared to set off a nervous system response, which then prompted a rise in blood levels of FABP4 and a critical hormone called glucagon.

FABP4 and glucagon have an important job in the body, which is essentially the opposite of insulin's role. The body makes insulin to bring down high glucose levels in the blood. FABP4 and glucagon spur your liver to produce more glucose when one’s blood level drops. A very low blood glucose level (hypoglycemia) can be life-threatening.

But, in the mouse experiment, propionate kicked FABP4 and glucagon into action while glucose levels were still in the normal range. The mice's bodies produced more glucose in response to the propionate when it wasn’t needed.

This boosted blood sugar levels higher than they should have been, a condition called hyperglycemia, which is similar to what occurs when people have diabetes.

When the mice were given propionate over time, they not only gained a weight, but also started to experience insulin resistance, a condition in which the body’s cells have trouble responding properly to insulin and absorbing glucose from the bloodstream.

“The other interesting thing is that this relationship was totally dependent on the production of FABP4 and glucagon. When those were blocked, propionic acid didn’t produce the same response,” said Dr Hotamlgil.

Do the findings apply to people?
This finding raised another question: does propionate only affect mice, or would the same response occur in people too?

Researchers tested 14 healthy people, giving half of them 1g of propionate and the other half a placebo.

They chose that amount because it is similar to what people would normally eat in food. They took a blood sample from the recruits before they ate, 15 minutes after they ate, and then every 30 minutes for the next four hours.

Like the mice, the people who consumed propionate had the same hormone surge shortly after they ate, which indicated that humans may very well experience the same worrisome metabolic effects as the mice did.

“But the study was very small, so we cannot make strong claims,” said Dr Hotamlgil, adding, “Still, it illustrates the need to study propionate further.”

An upward trend in obesity
This study is not the only indication that propionate may be a problem.

“I think the interesting thing is that the use of propionic acid has increased over time, quite dramatically. It actually does overlap with the time where there was a great rise in obesity and metabolic disease,” said Dr Hotamlgil.

This increase in diabetes and obesity has occurred over roughly the past 50 years, and some scientists have suspected that something in the environment or in the diet may be helping to drive the increase.

“And those numbers are still going up. Some 400 million people around the world already have diabetes, and that number is expected to increase by 40 per cent in the next two decades,” according to the study's authors.

“We are not claiming that we have now explained this phenomenon,” said Dr Hotamlgil.

“To determine whether propionate has played a role in that rise, researchers will need to conduct a more comprehensive human study with a greater number of subjects and longer durations of exposure,” he added.

Should one change his/her diet?
Until scientists uncover more answers, it is too soon to make recommendations that people avoid propionate or that the preservative be removed from the food supply.

“But it strongly suggests that this, as well as many other ingredients, should be on our radar. If larger and longer human study supports the findings, it would be a very simple intervention,” said Dr Hotamlgil.

There are numerous food preservatives that could be used instead of propionate, so switching it out would be relatively easy.

In the future, Dr Hotamlgil says his team plans to study more food ingredients, not just additives, to better understand how they interact with the human body on a biological level to influence health.