Widely-used food ingredient could increase risk for diabetes, obesity

Consumption of propionate, a food ingredient that's widely used in baked goods, animal feeds, and artificial flavorings, may increase the levels of several hormones associated with risk of obesity and diabetes, according to a new study led by researchers at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. The study published yesterday in the journal Science Translational Medicine.

The study, which combined data from a randomized placebo-controlled trial in humans and mouse studies, indicated that propionate can trigger a cascade of metabolic events that leads to insulin resistance and hyperinsulinemia, a condition marked by excessive levels of insulin. The findings also showed that in mice, chronic exposure to propionate resulted in weight gain and insulin resistance, according to the study abstract.

More than 400 million people worldwide suffer from diabetes, and the rate of diabetes incidence is projected to increase 40 percent by 2040 despite extensive efforts to curb the disease. The surging rates of diabetes, as well as obesity, in the last 50 years indicate that environmental and dietary factors must be influencing the growth of this epidemic. Researchers have suggested that dietary components including ingredients used for preparation or preservation of food may be a contributing factor, but there is little research evaluating these molecules.

For this study, the researchers focused on propionate, a naturally occurring short-chain fatty acid that helps prevents mold from forming on foods. They first administered this short chain fatty acid to mice and found that it rapidly activated the sympathetic nervous system, which led to a surge in hormones, including glucagon, norepinephrine, and a gluconeogenic hormone called fatty acid-binding protein 4 (FABP4). This led the mice to produce more glucose from their liver cells, leading to hyperglycemia, a defining trait of diabetes. The researchers found that chronic treatment of mice with a dose of propionate that was equivalent to the amount typically consumed by humans led to significant weight gain in the mice, as well as insulin resistance.

To determine how the findings in mice may translate to humans, the researchers established a double-blinded placebo-controlled study that included 14 healthy participants. The participants were randomized into two groups. One group received a meal that contained one gram of propionate as an additive and the other group was given a meal that contained a placebo. Blood samples were collected before the meal, within 15 minutes of eating the meal, and every 30 minutes thereafter for four hours.

The researchers found that people who consumed the meal containing propionate had significant increases in norepinephrine as well as increases in glucagon and FABP4 soon after eating the meal. The findings indicate that propionate may act as a "metabolic disruptor" that potentially increases the risk for diabetes and obesity in humans, researchers said.

The researchers noted that while propionate is generally recognized as safe by the U.S. Food and Drug Administration, these new findings warrant further investigation into propionate and potential alternatives that could be used in food preparation.