Food additives are a mainstay of Western diets. New research shows how a commonly used anti-mold agent alters sugar metabolism and drives insulin resistance in mice and men.
Eating a Western diet, high in processed foods, sugar, and fat, is a known risk factor for obesity and type 2 diabetes.
Avoiding processed foods is actually not that easy. Preservatives, which keep our food fresh for longer, lurk in many places.
One such chemical is the anti-mold agent propionate, a short-chain fatty acid that the bacteria in our gut produce naturally. As a preservative, its other name is E282, and it features as a common food additive in bread and other baked goods.
According to the Codex Alimentarius, the international food standards guide by the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations, propionate may be added to a host of other things, including breakfast cereals, dairy- and egg-based deserts, sausage casings, processed cheese, and sports drinks.
Researchers from Harvard T.H. Chan School of Public Health, in Boston, MA, along with colleagues at the Sheba Medical Center, in Ramat Gan, Israel, and others, made a surprising discovery when they studied the effects of propionate in mice and humans.
The team recently published their findings in the journal Science Translational Medicine.
Propionate leads to high blood sugar in mice
Dr. Amir Tirosh, an associate professor of medicine at Tel-Aviv University's Sackler Faculty of Medicine and director of the Institute of Endocrinology at Sheba Medical Center, told Medical News Today that he had initially set out to study the actions of fatty acid-binding protein 4 (FABP4), which researchers think plays a role in sugar and fat metabolism.
"We incidentally came across an old scientific paper from 1912 demonstrating that administration of propionate to dogs resulted in increased glucose production," he explained.
To study the connection between propionate and FABP4, Dr. Tirosh and the team gave healthy, nonobese mice a dose of the preservative. As in the dogs, the team found that blood sugar levels rose.
The question is: How does propionate work to achieve this?
The researchers found that propionate activated the sympathetic nervous system, as measured by levels of norepinephrine, and increased the levels of the hormones glucagon and FABP4. This caused the liver to produce high levels of glucose, which in turn led to high levels of insulin in the blood.
"Normally, these hormones act during fasting to protect against a dangerous drop in blood glucose," Dr. Tirosh explained. "In this case, they are engaging without such a threat and increasing blood glucose."
The mice were then fed a low dose of between 0.15 and 0.3 percent propionate in their diet over several weeks. This is equivalent to how much a person eating a Western diet would consume.
As a result, the mice developed higher levels of glucagon and FABP4, high levels of blood insulin, and insulin resistance — a hallmark of type 2 diabetes. They also put on more weight, with a significant increase in fat mass, compared with the mice receiving a standard diet.
Propionate disrupts metabolism in humans
Next, Dr. Tirosh and his colleagues recruited 14 healthy, nonobese volunteers.
"This propionate dose of 1 g is equivalent to the most commonly used amount of 0.3% [...] to which humans are exposed when consuming a single processed food–based meal," the study authors explain.
After 2 weeks, the same participants returned, and the groups were switched, meaning that the volunteers who were in the placebo group during the first visit ate the propionate-containing meal during the second visit.
As with the mice, the study participants experienced spikes of norepinephrine, glucagon, and FABP4, increased blood insulin levels, and reduced insulin sensitivity.
"We were very surprised to see that even when [a] small amount of propionate was given to humans, [it] had significant effects on the systemic level of key hormones such as FABP4," Dr. Tirosh commented.
Finally, the research team analyzed data from 160 participants of the Dietary Intervention Randomized Controlled Trial, known as DIRECT, to see if propionate levels and weight loss were connected.
At the start of the study, the team found a link between levels of propionate and insulin resistance. After 6 months, lower levels of propionate showed an association with more significant improvements in insulin sensitivity.
Study 'one piece of the puzzle'
Dr. Tirosh acknowledges that the study's limitations include that fact that he was unable to show cause and effect of propionate consumption on global obesity and type 2 diabetes. The team also did not study the long-term effects of chronic, low-level propionate exposure in humans.
MNT asked Dr. Tirosh if he would recommend that people avoid propionate in their diet.
"It will be premature to do so based on a single study. Therefore, we are not making such recommendations," he explained. "Our research should serve as a proof-of-principle for the potential interference of propionate in normal metabolism, but most of the data was obtained in mice, and we need to be careful when translating these findings to humans."
"We see our findings as one piece of the puzzle," Dr. Tirosh explained.
Meanwhile, the team's research efforts continue, with a focus on how preservatives, artificial sweeteners, and other natural ingredients might affect our metabolism.
"Given the epidemic proportion of obesity and diabetes, there is a need, in our view, to extensively assess the potential long-term metabolic effects of many environmental factors that have changed over the past few decades, both for their potential harmful and useful effects."
Dr. Amir Tirosh