Small amounts of propionate, which is a common preservative found in food (particularly baked goods), can increase levels of blood glucose in humans, according to new research published in Science Translational Medicine. Amir Tirosh and colleagues found that just 1 g of calcium propionate (also known as E282) had a marked effect on the systemic level of key hormones, such as fatty acid-binding protein 4 (FABP4) and glucagon, in humans.
“This project stemmed from ongoing research on the metabolic actions of FABP4,” explains Tirosh. “We came across a paper from 1912 where the authors showed that administration of propionate to dogs resulted in increased glucose production.” Given the growing interest in this short-chain fatty acid, which is widely used as an ingredient in processed food, Tirosh and co-workers decided to repeat the 1912 study. “We wanted to investigate whether wild-type mice, FABP4-deficient mice and mice lacking hepatic glucagon receptor respond similarly to propionate,” adds Tirosh.
The team were able to replicate the findings from 1912 in wild-type mice, showing that treatment with oral propionate caused marked hyperglycaemia; however, by using FABP4-deficient mice and mice that lacked the hepatic glucagon receptor, they were able to study the differential contribution of FABP4 and glucagon to this hyperglycaemic response. “We found that propionate stimulated glycogenolysis and hyperglycaemia in mice by increasing plasma concentrations of noradrenaline, glucagon and FABP4,” adds Tirosh. “Furthermore, the hyperglycaemic response induced by propionate was dependent on FABP4.”
Next, Tirosh and colleagues studied the translational potential of their findings to human physiology in a small randomized, placebo-controlled, double-blinded study. They gave 14 lean healthy volunteers a meal with or without the addition of 1 g of calcium propionate (equivalent to 0.3% w/w, a common concentration used for the preservation of foods). The group collected blood samples before the participants ingested the meal and serial samples every 30 minutes for 4 hours after the meal had been eaten.
The authors found, just as they did in mice, that ingestion of propionate at levels similar to what is added to food for preservation increased plasma concentrations of noradrenaline, glucagon and FABP4, which in turn resulted in an increase in levels of blood glucose. “We were very surprised to find that even when a small amount of propionate was given to humans, it had a marked effect on the systemic concentration of these key hormones,” explains Tirosh. “Noradrenaline, glucagon and FABP4 normally act during fasting to protect against a dangerous drop in blood glucose; in this case, however, they are engaging inappropriately and increasing blood glucose.”
“ingestion of propionate at levels similar to what is added to food … resulted in an increase in levels of blood glucose”
Tirosh and colleagues are continuing their research into the molecular components of food. “Such studies could lead to the identification of other ingredients that could be hazardous, but also some that might be beneficial, to metabolic health,” concludes Tirosh.
Tirosh, A. et al. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci. Transl Med. 11, eaav0120 (2019)
About this article
Cite this article
Morris, A. Metabolic safety of common preservative under scrutiny. Nat Rev Endocrinol 15, 378 (2019). https://doi.org/10.1038/s41574-019-0217-3