Acute effects of the food preservative propionic acid on glucose metabolism in humans

BMJ Open Diabetes Res Care. 2021 Jul;9(1):e002336. doi: 10.1136/bmjdrc-2021-002336.


Introduction: Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose metabolism that are not fully understood. Our preclinical studies demonstrated exogenous PA increases glucagon, norepinephrine, and endogenous glucose production (EGP).

Research design and methods: We performed a randomized, placebo-controlled, crossover study in 28 healthy men and women to determine the effect of PA (1500 mg calcium propionate) on these factors. Subjects had two study visits, each preceded by a 1 week, PA-free diet. During each visit, glucose, insulin, glucagon, norepinephrine, epinephrine, and EGP were assessed for 2 hours after oral administration of PA/placebo under resting conditions (protocol 1) and during either a euglycemic (~85-90 mg/dL) or hypoglycemic (~65-70 mg/dL) hyperinsulinemic clamp (protocol 2).

Results: PA, as compared with placebo, significantly increased: (1) glucagon and norepinephrine during protocol 1; (2) glucagon, norepinephrine, and epinephrine under euglycemic conditions in protocol 2; and (3) norepinephrine, epinephrine, and EGP under hypoglycemic conditions in protocol 2.

Conclusion: Oral consumption of PA leads to inappropriate activation of the insulin counterregulatory hormonal network. This inappropriate stimulation highlights PA as a potential metabolic disruptor.

Keywords: catecholamines; endogenous glucose production; food safety; glucagon.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose*
  • Cross-Over Studies
  • Female
  • Food Preservatives*
  • Glucose
  • Glucose Clamp Technique
  • Humans
  • Male
  • Propionates
  • United States


  • Blood Glucose
  • Food Preservatives
  • Propionates
  • Glucose
  • propionic acid