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

Abstract

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.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

(A) Overview of study protocol. (B) Study visit timeline.

Figure 2

Effects of propionic acid (PA) vs. placebo on glucose (A), insulin (B), glucagon (C), norepinephrine (D), epinephrine (E), and endogenous glucose production (EGP) (F) during protocol 1. Mixed model analyses controlling for sex, BMI, age, time, and baseline value at T=120 minutes revealed: a significant effect of PA vs placebo on glucagon and norepinephrine and no significant effect of PA vs placebo on glucose, insulin, epinephrine, or EGP. Data reported as least squares means ± least squares standard error. Post-hoc, pairwise Wilcoxon test was used to compare responses with PA vs placebo at individual timepoints. *p

Figure 3

Effects of propionic acid (PA) vs placebo on glucose (A and B), insulin (C and D), glucagon (E and F), norepinephrine (G and H), epinephrine (I and J), and endogenous glucose production (EGP) (K and L) during euglycemic (left panels) and hypoglycemic (right panels) hyperinsulinemic clamp studies. During euglycemic clamp, PA as compared with placebo significantly increased glucagon, norepinephrine, and epinephrine but had no significant effect on EGP. During hypoglycemic clamp, PA as compared to placebo increased norepinephrine, epinephrine, and EGP, but had no significant effect on glucagon. Glucose is reported as observed means ± standard deviation and the mixed model analysis controls for time to determine the effect of PA vs placebo. Insulin, glucagon, norepinephrine, epinephrine, and EGP are reported as least squares means ± least squares standard error, and the mixed model analysis controls for sex, BMI, age, time, average blood glucose, and baseline value at T=300 minutes to determine the effect of PA vs placebo. Post-hoc, pairwise Wilcoxon test was used to compare responses between PA and placebo at individual timepoints. *p