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. Deidentified data that support the findings of this study are available on reasonable request to corresponding author.

中文翻译：

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食品防腐剂丙酸对人体葡萄糖代谢的急性影响

简介 丙酸 (PA) 是一种常见的食品防腐剂，通常被美国食品和药物管理局认为是安全的；然而，外源性 PA 对葡萄糖代谢的影响尚不完全清楚。我们的临床前研究表明，外源性 PA 会增加胰高血糖素、去甲肾上腺素和内源性葡萄糖生成 (EGP)。研究设计和方法 我们在 28 名健康男性和女性中进行了一项随机、安慰剂对照、交叉研究，以确定 PA（1500 毫克丙酸钙）对这些因素的影响。受试者进行了两次研究访问，每次访问之前都进行了 1 周的无 PA 饮食。在每次访问期间，葡萄糖、胰岛素、胰高血糖素、去甲肾上腺素、肾上腺素、在静息条件下（方案 1）和正常血糖（~85-90 mg/dL）或低血糖（~65-70 mg/dL）高胰岛素钳夹（方案 1）期间口服 PA/安慰剂后 2 小时评估 EGP 和 EGP 2）。结果与安慰剂相比，PA 显着增加：（1）方案 1 期间的胰高血糖素和去甲肾上腺素；(2) 方案 2 中正常血糖条件下的胰高血糖素、去甲肾上腺素和肾上腺素；(3) 方案 2 中低血糖条件下的去甲肾上腺素、肾上腺素和 EGP。结论 口服 PA 导致胰岛素反调节激素网络的不适当激活。这种不适当的刺激突出了 PA 作为潜在的代谢干扰物。支持本研究结果的去识别化数据可向通讯作者提出合理要求。