HMF causes anaphylactic symptoms by acting as a H₁ receptor agonist

5-Hydroxymethylfurfural (HMF) can readily form by acid-catalyzed transformations of various sugars such as fructose, sucrose and to a lesser degree glucose, and is known to widely exist in various sugar-containing consumer products. Thus the potential health effect of HMF has been a subject of intensive studies. There have been earlier reports of HMF's undesirable effects at or above high micromolar concentrations. In this study, HMF is found to stimulate the H₁ receptor in vivo and in vitro. When assessed in cell culture and animal models, HMF was found to cause deformation of in cell culture studies of HUVECs at 50 μM, to increase the vascular permeability of paw skin at 1.0 mg/mL, and trigger symptoms of anaphylaxis in animal models at 32.5 μg/kg. At the molecular level, HMF was found to induce the release of NO and related cytokines, and trigger H₁ receptor-mediated inflammatory responses. Mutation studies also suggest the binding sites for HMF on the H₁ receptor. The findings described suggest the need for close monitoring of HMF contents in consumer products and their related side effects.