Menthol-like cooling compounds, including (R)-(-)-carvone, inhibit the human bitter taste receptors for saccharin and acesulfame K.

G protein-coupled receptors (GPCRs) are responsible for sensing sweet, umami, and bitter tastes. Bitter taste receptors belong to the taste receptor type 2 (TAS2R) family, and although trigeminal stimulants, such as menthol, have been reported to reduce bitterness, little is known about whether and how they affect the function of TAS2R. Here, we report that some menthol-like cooling compounds, including (R)-(-)-carvone, act as inhibitors of TAS2R31 and TAS2R43, which are taste receptors responsible for the intrinsic bitter aftertaste of saccharin and acesulfame K. Since (R)-(-)-carvone only exerted a faint cooling effect and a cooling effect is often not preferred in food flavor design, this compound is expected to be highly effective in improving the unpleasant aftertaste of artificial sweeteners. Thus, this study not only provides novel insights into the mechanism by which trigeminal nerve stimulants improve the aftertaste of artificial sweeteners but also useful information for the flavor design of future food products containing artificial sweeteners.