Characterization and Modulation of the Bitterness of Polymethoxyflavones Using Sensory and Receptor-Based Methods

An obstacle in the application of many “health ingredients” is their alleged off-flavor. We used a combination of chemical, sensory, and biological analyses to identify the bitter components in citrus peel-derived polymethoxyflavone preparations, claimed to be functional in the lowering of cholesterol. Nobiletin (56–81%) and tangeretin (10–33%) were found to be the main bitter components. Using in vitro receptor assays, hTAS2R14 was shown to be the main bitter receptor involved in their perception, with EC<sub>50</sub> values of 14 and 63 μM, respectively. Our analysis provided several routes for off-flavor reduction. Purification is an option because a purified, single PMF species proved to be considerably less bitter upon application in emulsified foods, due to limited solubility in the aqueous phase. A second route, also demonstrated in vivo, is C5-specific demethoxylation, in line with the finding that 5-desmethylnobiletin does not activate hTAS2R14. A third route could be the use of TAS2R14 antagonists. As a proof of principle, several antagonists, with IC<sub>50</sub> values ranging from 10 to 50 μM, were identified.