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 EC50 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 IC50 values ranging from 10 to 50 μM, were identified.