Many drugs and phytochemicals are bitter, leading to noncompliance with prescriptions and avoidance of healthy foods and a need to suppress their taste. The goal of this study was to investigate the binding of bitterants (quinine and caffeine) by whey protein isolate (WPI) and the effect on perceived bitterness. Caffeine interacted minimally with WPI, while the proportion of unbound quinine decreased exponentially with protein concentration. Molecular modeling was used to show the energy of the quinine-Β-lactoglubulin interaction was an order of magnitude greater than the caffeine-Β-lactoglobulin interaction. Untrained assessors were used to assess the bitterness of caffeine (1.8, 5.7, and 18 mM) and quinine (0.056, 0.10, and 0.18 mM) solutions with 0% or 1% WPI. There was no significant effect of protein on the bitterness of caffeine solutions, but WPI decreased the bitterness of quinine relative to the same concentration in water. This is generally consistent with our hypothesis that higher binding results in lower bitterness; however the magnitude of reduction was not large and the bitterness of the protein-quinine solutions was greater than would be expected for the unbound quinine present.

The bulk vegetable oil–water partition coefficient of caffeine and quinine was determined by a shake‐flask method as log Kow = −1.32 and 2.97. These values were consistent with the effect of oil concentration on the distribution of the bitterants in an oil‐in‐water emulsion (0–2 and 0–20 wt% oil stabilized with 0.125 and 1 wt% whey protein isolate, respectively). For example, in a 20% o/w emulsion, approximately 90% of the total caffeine remained in the aqueous phase, whereas in a 2% o/w emulsion, only ∼20% of the quinine remained in the aqueous phase. The intensity of the bitter taste of caffeine and quinine in emulsions was assessed by a large cohort (n = 100) of untrained participants. An increase in fat in the emulsions (from 0.5 wt% to 2 wt% oil emulsions stabilized with 0.125 wt% whey protein isolate) caused a significant decrease in perceived bitterness that was accompanied by a decrease in the aqueous concentration of the hydrophobic bitterant quinine Specifically, the bitterness of quinine was reduced ∼13% in the o/w emulsion with more fat, and this drop paralleled a drop in the aqueous concentration and was generally consistent with aqueous dose–response functions published elsewhere. For the hydrophilic bitterant caffeine, there was no significant change in the perceived bitterness or aqueous concentration with changing oil concentration. We conclude that the perceived bitterness of a hydrophobic bitterant like quinine in an emulsion depends on the aqueous concentration rather than the overall concentration.