The Influence of Sodium Salts on Binary Mixtures of Bitter-tasting Compounds

Chem. Senses 29: 431–439, 2004 DOI: 10.1093/chemse/bjh045 The Influence of Sodium Salts on Binary Mixtures of Bitter-tasting Compounds Russell S.J. Keast, Thomas M. Canty and Paul A.S. Breslin Monell Chemical Senses Center, 3500 Market St, Philadelphia, PA 19104, USA Correspondence to be sent to: Russell Keast, Faculty of Applied Sciences, RMIT University, GPO Box 2476V, Melbourne, 3001, Australia. E-mail: Abstract In order to study potential mixture interactions among bitter compounds, selected sodium salts were added to five compounds presented either alone or as binary bitter-compound mixtures. Each compound was tested at a concentration that elicited ‘weak’ perceived bitterness. The bitter compounds were mixed at these concentrations to form a subset of possible binary mixtures. For comparison, the concentration of each solitary compound was doubled to measure bitterness inhibition at the higher intensity level elicited by the mixtures. The following sodium salts were tested for bitterness inhibition: 100 mM sodium chloride (salty), 100 mM sodium gluconate (salty), 100 and 20 mM monosodium glutamate (umami), and 50 mM adenosine monophosphate disodium salt (umami). Sucrose (sweet) was also employed as a bitterness suppressor. The sodium salts differentially suppressed the bitterness of compounds and their binary combinations. Although most bitter compounds were suppressed, the bitterness of tetralone was not suppressed, nor was the bitterness of the binary mixtures that contained it. In general, the percent suppression of binary mixtures of compounds was predicted by the average percent suppression of its two components. Within the constraints of the present study, the bitterness of mixtures was suppressed by sodium salts and sucrose independently, with few bitter interactions. This is consistent with observations that the bitter taste system integrates the bitterness of multi-compound solutions linearly. Key words: binary mixtures, bitterness inhibition/supression, bitter taste, sodium salts, taste psychophysics Introduction Everyday life exposes us to complex mixtures of bitter tasting compounds. For example, many foods contain multiple compounds that can elicit bitterness (e.g. catechin, theophylline, theobromine, and caffeine in black tea). Similarly, Over-The-Counter pharmaceuticals are often codelivered within a formulation (e.g. dextromethorphan, acetaminophen, and pseudoephedrine in cough syrups). Despite the potential for interactions via the cellular complexity of the bitter taste system [multiple G-proteincoupled receptors and post-receptor transduction mechanisms (Kinnamon and Margolskee, 1996; Wong et al., 1996; Rossler et al., 1998; Huang et al., 1999; Adler et al., 2000; Chandrashekar et al., 2000)], bitterness perception often appears additive when compounds are mixed in binary combination (Keast et al., 2003). For example, adding a weakly bitter alkaloid (e.g. quinine–HCl) to a weakly bitter amino acid (e.g. L-tryptophan) results in a final bitterness that is equal to the addition of the weakly bitter alkaloid to itself, or the weakly bitter amino acid to itself (see Figure 1, Equation 4). Therefore, the processes of increasing concentration and mixing together different compounds are related to each other in that they produce similar levels of perceived bitter taste intensity. We investigated the influence of bitterness suppression on binary mixtures of bitter compounds as yet another test of binary bitter mixture interactions. If the suppression of the individual compounds predicts the suppression of bitter mixtures, then there is little evidence of interactions. When bitter compounds are mixed together, the combination solution appears more bitter than either compound would alone. This creates the opportunity for the mixture to appear more difficult to suppress than its components. Because bitterness is more difficult to suppress as perceived intensity increases (Breslin and Beauchamp, 1995), we employed the additional comparison condition of adding salts to individual bitter compounds at double their respective concentrations in the binary mixtures. There are few known bitterness inhibitors, but sodium (Na+) salts have been shown to suppress the bitterness of certain compounds in human psychophysical studies (Bartoshuk and Seibyl, 1982; Breslin and Beauchamp, 1995; Keast and Breslin, 2002a,b). This suppression is mainly an oral peripheral effect of ions (at the cellular/epithelial level) rather than a cognitive effect (central process) of the perceived taste. To demonstrate the peripheral effect, Kroeze and Bartoshuk (1985) applied a bitter stimulus to Chemical Senses vol. 29 no. 5 © Oxford University Press 2004; all rights reserved. 432 R.S.J. Keast, T.M. Canty and P.A.S. Breslin Figure 1 Schematic design of this study. Each equation is a hypothetical example of what happens to the bitterness intensity of compounds A and B when they are mixed together and/or a sodium salt is added. Equation 1 shows that a mixture of A + B has a bitter intensity of gLMS 12 (general Labeled Magnitude Scale). When a sodium salt is added to the mixture, the bitterness intensity is reduced to gLMS 6. Equations 2 and 3 show the bitterness of the individual components of the mixture, A and B (both gLMS 8), and the bitterness of each component after a sodium salt has been added (A gLMS 6, B gLMS 1). Equation 4 (box) illustrates that doubling the concentration of bitter compounds and mixing together their components are related to each other in that they produce similar levels of perceived bitter taste intensity, if the components are equally intense initially (Keast et al., 2003). Equations 5 and 6 use the model in Equation 4 to assess the bitterness suppression of the mixture components, A and B, at double their concentration at which each component has the same intensity as the mix A + B, gLMS 12. Addition of sodium salt suppresses bitterness of 2A to gLMS 9, and 2B to gLMS 4. We investigated whether the observed bitterness suppression of the mixture A + B (Equation 1) can be predicted from bitterness suppression of its components single concentration (A and B, Equations 2 and 3) or double concentration (2A and 2B, Equations 5 and 6). The predictions based upon summing Equations 2 and 3 and averaging Equations 5 and 6 are found to the right. Trapezoids represent the medicine cup from which the solutions were sampled, and the numbers inside represent the bitterness ratings. one side of the tongue and a Na+ salt to the other side of the tongue (split-tongue methodology). The stimuli were applied independently and simultaneously. The intensity of bitterness was reduced more when the stimuli were applied to the tongue in mixture together, compared to independent simultaneous application of the two stimuli on different sides of the tongue. This conclusion is possible because the two lateral halves of the tongue are neurologically independent until the asc (...truncated)