Investigation of synergism in binary mixtures of sweeteners

Schiffman, Susan S.; Booth, B; Carr, B. Thomas; Losee, Michael L.; Sattely‐Miller, Elizabeth A.; Graham, Brevick G.

doi:10.1016/0361-9230(95)00062-j

Cited by 101 publications

(77 citation statements)

References 22 publications

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“…Up to now, sweetness enhancement has been reported only for sweetener combinations apparently showing modest synergistic effects in taste tests (25,26). However, results from studies measuring the effect of sweetener combinations are difficult to interpret because of the inherent sweetness of each of the mixture components and their different psychophysical functions (their relative sweetness intensity at increasing concentrations) (27).…”

Section: Resultsmentioning

confidence: 99%

Positive allosteric modulators of the human sweet taste receptor enhance sweet taste

Servant¹,

Tachdjian²,

Tang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

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To identify molecules that could enhance sweetness perception, we undertook the screening of a compound library using a cellbased assay for the human sweet taste receptor and a panel of selected sweeteners. In one of these screens we found a hit, SE-1, which significantly enhanced the activity of sucralose in the assay. At 50 μM, SE-1 increased the sucralose potency by >20-fold. On the other hand, SE-1 exhibited little or no agonist activity on its own. SE-1 effects were strikingly selective for sucralose. Other popular sweeteners such as aspartame, cyclamate, and saccharin were not enhanced by SE-1 whereas sucrose and neotame potency were increased only by 1.3-to 2.5-fold at 50 μM. Further assayguided chemical optimization of the initial hit SE-1 led to the discovery of SE-2 and SE-3, selective enhancers of sucralose and sucrose, respectively. SE-2 (50 μM) and SE-3 (200 μM) increased sucralose and sucrose potencies in the assay by 24-and 4.7-fold, respectively. In human taste tests, 100 μM of SE-1 and SE-2 allowed for a reduction of 50% to >80% in the concentration of sucralose, respectively, while maintaining the sweetness intensity, and 100 μM SE-3 allowed for a reduction of 33% in the concentration of sucrose while maintaining the sweetness intensity. These enhancers did not exhibit any sweetness when tasted on their own. Positive allosteric modulators of the human sweet taste receptor could help reduce the caloric content in food and beverages while maintaining the desired taste.enhancer | sweetness | perception | sucrose T he steady increase of the daily consumption of dietary sugar over the last decades may have contributed to the obesity crisis and the early onset of type-II diabetes observed in many developed countries (1, 2). As a result, food and beverage companies have launched a plethora of diet brands where sugar has been partly or fully replaced by noncaloric sweeteners to decrease caloric intake. Currently some of the commonly used noncaloric sweeteners include saccharin, aspartame, cyclamate, sucralose, and acesulfame K (3, 4). However, none of these substances can completely reproduce the taste of sugar. These sweeteners all suffer from one or more shortcomings including a bitter or metallic aftertaste at high concentrations, limiting their use to lower concentrations, or temporal issues such as a delayed sweet taste onset, a lingering sweet aftertaste, or a limited maximum sweetness intensity (4, 5). Another appealing approach to address the problem, in addition to looking for novel noncaloric sweeteners, would be to find molecules capable of enhancing sweetness perception. Ideally, such an enhancer molecule would not elicit sweetness on its own but it would boost the sweetness intensity of a lower amount of sweetener or sugar. Such enhancers could therefore allow for a reduction in the amount of sugar, and calories, in food and beverages while maintaining the desired taste. Similarly, a sweet taste enhancer could allow for a reduction in the amount of noncaloric sweeteners used in "0"-calorie...

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Section: Resultsmentioning

confidence: 99%

Positive allosteric modulators of the human sweet taste receptor enhance sweet taste

Servant¹,

Tachdjian²,

Tang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

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“…However, there are some indications that oral sweet taste processing is also more complex and may include a synergistic mechanism, much like the one proposed here to underlie sweet taste detection in the GI tract. Adding glucose to an artificial sweet taste solution applied to the oral receptors results in a more robust signal than would be expected from a simple additive effect (16,38,44). This Saccϩglucose synergy is thought to happen as a result of the two ligands simultaneously binding at distinct loci on the oral T1R2ϩT1R3 complex, though this mechanism has been purely speculative to date (38).…”

Section: Discussionmentioning

confidence: 99%

Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise

Schier

Davidson

Powley

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Schier LA, Davidson TL, Powley TL. Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise. Am J Physiol Regul Integr Comp Physiol 302: R1351-R1363, 2012. First published March 14, 2012 doi:10.1152/ajpregu.00702.2011.-In a previous report (Schier et al., Am J Physiol Regul Integr Comp Physiol 301: R1557-R1568, 2011, we demonstrated with a new behavioral procedure that rats exhibit stimulus-bound suppression of intake in response to an intraduodenal (ID) bitter tastant predicting subsequent malaise. With the use of the same modified taste aversion procedure, the present experiments evaluated whether the sweet taste properties of ID stimuli are likewise detected and encoded. Thirsty rats licked at sipper spouts for hypotonic NaCl for 30 min and received brief (first 6 min) yoked ID infusions of either the same NaCl or an isomolar lithium chloride (LiCl) solution in each session. An intestinal taste cue was mixed directly into the LiCl infusate for aversion training. Results showed that rats failed to detect intestinal sweet taste alone (20 mM Sucralose) but clearly suppressed licking in response to a nutritive sweet taste stimulus (234 mM sucrose) in the intestine that had been repeatedly paired with LiCl. Rats trained with ID sucrose in LiCl subsequently generalized responding to ID Sucralose alone at test. Replicating this, rats trained with ID Sucralose in compound with 80 mM Polycose rapidly suppressed licking to the 20 mM Sucralose alone in a later test. Furthermore, ID sweet taste signaling did not support the rapid negative feedback of sucrose or Polycose on intake when their digestion and transport were blocked. Together, these results suggest that other signaling pathways and/or transporters engaged by caloric carbohydrate stimuli potentiate detection of sweet taste signals in the intestine.gastrointestinal; taste receptor; preabsorptive signals; artificial sweetener; food learning THE DISCOVERIES that putative chemoreceptive cells in the epithelium of the gastrointestinal (GI) tract express taste receptor molecules and intracellular signaling proteins (e.g., 3, 4, 10, 17-19, 22, 27, 28, 48, 53) as well as exhibit morphological features resembling those of taste cells on the tongue (e.g., 12, 18) have stimulated interest in how preabsorptive food-related signals arising from the lumen of the GI tract are transduced to affect digestion and ingestion (see, for example, the series of review articles entitled "Nutrient Tasting and Signaling Mechanisms in the Gut" published in American Journal of Physiology: Refs. 5,13,20,32,41). To address such questions, we recently developed and employed a new behavioral paradigm to demonstrate that a bitter tastant in the duodenum produces stimulus-bound reductions in ongoing ingestion (37). The present set of experiments addresses similar functional questions using the same behavioral paradigm to evaluate the effects of sweet tastants in the duodenum.

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“…For instance, sodium ions and some sweeteners can suppress the bitterness of various compounds in binary mixtures (Lawless, 1979;Kroeze and Bartoshuk, 1985;Schiffman et al, 1985;Calviño et al, 1990;Calviño and Garrido, 1991;Schifferstein and Frijters, 1993;Frijters and Schifferstein, 1994;Schiffman et al, 1994;Beauchamp, 1995, 1997;Stevens, 1995;Prescott et al, 2001). Moreover, synergistic interactions occur between some sweeteners (Kamen, 1959;Stone and Oliver, 1969;Bartoshuk and Cleveland, 1977;Frank et al, 1989;Ayya and Lawless, 1992;Schifferstein, 1995Schifferstein, , 1996Schiffman et al, 1995). Conversely, it is unclear whether the perceived bitterness of binary bitter-compound mixtures is, in general, merely an additive function of the total bitter-inducing chemicals in the mouth, suggesting a lack of mutual interactions among bitter substances or, alternatively, whether bitter-compound mixtures exert suppression and/or synergistic effects.…”

Section: Introductionmentioning

confidence: 99%

Receptor Agonism and Antagonism of Dietary Bitter Compounds

Brockhoff¹,

Behrens²,

Roudnitzky³

et al. 2011

J. Neurosci.

106

105

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Food contains complex blends of structurally diverse bitter compounds that trigger bitterness through activation of one or more of the ϳ25 human TAS2 bitter taste receptors. It remains unsolved, however, whether the perceived bitterness of binary bitter-compound mixtures can be considered an additive function of all bitter-inducing chemicals in the mouth, suggesting that little mutual interaction takes place among bitter substances or if mixture suppression and synergism occurs. Here we report on two natural sesquiterpene lactones from edible plants, which stimulate distinct sets of hTAS2Rs in transfected cells. Both chemicals also robustly inhibit different but overlapping subsets of agonist-activated hTAS2Rs. These findings demonstrate that mixtures of bitter compounds, because they normally occur in human foodstuff, likely elicit bitter perception in a complex and not in a merely additive manner. An unexpected implication of this discovery is that, during evolution, the naturally occurring bitter taste receptor antagonists have shaped some of the pharmacological properties of the receptors, such as overlapping recognition profiles and breadth of tuning.

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Investigation of synergism in binary mixtures of sweeteners

Cited by 101 publications

References 22 publications

Positive allosteric modulators of the human sweet taste receptor enhance sweet taste

Positive allosteric modulators of the human sweet taste receptor enhance sweet taste

Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise

Receptor Agonism and Antagonism of Dietary Bitter Compounds

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