Rebaudioside A and Rebaudioside D Bitterness do not Covary with Acesulfame-K Bitterness or Polymorphisms in TAS2R9 and TAS2R31
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In order to reduce calories in foods and beverages, the food industry routinely uses non-nutritive sweeteners. Unfortunately, many are synthetically derived, and many consumers have a strong preference for natural sweeteners, irrespective of the safety data on synthetic non-nutritive sweeteners. Additionally, many non-nutritive sweeteners elicit aversive side tastes, such as bitter and metallic, in addition to sweetness. Bitterness thresholds of acesulfame-K (AceK) and saccharin are known to vary across bitter taste receptor polymorphisms in TAS2R31. Rebaudioside A (RebA) has been shown to activate hTAS2R4 and hTAS2R14 in vitro. Here, we examined the bitterness and sweetness perception of natural and synthetic non-nutritive sweeteners. In a follow-up to a previous gene association study, participants (n = 122) who had been genotyped previously rated sweet, bitter, and metallic sensations from RebA, rebaudioside D (RebD), aspartame, sucrose, and gentiobiose in duplicate in a single session. For comparison, we also present sweet and bitter ratings of AceK collected in the original experiment for the same participants. At similar sweetness levels, aspartame elicited less bitterness than RebD, which was significantly less bitter than RebA. The bitterness of RebA and RebD showed wide variability across individuals, and bitterness ratings for these compounds were correlated. However, RebA and RebD bitterness did not covary with AceK bitterness. Likewise, single-nucleotide polymorphisms (SNPs) shown previously to explain the variation in the suprathreshold bitterness of AceK (rs3741845 in TAS2R9 and rs10772423 in TAS2R31) did not explain the variation in RebA and RebD bitterness. Because RebA activates hT2R4 and hT2R14, an SNP in TAS2R4 previously associated with variation in bitterness perception was included here; there are no known functional SNPs for TAS2R14. In the present data, a putatively functional SNP (rs2234001) in TAS2R4 did not explain the variation in RebA or RebD bitterness. Collectively, these data indicate that the bitterness of RebA and RebD cannot be predicted by AceK bitterness, reinforcing our view that bitterness is not a simple monolithic trait that is high or low in an individual. This also implies that consumers who reject AceK may not find RebA and RebD aversive, and vice versa. Finally, RebD may be a superior natural non-nutritive sweetener to RebA, as it elicits significantly less bitterness at similar levels of sweetness.
KeywordsBitterness Non-nutritive sweetener Rebaudioside A Rebaudioside D Genetics Taste phenotype Project GIANT-CS
This manuscript was completed in partial fulfillment of the requirements for a Master of Science degree at the Pennsylvania State University by the first author. The authors would like to thank Dr. Emma L. Feeney, Nadia K. Byrnes, Meghan Kane, and Rachel J. Primrose for collecting the psychophysical data and leading the training sessions, Samantha M. Bennett for the assistance with protocol development, and Kayla Beaucage for genotyping our DNA samples. We also thank our study participants for their time and participation. This work was partially supported by a National Institutes of Health grant from the National Institute National of Deafness and Communication Disorders [DC010904] to the corresponding author, United States Department of Agriculture Hatch Project PEN04332 funds, funds from the Pennsylvania State University, and a VA shared equipment grant to JEM.
Compliance with Ethics Requirements
Conflict of Interest
Alissa L. Allen declares that she has no conflict of interest.
John E. McGeary declares that he has no conflict of interest.
John E. Hayes has received speaking fees from Tate & Lyle PLC, Symrise AG, and General Mills, Inc. for unrelated projects. He also serves on the Scientific Advisory Board of Medifast, Inc. None of these organizations have had any influence over study design or interpretation, or the decision to publish these results.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.
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