Variation in the TAS2R31 bitter taste receptor gene relates to liking for the nonnutritive sweetener Acesulfame-K among children and adults

Nuala Bobowski, Danielle R Reed, Julie A Mennella, Nuala Bobowski, Danielle R Reed, Julie A Mennella

Abstract

The nonnutritive sweetener (NNS) acesulfame potassium (Ace-K) elicits a bitter off-taste that varies among adults due to polymorphisms in a bitter taste receptor gene. Whether polymorphisms affect liking for Ace-K by children, who live in different sensory worlds, is unknown. We examined hedonic response to Ace-K among children compared to adults, and whether response was related to common variants of the TAS2R31 bitter taste receptor gene and to NNS intake. Children (N = 48) and their mothers (N = 34) rated liking of Ace-K, and mothers reported whether they or their children ever consume NNSs via questionnaire. Participants were genotyped for TAS2R31 variant sites associated with adult perception of Ace-K (R35W, L162M, A227V, and V240I). Regardless of age, more participants with 1 or no copies than with 2 copies of the TAS2R31 WMVI haplotype liked Ace-K (p = 0.01). NNS-sweetened products were consumed by 50% and 15% of mothers and children, respectively, with no association between intake and TAS2R31. The TAS2R31 WMVI haplotype was partly responsible for children's hedonic response to Ace-K, highlighting a potential role for inborn differences in vulnerability to overconsumption of Ace-K-containing products. Currently available methods to measure NNS intake yield crude estimates at best, suggesting self-reports are not reflective of actual intake.

Figures

Figure 1. Relation between number of TAS2R31…
Figure 1. Relation between number of TAS2R31 WMVI alleles and hedonics of Ace-K.
More participants with 2 (n = 9) alleles indicated 0.012 M Ace-K had a bad taste on the 3-point facial hedonic scale than did those with 1 (n = 41) or no (n = 17) alleles (Yates’s χ2 = 12.2, p < 0.01).
Figure 2. Relation between TAS2R38 genotype and…
Figure 2. Relation between TAS2R38 genotype and hedonics of PROP.
More participants with the bitter-sensitive PP genotype (n = 17) indicated 56 μM PROP had a bad taste on the 3-point facial hedonic scale than did AP (n = 31) or AA (n = 19) participants (Yates’s χ2 = 8.5, p < 0.01).
Figure 3. Variants of the bitter receptor…
Figure 3. Variants of the bitter receptor genes TAS2R31 and TAS2R38.
Boxes denote variant sites, e.g., TAS2R31 R35W indicates the location in the peptide (position 35) where arginine (R) is replaced by tryptophan (W). Non- or less functional genotypes are in blue whereas functional genotypes are in red.

References

    1. Mennella J. A. & Bobowski N. K. The sweetness and bitterness of childhood: insights from basic research on taste preferences. Physiol Behav 152, 502–507 (2015).
    1. Popkin B. M. & Nielsen S. J. The sweetening of the world’s diet. Obes Res 11, 1325–1332 (2003).
    1. Ng S. W., Slining M. M. & Popkin B. M. Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005–2009. J Acad Nutr Diet 112, 1828–1834, e1821–1826 (2012).
    1. Birch L. L. & Anzman-Frasca S. Learning to prefer the familiar in obesogenic environments. Nestle Nutr Workshop Ser Pediatr Program 68, 187–196, discussion 196–189 (2011).
    1. Mennella J. A., Bobowski N. K. & Reed D. R. The development of sweet taste: from biology to hedonics. Rev Endocr Metab Disord, doi: 10.1007/s11154-016-9360-5 (2016).
    1. Johnson R. K. et al.. Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation 120, 1011–1020 (2009).
    1. Welsh J. A., Sharma A., Cunningham S. A. & Vos M. B. Consumption of added sugars and indicators of cardiovascular disease risk among US adolescents. Circulation 123, 249–257 (2011).
    1. Welsh J. A. & Cunningham S. A. The role of added sugars in pediatric obesity. Pediatr Clin North Am 58, 1455–1466 (2011).
    1. World Health Organization. Sugars intake for adults and children. World Health Organization (Date of access: 10/31/16) (2015).
    1. Welsh J. A., Sharma A. J., Grellinger L. & Vos M. B. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr 94, 726–734 (2011).
    1. Coldwell S. E. et al.. Gustation assessment using the NIH Toolbox. Neurology 80, S20–24 (2013).
    1. Mennella J. A., Lukasewycz L. D., Griffith J. W. & Beauchamp G. K. Evaluation of the Monell forced-choice, paired-comparison tracking procedure for determining sweet taste preferences across the lifespan. Chem Senses 36, 345–355 (2011).
    1. Drewnowski A. & Rehm C. D. Consumption of added sugars among US children and adults by food purchase location and food source. Am J Clin Nutr 100, 901–907 (2014).
    1. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans 2015–2020: Eighth Edition. Health. gov (Date of access: 10/31/16) (2015).
    1. Nickelson J., Lawrence J. C., Parton J. M., Knowlden A. P. & McDermott R. J. What proportion of preschool-aged children consume sweetened beverages? J Sch Health 84, 185–194 (2014).
    1. Sylvetsky A. C. & Rother K. I. Trends in the consumption of low-calorie sweeteners. Physiol Behav, doi: 10.1016/j.physbeh.2016.03.030 (2016).
    1. Harris J. L. et al.. Cereal FACTS: Evaluating the nutrition quality and marketing of children’s cereals. Cereal F.A.C.T.S. (Food Advertisting to Children and Teens Score) (Date of access: 10/31/16) (2016).
    1. Fooducate. Kool-Aid Soft Drink Mix, Low Calorie, Sugar Free, Cherry. Fooducate (Date of access: 10/31/16) (2016).
    1. Fooducate. Pillsbury Toaster Strudel, Chocolate and Strawberry. Fooducate (Date of access: 10/31/16) (2016).
    1. Yang Q. Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings. Yale J Biol Med 83, 101–108 (2010).
    1. American Dietetic Association. Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. J Am Diet Assoc 104, 255–275 (2004).
    1. Schiffman S. S., Reilly D. A. & Clark T. B. Qualitative differences among sweeteners. Physiol Behav 23, 1–9 (1979).
    1. Schiffman S. S., Booth B. J., Losee M. L., Pecore S. D. & Warwick Z. S. Bitterness of sweeteners as a function of concentration. Brain Res Bull 36, 505–513 (1995).
    1. Allen A. L., McGeary J. E., Knopik V. S. & Hayes J. E. Bitterness of the non-nutritive sweetener acesulfame potassium varies with polymorphisms in TAS2R9 and TAS2R31. Chem Senses 38, 379–389 (2013).
    1. Roudnitzky N. et al.. Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners. Hum Mol Genet 20, 3437–3449 (2011).
    1. Pronin A. N., Hong X., Huixian T., Zhang L., Li Q. & Li X. Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Curr Biol 17, 1403–1408 (2007).
    1. Kuhn C. et al.. Bitter taste receptors for saccharin and acesulfame K. J Neurosci 24, 10260–10265 (2004).
    1. Mennella J. A., Pepino M. Y. & Reed D. R. Genetic and environmental determinants of bitter perception and sweet preferences. Pediatrics 115, e216–222 (2005).
    1. Mennella J. A., Pepino M. Y., Duke F. F. & Reed D. R. Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38. BMC Genet 11, 60 (2010).
    1. Mennella J. A., Pepino M. Y., Duke F. F. & Reed D. R. Psychophysical dissection of genotype effects on human bitter perception. Chem Senses 36, 161–167 (2011).
    1. Mennella J. A. Ontogeny of taste preferences: basic biology and implications for health. Am J Clin Nutr 99, 704S–711S (2014).
    1. Chambers E. Commentary: conducting sensory research in children. J Sens Stud 20, 90–92 (2005).
    1. Mennella J. A. & Beauchamp G. K. Optimizing oral medications for children. Clin Ther 30, 2120–2132 (2008).
    1. Mennella J. A., Pepino M. Y., Lehmann-Castor S. M. & Yourshaw L. M. Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression. Addiction 105, 666–675 (2010).
    1. Mennella J. A., Finkbeiner S. & Reed D. R. The proof is in the pudding: children prefer lower fat but higher sugar than do mothers. Int J Obes (Lond) 36, 1285–1291 (2012).
    1. Beauchamp G. K. & Cowart B. J. Preference for high salt concentrations among children. Dev Psychol 26, 539–545 (1990).
    1. Mennella J. A., Finkbeiner S., Lipchock S. V., Hwang L. D. & Reed D. R. Preferences for salty and sweet tastes are elevated and related to each other during childhood. PLoS One 9, e92201 (2014).
    1. Pepino M. Y. & Mennella J. A. Factors contributing to individual differences in sucrose preference. Chem Senses 30, i319–320 (2005).
    1. Pepino M. Y. & Mennella J. A. Effects of cigarette smoking and family history of alcoholism on sweet taste perception and food cravings in women. Alcohol Clin Exp Res 31, 1891–1899 (2007).
    1. Popper R. & Kroll J. J. Conducting sensory research with children. J Sens Stud 20, 75–87 (2005).
    1. Birch L. L. & Sullivan S. A. Measuring children’s food preferences. J Sch Health 61, 212–214 (1991).
    1. Chen A. W. & Resurreccion A. V. Age appropriate hedonic scales to measure food preferences of young children. J Sens Stud 11, 141–163 (1996).
    1. Bufe B. et al.. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol 15, 322–327 (2005).
    1. Pew Charitable Trust. Philadelphia: the state of the city, a 2016 update. The PEW Charitable Trusts (Date of access: 10/31/16) (2016).
    1. Sylvetsky A. C., Welsh J. A., Brown R. J. & Vos M. B. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr 96, 640–646 (2012).
    1. Piernas C., Ng S. W. & Popkin B. Trends in purchases and intake of foods and beverages containing caloric and low-calorie sweeteners over the last decade in the United States. Pediatr Obes 8, 294–306 (2013).
    1. Sylvetsky A. C., Greenberg M., Zhao X. & Rother K. I. What parents think about giving nonnutritive sweteners to their children: a pilot study. Int J Pediatr 819872, doi: 10.1155/2014/819872 (2014).
    1. Sylvetsky A. C. et al.. Nonnutritive sweeteners in breast milk. J Toxicol Environ Health A 78, 1029–1032 (2015).
    1. Rother K. I., Sylvetsky A. C. & Schiffman S. S. Non-nutritive sweeteners in breast milk: perspective on potential implications of recent findings. Arch Toxicol 89, 2169–2171 (2015).
    1. Brown R. J., de Banate M. A. & Rother K. I. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes 5, 305–312 (2010).
    1. Swithers S. E. Artificial sweeteners are not the answer to childhood obesity. Appetite 93, 85–90 (2015).
    1. Olivier B. et al.. Review of the nutritional benefits and risks related to intense sweeteners. Arch Public Health 73, doi: 10.1186/s13690-015-0092-x (2015).
    1. Piernas C., Ng S. W., Mendez M. A., Gordon-Larsen P. & Popkin B. M. A dynamic panel model of the associations of sweetened beverage purchases with dietary quality and food-purchasing patterns. Am J Epidemiol 181, 661–671 (2015).
    1. Suez J. et al.. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (2014).
    1. Mattes R. D. & Popkin B. M. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 89, 1–14 (2009).
    1. Egan J. M. & Margolskee R. F. Taste cells of the gut and gastrointestinal chemosensation. Mol Interv 8, 78–81 (2008).
    1. Food and Drug Administration. Changes to the Nutrition Facts Label. US Food and Drug Administration (Date of access: 10/31/16) (2016).
    1. Shankar D. Can Food Labels Kill Added Sugar? Bloomberg (Date of access: 10/31/16) (2016).
    1. Hartman L. Non-Nutritive Sweeteners See Increased Potential With New Labels. Food Processing (Date of access: 10/31/16) (2016).
    1. Sylvetsky A. C. & Dietz W. H. Nutrient-content claims-guidance or cause for confusion? NEJM 371, 195–198 (2014).
    1. Azad M. B. et al.. Association between artificially sweetened beverage consumption during pregnancy and infant body mass index. JAMA Pediatr 170, 662–670 (2016).
    1. Wiet S. G. & Beyts P. K. Sensory characteristics of sucralose and other high intensity sweeteners. J Food Sci 57, 1014–1019 (1992).
    1. Siegel S. & Castellan N. J. In Nonparametric statistics for behavioral sciences, 2nd edition (ed. Anker J. D.) 168–189 (McGraw-Hill, 1988).

Source: PubMed

3
Tilaa