Advertisement

The Behavior Analyst

, Volume 38, Issue 1, pp 1–17 | Cite as

Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners

  • Susan E. Swithers
Article

Abstract

While no single factor accounts for the significant increases in overweight and obesity that have emerged during the past several decades, evidence now suggests that sugars, in general, and sugar-sweetened beverages, in particular, may be especially problematic. One response to this concern has been an explosion in the availability and use of noncaloric sweeteners as replacements for sugar. While consumers have been led to believe that such substitutes are healthy, long-term epidemiological data in a number of cohorts have documented increased risk for negative outcomes like type 2 diabetes, heart disease, and stroke among users of artificial sweeteners. Experimental data from animals has provided several plausible mechanisms that could explain this counterintuitive relationship. In particular, my research has demonstrated that artificial sweeteners appear to interfere with basic learned, predictive relations between sweet tastes and post-ingestive consequences such as the delivery of energy. By interfering with these relations, artificial sweeteners inhibit anticipatory responses that normally serve to maintain physiological homeostasis, and over the long term, this interference could result in negative health effects like those seen in the human cohort studies. These data suggest that reducing the consumption of all sweeteners is advisable to promote better health.

Keywords

Artificial sweeteners Health Obesity Classical conditioning 

Notes

Acknowledgments

Thanks to Peter Urcuioli for his helpful comments on a previous version of this manuscript.

Conflict of Interest

The author declares that she has no conflicts of interest.

Compliance with Ethical Standards

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of, and were approved by, the Purdue University Animal Care and Use Committee. This article does not contain any studies with human participants performed by the author. This work was funded by Purdue University and NIH grants R01DK55531 and P01HD052112.

References

  1. Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health, Part A, 71(21), 1415–1429. doi: 10.1080/15287390802328630.CrossRefGoogle Scholar
  2. Bernstein, A. M., de Koning, L., Flint, A. J., Rexrode, K. M., & Willett, W. C. (2012). Soda consumption and the risk of stroke in men and women. The American Journal of Clinical Nutrition, 95(5), 1190–1199. doi: 10.3945/ajcn.111.030205.CrossRefPubMedCentralPubMedGoogle Scholar
  3. Bhupathiraju, S. N., Pan, A., Malik, V. S., Manson, J. E., Willett, W. C., van Dam, R. M., & Hu, F. B. (2013). Caffeinated and caffeine-free beverages and risk of type 2 diabetes. The American Journal of Clinical Nutrition, 97(1), 155–166. doi: 10.3945/ajcn.112.048603.CrossRefPubMedGoogle Scholar
  4. Bills, C. H., Dopheide, M., Pineno, O., & Schachtman, T. R. (2006). Effects of an extinguished CS on competition with another CS. Behavioural Processes, 72(1), 14–22. doi: 10.1016/j.beproc.2005.11.009.CrossRefPubMedGoogle Scholar
  5. Calorie Control Council. (2014). Trends and statistics. Retrieved November 19, 2014, 2014, from (http://www.caloriecontrol.org/press-room/trends-and-statistics).
  6. Calton, J. L., Mitchell, K. G., & Schachtman, T. R. (1996). Conditioned inhibition produced by extinction of a conditioned stimulus. Learning and Motivation, 27(4), 335–361.CrossRefPubMedGoogle Scholar
  7. Centers for Disease Control and Prevention (2014). Leading causes of death. Retrieved December 10, 2014, 2014, from http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
  8. Chandon, P. (2012). How package design and packaged-based marketing claims lead to overeating. Applied Economic Perspectives and Policy. doi: 10.1093/aepp/pp s028.Google Scholar
  9. Cohen, L., Curhan, G., & Forman, J. (2012). Association of sweetened beverage intake with incident hypertension. Journal of General Internal Medicine, 27(9), 1127–1134. doi: 10.1007/s11606-012-2069-6.CrossRefPubMedCentralPubMedGoogle Scholar
  10. Davidson, T. L., & Swithers, S. E. (2004). A Pavlovian approach to the problem of obesity. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 28(7), 933–935. doi: 10.1038/sj.ijo.0802660.CrossRefGoogle Scholar
  11. Davidson, T. L., Martin, A. A., Clark, K., & Swithers, S. E. (2011). Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation. Quarterly Journal of Experimental Psychology (Hove), 64(7), 1430–1441. doi: 10.1080/17470218.2011.552729.CrossRefGoogle Scholar
  12. de Koning, L., Malik, V. S., Rimm, E. B., Willett, W. C., & Hu, F. B. (2011). Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. The American Journal of Clinical Nutrition, 93(6), 1321–1327. doi: 10.3945/ajcn.110.007922.CrossRefPubMedCentralPubMedGoogle Scholar
  13. De Koning, L., Malik, V. S., Kellogg, M. D., Rimm, E. B., Willett, W. C., & Hu, F. B. (2012). Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men. Circulation, 125(14), 1735–1741. doi: 10.1161/circulationaha.111.067017. S1731.CrossRefPubMedCentralPubMedGoogle Scholar
  14. Dhingra, R., Sullivan, L., Jacques, P. F., Wang, T. J., Fox, C. S., Meigs, J. B., & Vasan, R. S. (2007). Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation, 116(5), 480–488. doi: 10.1161/CIRCULATIONAHA.107.689935.CrossRefPubMedGoogle Scholar
  15. Duffey, K. J., Steffen, L. M., Van Horn, L., Jacobs, D. R., Jr., & Popkin, B. M. (2012). Dietary patterns matter: diet beverages and cardiometabolic risks in the longitudinal coronary artery risk development in young adults (CARDIA) study. The American Journal of Clinical Nutrition, 95(4), 909–915. doi: 10.3945/ajcn.111.026682.CrossRefPubMedCentralPubMedGoogle Scholar
  16. Fagherazzi, G., Vilier, A., Saes Sartorelli, D., Lajous, M., Balkau, B., & Clavel-Chapelon, F. (2013). Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the etude epidemiologique aupres des femmes de la mutuelle generale de l’Education nationale-european prospective investigation into cancer and nutrition cohort. The American Journal of Clinical Nutrition, 97(3), 517–523. doi: 10.3945/ajcn.112.050997.CrossRefPubMedGoogle Scholar
  17. Fitch, C., & Keim, K. S. (2012). Position of the academy of nutrition and dietetics: use of nutritive and nonnutritive sweeteners. Journal of the Academy of Nutrition and Dietetics, 112(5), 739–758. doi: 10.1016/j.jand.2012.03.009.CrossRefPubMedGoogle Scholar
  18. Flegal, K. M., Carroll, M. D., Kit, B. K., & Ogden, C. L. (2012). Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. Journal of the American Medical Association, 307(5), 491–497. doi: 10.1001/jama.2012.39.CrossRefPubMedGoogle Scholar
  19. Fung, T. T., Malik, V., Rexrode, K. M., Manson, J. E., Willett, W. C., & Hu, F. B. (2009). Sweetened beverage consumption and risk of coronary heart disease in women. The American Journal of Clinical Nutrition, 89(4), 1037–1042. doi: 10.3945/ajcn.2008.27140.CrossRefPubMedCentralPubMedGoogle Scholar
  20. Garcia, J., Kimeldorf, D. J., & Koelling, R. A. (1955). Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science (New York, N.Y.), 122(3160), 157–158.Google Scholar
  21. Gardener, H., Rundek, T., Markert, M., Wright, C. B., Elkind, M. S., & Sacco, R. L. (2012). Diet soft drink consumption is associated with an increased risk of vascular events in the northern Manhattan study. Journal of General Internal Medicine. doi: 10.1007/s11606-011-1968-2.PubMedCentralPubMedGoogle Scholar
  22. Gardner, C., Wylie-Rosett, J., Gidding, S. S., Steffen, L. M., Johnson, R. K., Reader, D., & Lichtenstein, A. H. (2012). Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American heart association and the American diabetes association. Circulation, 126(4), 509–519. doi: 10.1161/CIR.0b013e31825c42ee.CrossRefPubMedGoogle Scholar
  23. Green, E., & Murphy, C. (2012). Altered processing of sweet taste in the brain of diet soda drinkers. Physiology & Behavior, 107(4), 560–567. doi: 10.1016/j.physbeh.2012.05.006.CrossRefGoogle Scholar
  24. Health, A. C. o. S. a. (2007). Health group says new study on soda is grasping at straws. Retrieved 11/24/2014, 2014, from http://acsh.org/2007/07/health-group-says-new-study-on-soda-is-grasping-at-straws/
  25. Hu, F. B. (2013). Resolved: there is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity, 14(8), 606–619. doi: 10.1111/obr.12040.CrossRefGoogle Scholar
  26. LeBlanc, J., & Cabanac, M. (1989). Cephalic postprandial thermogenesis in human subjects. Physiology & Behavior, 46(3), 479–482.CrossRefGoogle Scholar
  27. LeBlanc, J., Cabanac, M., & Samson, P. (1984). Reduced postprandial heat production with gavage as compared with meal feeding in human subjects. The American Journal of Physiology, 246(1 Pt 1), E95–E101.PubMedGoogle Scholar
  28. Livingstone, M. B., & Black, A. E. (2003). Markers of the validity of reported energy intake. The Journal of Nutrition, 133(3), 895S–920S.PubMedGoogle Scholar
  29. Lutsey, P. L., Steffen, L. M., & Stevens, J. (2008). Dietary intake and the development of the metabolic syndrome: the atherosclerosis risk in communities study. Circulation, 117(6), 754–761. doi: 10.1161/CIRCULATIONAHA.107.716159.CrossRefPubMedGoogle Scholar
  30. Mattes, R. D., & Popkin, B. M. (2009). Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. The American Journal of Clinical Nutrition, 89(1), 1–14. doi: 10.3945/ajcn.2008.26792.CrossRefPubMedCentralPubMedGoogle Scholar
  31. McDowell, M. A., Fryar, C. D., Ogden, C. L., & Flegal, K. M. (2008). Anthropometric reference data for children and adults: United States, 2003–2006. National Health Statistics Reports (Vol. 10). Hyattsville, MD: National Center for Health Statistics.Google Scholar
  32. National Center for Health Statistics (2012). Health E-Stats September. Retrieved May 28, 2013, from http://www.cdc.gov/nchs/data/hestat/ obesity_adult_09_10/obesity_adult_09_10.pdf
  33. Nettleton, J. A., Polak, J. F., Tracy, R., Burke, G. L., & Jacobs, D. R., Jr. (2009). Dietary patterns and incident cardiovascular disease in the multi-ethnic study of atherosclerosis. The American Journal of Clinical Nutrition, 90(3), 647–654. doi: 10.3945/ajcn.2009.27597.CrossRefPubMedCentralPubMedGoogle Scholar
  34. Ng, S. W., Slining, M. M., & Popkin, B. M. (2012). Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005–2009. Journal of the Academy of Nutrition and Dietetics, 112(11), 1828–1834. doi: 10.1016/j.jand.2012.07.009. e1821-1826.CrossRefPubMedCentralPubMedGoogle Scholar
  35. Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., Margono, C., & Gakidou, E. (2014). Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet, 384(9945), 766–781. doi: 10.1016/s0140-6736(14)60460-8.CrossRefPubMedGoogle Scholar
  36. Ogden, C. L., Fryar, C. D., Carroll, M. D., & Flegal, K. M. (2004). Mean body weight, height, and body mass index, United States 1960–2002. Advance Data from Vital and Health Statistics (Vol. 347). Hyattsville, Maryland: National Center for Health Statistics.Google Scholar
  37. Palmnas, M. S., Cowan, T. E., Bomhof, M. R., Su, J., Reimer, R. A., Vogel, H. J., & Shearer, J. (2014). Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS ONE, 9(10), e109841. doi: 10.1371/journal.pone.0109841.CrossRefPubMedCentralPubMedGoogle Scholar
  38. Pavlov, I. P., & Anrep, G. V. E. (1960). Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex; Translated [from the Russian] and edited by GV Anrep: Dover Publications.Google Scholar
  39. Piernas, C., Tate, D. F., Wang, X., & Popkin, B. M. (2013). Does diet-beverage intake affect dietary consumption patterns? results from the choose healthy options consciously everyday (CHOICE) randomized clinical trial. The American Journal of Clinical Nutrition, 97(3), 604–611. doi: 10.3945/ajcn.112.048405.CrossRefPubMedCentralPubMedGoogle Scholar
  40. Romaguera, D., Norat, T., Wark, P. A., Vergnaud, A. C., Schulze, M. B., van Woudenbergh, G. J., . . . Wareham, N. J. (2013). Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct. Diabetologia.Google Scholar
  41. Rudenga, K. J., & Small, D. M. (2012). Amygdala response to sucrose consumption is inversely related to artificial sweetener use. Appetite, 58(2), 504–507. doi: 10.1016/j.appet.2011.12.001.CrossRefPubMedCentralPubMedGoogle Scholar
  42. Sakurai, M., Nakamura, K., Miura, K., Takamura, T., Yoshita, K., Nagasawa, S. Y., & Nakagawa, H. (2013). Sugar-sweetened beverage and diet soda consumption and the 7-year risk for type 2 diabetes mellitus in middle-aged Japanese men. European Journal of Nutrition. doi: 10.1007/s00394-013-0523-9.PubMedGoogle Scholar
  43. Sclafani, A. (1997). Learned controls of ingestive behaviour. Appetite, 29(2), 153–158. doi: 10.1006/appe.1997.0120.CrossRefPubMedGoogle Scholar
  44. Sivertsen, J., Rosenmeier, J., Holst, J. J., & Vilsboll, T. (2012). The effect of glucagon-like peptide 1 on cardiovascular risk. Nature Reviews Cardiology, 9(4), 209–222. doi: 10.1038/nrcardio.2011.211.CrossRefPubMedGoogle Scholar
  45. Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., & Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181–186. doi: 10.1038/nature13793.PubMedGoogle Scholar
  46. Swithers, S. E. (2013). Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends in Endocrinology and Metabolism, 24(9), 431–441. doi: 10.1016/j.tem.2013.05.005.CrossRefPubMedCentralPubMedGoogle Scholar
  47. Swithers, S. E., & Davidson, T. L. (2005). Obesity: outwitting the wisdom of the body? Current Neurology and Neuroscience Reports, 5(3), 159–162.CrossRefPubMedGoogle Scholar
  48. Swithers, S. E., & Davidson, T. L. (2008). A role for sweet taste: calorie predictive relations in energy regulation by rats. Behavioral Neuroscience, 122(1), 161–173. doi: 10.1037/0735-7044.122.1.161.CrossRefPubMedGoogle Scholar
  49. Swithers, S. E., Doerflinger, A., & Davidson, T. L. (2006). Consistent relationships between sensory properties of savory snack foods and calories influence food intake in rats. International Journal of Obesity (2005), 30(11), 1685–1692. doi: 10.1038/sj.ijo.0803329.CrossRefGoogle Scholar
  50. Swithers, S. E., Baker, C. R., & Davidson, T. L. (2009). General and persistent effects of high-intensity sweeteners on body weight gain and caloric compensation in rats. Behavioral Neuroscience, 123(4), 772–780. doi: 10.1037/a0016139.CrossRefPubMedCentralPubMedGoogle Scholar
  51. Swithers, S. E., Martin, A. A., Clark, K. M., Laboy, A. F., & Davidson, T. L. (2010a). Body weight gain in rats consuming sweetened liquids. Effects of caffeine and diet composition. Appetite, 55(3), 528–533. doi: 10.1016/j.appet.2010.08.021.CrossRefPubMedCentralPubMedGoogle Scholar
  52. Swithers, S. E., Martin, A. A., & Davidson, T. L. (2010b). High-intensity sweeteners and energy balance. Physiology & Behavior, 100(1), 55–62. doi: 10.1016/j.physbeh.2009.12.021.CrossRefGoogle Scholar
  53. Swithers, S. E., Ogden, S. B., & Davidson, T. L. (2011). Fat substitutes promote weight gain in rats consuming high-fat diets. Behavioral Neuroscience, 125(4), 512–518. doi: 10.1037/a0024404.CrossRefPubMedCentralPubMedGoogle Scholar
  54. Swithers, S. E., Laboy, A. F., Clark, K., Cooper, S., & Davidson, T. L. (2012a). Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats. Behavioural Brain Research, 233(1), 1–14. doi: 10.1016/j.bbr.2012.04.024.CrossRefPubMedCentralPubMedGoogle Scholar
  55. Swithers, S. E., Ogden, S. B., Laboy, A. F., & Davidson, T. L. (2012b). Saccharin pre-exposure enhances appetitive flavor learning in pre-weanling rats. Developmental Psychobiology, 54(8), 818–824. doi: 10.1002/dev.21047.CrossRefPubMedCentralPubMedGoogle Scholar
  56. Swithers, S. E., Sample, C. H., & Davidson, T. L. (2013a). Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats. Behavioral Neuroscience, 127(2), 262–274. doi: 10.1037/a0031717.CrossRefPubMedCentralPubMedGoogle Scholar
  57. Swithers, S. E., Sample, C. H., & Katz, D. P. (2013b). Influence of ovarian and non-ovarian estrogens on weight gain in response to disruption of sweet taste—calorie relations in female rats. Hormones and Behavior, 63(1), 40–48. doi: 10.1016/j.yhbeh.2012.11.003.CrossRefPubMedCentralPubMedGoogle Scholar
  58. Sylvetsky, A. C., Welsh, J. A., Brown, R. J., & Vos, M. B. (2012). Low-calorie sweetener consumption is increasing in the United States. The American Journal of Clinical Nutrition, 96(3), 640–646. doi: 10.3945/ajcn.112.034751.CrossRefPubMedCentralPubMedGoogle Scholar
  59. Sylvetsky, A. C., Greenberg, M., Zhao, X., & Rother, K. I. (2014). What parents think about giving nonnutritive sweeteners to their children: a pilot study. International Journal of Pediatrics, 2014, 819872. doi: 10.1155/2014/819872.CrossRefPubMedCentralPubMedGoogle Scholar
  60. Teff, K. L. (2011). How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiology & Behavior, 103(1), 44–50. doi: 10.1016/j.physbeh.2011.01.012.CrossRefGoogle Scholar
  61. USDA Economic Research Service. (2008). Beverages: per capita consumption. Retrieved October 26, 2008, from http://www.ers.usda.gov/data/foodconsumption/spreadsheets/beverage.xls.
  62. Yang, Q. (2010). Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. The Yale Journal of Biology and Medicine, 83(2), 101–108.PubMedCentralPubMedGoogle Scholar
  63. Young, L. R., & Nestle, M. (2002). The contribution of expanding portion sizes to the US obesity epidemic. American Journal of Public Health, 92(2), 246–249.CrossRefPubMedCentralPubMedGoogle Scholar
  64. Young, L. R., & Nestle, M. (2007). Portion sizes and obesity: responses of fast-food companies. Journal of Public Health Policy, 28(2), 238–248. doi: 10.1057/palgrave.jphp.3200127.CrossRefPubMedGoogle Scholar

Copyright information

© Association for Behavior Analysis International 2015

Authors and Affiliations

  1. 1.Department of Psychological SciencesPurdue UniversityWest LafayetteUSA

Personalised recommendations