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

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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.

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References

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Calorie Control Council. (2014). Trends and statistics. Retrieved November 19, 2014, 2014, from (http://www.caloriecontrol.org/press-room/trends-and-statistics).

  • 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.

    Article  PubMed  Google Scholar 

  • 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

  • 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 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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/

  • 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.

    Article  Google Scholar 

  • LeBlanc, J., & Cabanac, M. (1989). Cephalic postprandial thermogenesis in human subjects. Physiology & Behavior, 46(3), 479–482.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Livingstone, M. B., & Black, A. E. (2003). Markers of the validity of reported energy intake. The Journal of Nutrition, 133(3), 895S–920S.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

  • 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

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Sclafani, A. (1997). Learned controls of ingestive behaviour. Appetite, 29(2), 153–158. doi:10.1006/appe.1997.0120.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • Swithers, S. E., & Davidson, T. L. (2005). Obesity: outwitting the wisdom of the body? Current Neurology and Neuroscience Reports, 5(3), 159–162.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • USDA Economic Research Service. (2008). Beverages: per capita consumption. Retrieved October 26, 2008, from http://www.ers.usda.gov/data/foodconsumption/spreadsheets/beverage.xls.

  • 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.

    PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

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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.

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Swithers, S.E. Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners. BEHAV ANALYST 38, 1–17 (2015). https://doi.org/10.1007/s40614-015-0028-3

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