Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners
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.
KeywordsArtificial sweeteners Health Obesity Classical conditioning
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.
- 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
- Calorie Control Council. (2014). Trends and statistics. Retrieved November 19, 2014, 2014, from (http://www.caloriecontrol.org/press-room/trends-and-statistics).
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.PubMedCentralPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.Google Scholar
- 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.CrossRefPubMedCentralPubMedGoogle 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.CrossRefPubMedGoogle 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.Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- USDA Economic Research Service. (2008). Beverages: per capita consumption. Retrieved October 26, 2008, from http://www.ers.usda.gov/data/foodconsumption/spreadsheets/beverage.xls.