YALE JOURNAL OF BIOLOGY AND MEDICINE 83 (2010), pp. 101-108. Copyright © 2010. SYMPOSIUM Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings Neuroscience 2010 Qing Yang Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut America’s obesity epidemic has gathered much media attention recently. A rise in the percent of the population who are obese coincides with an increase in the widespread use of non- caloric artificial sweeteners, such as aspartame (e.g., Diet Coke) and sucralose (e.g., Pepsi One), in food products (Figure 1). Both forward and reverse causalities have been proposed [1,2]. While people often choose “diet” or “light” products to lose weight, research studies suggest that artificial sweeteners may contribute to weight gain. In this mini-review, inspired by a discussion with Dr. Dana Small at Yale’s Neuroscience 2010 conference in April, I first examine the development of artificial sweeteners in a historic context. I then summarize the epidemiological and experimental evidence concerning their effects on weight. Finally, I at- tempt to explain those effects in light of the neurobiology of food reward. HISTORY OF ARTIFICIAL SWEETENERS We owe the discovery of several artifi- cial sweeteners to a few brave scientists who violated the code of laboratory hy- giene and tasted their samples, often inad- vertently [3]. Saccharin, the oldest artificial sweetener, was discovered by Constantine Fahlberg at Johns Hopkins in 1879 [4] while working on coal tar derivatives. For decades after its debut, saccharin remained a specialty product for diabetics on stores’ medicinal shelves [5]. A sugar shortage during World War II and shift of esthetics toward favoring a thin figure encouraged women to turn to artificial substitutes as well [6]. Around this time, the wording on diet soda bottles subtly changed from “for use only in people who must limit sugar in- take” to “for use in people who desire to limit sugar intake” [7]. Saccharin is about To whom all correspondence should be addressed: Qing Yang, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511; E-mail: qing.yang@yale.edu. †Abbreviations: FDA, Food and Drug Administration; BMI, body mass index. Keywords: artificial sweeteners, non-caloric, obesity, food reward, postingestive effects, saccharin, aspartame, sucralose, acesulfame K, neotame, sugar, weight gain 101