Yang: The neurobiology of sugar cravings 103 Figure 2. Structures of sucrose, a natural caloric sweetener, and various artificial sweeteners. Source: Kroger et al. [9] and Brown et al [25]. (Figure 2). Karl Clauss at Hoechst discov- ered it in 1967 [12]. The FDA approved its use in dry foods in 1988 and as a general sweetener in 2003. The most recent structural advance came in 1979, when Shashikant Phadnis, a graduate student working for Tate & Lyle, discovered sucralose [3]. It is synthesized from sucrose by substituting chlorine for three of its hydroxyl groups, generating 600 times the sweetness (Figure 2). It was ap- proved in 1999. Sucralose sales amounted to £148 million in 2008, generating 23 percent of Tate & Lyle’s total operating profit [13]. The last decade saw an explosive in- crease in the number of food products con- taining non-caloric artificial sweeteners. More than 6,000 new products were launched in the United States between 1999 and 2004 (Figure 1, top line) [14]. Currently, an ingre- dient search on foodfacts.com yields 3,648 products containing one or more of the five FDA approved artificial sweeteners. Su- cralose is the most popular (1,500 products), followed by acesulfame potassium (1,103 products) and aspartame (974 products). Ar- tificial sweeteners are most commonly used in carbonated drinks. They also are found in a variety of other products, from baby food (e.g., Pedialyte) to frozen food (e.g., Lean Pockets). With such a diverse selection, it is more likely that people will encounter artifi- cially sweetened items when making the day- to-day choices on food and beverages. The National Household Nutritional Survey esti- mated that as of 2004, 15 percent of the pop- ulation regularly were using artificial sweetener [2]. IRI Consumer Report stated that 65 percent of American households bought at least one sucralose-containing product in 2008. Therefore, the total number of artificial sweetener consumers, either reg- ular or sporadic, is probably much greater. DO ARTIFICIAL SWEETENERS AFFECT WEIGHT? Intuitively, people choose non-caloric artificial sweeteners over sugar to lose or maintain weight. Sugar provides a large amount of rapidly absorbable carbohydrates, leading to excessive energy intake, weight gain, and metabolic syndrome [15,16,17]. Sugar and other caloric sweeteners such as high fructose corn syrup have been cast as the main culprits of the obesity epidemic. Whether due to a successful marketing effort on the part of the diet beverage industry or not, the weight conscious public often con- sider artificial sweeteners “health food” [6].