We owe the discovery of several artificial sweeteners to a few brave scientists who violated the code of laboratory hygiene and tasted their samples, often inadvertently [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 intake” to “for use in people who desire to limit sugar intake” [7
]. Saccharin is about 300 times sweeter than sucrose but has a bitter aftertaste. Cyclamate, which was discovered in 1937 by Michael Sveda at the University of Illinois [8
], was often blended with saccharin to improve the taste. Both compounds were deemed “generally recognized as safe” in the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetics Act. After the Food and Drug Administration (FDA) banned cyclamate in 1969 because of its carcinogenic potentials, concern about saccharin’s safety also intensified. Eventually, the FDA announced its intention to ban saccharin in 1977. Avid consumer protests led to a moratorium from Congress on the final ban decision. A warning label was nonetheless required on all saccharin products. Subsequent studies refuted the link between cyclamate and cancer [9
]. Bladder cancer associated with saccharin ingestion was also found to be specific to rodent physiology [9
]. Cyclamate continues to be marketed in about 50 countries, including Canada. The saccharin warning label was removed in 2000.
Even though saccharin stayed on the U.S. market, regular artificial sweetener users were relatively few until the next generation of compounds arrived (, orange line) [2
]. Rigorous safety testing preceded FDA approval for those new artificial sweeteners. In 1965, James Schlatter at Searle discovered aspartame [10
]. He was trying to make new ulcer drugs. Aspartame consists of two amino acids, phenylalanine and aspartate, linked to a methanol backbone (). Unlike the other artificial sweeteners that are usually excreted unchanged, aspartame can be metabolized. Therefore, it is not strictly non-caloric (4 Kcal/g) and forbidden in people with phenylketonuria [9
]. Aspartame is about 200 times sweeter than sucrose. Due to the small amount ingested at a time, its caloric contribution is negligible. The FDA approved aspartame first for use in dry foods in 1981, then as a general sweetener in 1996. Monsanto bought Searle and converted it into NutraSweet in 1984. The patent on aspartame expired in 1992. Amid competition from generic manufacturers, NutraSweet engineered neotame, which was approved in 2002 [11
]. Neotame is the most potent sweetener on the market, at 7,000 times the sweetness of sucrose.
Figure 2 Structures of sucrose, a natural caloric sweetener, and various artificial sweeteners. Source: Kroger et al.  and Brown et al .
Acesulfame potassium resembles saccharin and cyclamate in structure and taste (). Karl Clauss at Hoechst discovered 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 (). It was approved 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 increase in the number of food products containing non-caloric artificial sweeteners. More than 6,000 new products were launched in the United States between 1999 and 2004 (, purple line) [14
]. Currently, an ingredient search on foodfacts.com yields 3,648 products containing one or more of the five FDA approved artificial sweeteners. Sucralose is the most popular (1,500 products), followed by acesulfame potassium (1,103 products) and aspartame (974 products). Artificial 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 artificially sweetened items when making the day-to-day choices on food and beverages. The National Household Nutritional Survey estimated that as of 2004, 15 percent of the population 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 regular or sporadic, is probably much greater.