Title: Alternative Sweeteners

5
Cyclamate
Barbara A. Bopp
TAP Pharmaceutical Products, Inc., Deerfield, Illinois
Paul Price
Price International, Libertyville, Illinois
I. INTRODUCTION
Cyclamate (Fig. 1) was synthesized in 1937 by a University of Illinois graduate
student, Michael Sveda, who accidentally discovered its sweet taste (1, 2). The
patent for cyclamate eventually became the property of Abbott Laboratories,
which performed the necessary studies and submitted a New Drug Application
for the sodium salt in 1950. Cyclamate was initially marketed as tablets that were
recommended for use as a tabletop sweetener for diabetics and others who had
to restrict their use of sugar. In 1958, after enactment of the Food Additive
Amendment to the Food, Drug, and Cosmetic Act, the Food and Drug Administration
(FDA) of the United States classified cyclamate as a GRAS, or Generally
Recognized as Safe, sweetener. A mixture of cyclamate and saccharin, which
had been found to have synergistic sweetening properties and an improved taste
(3, 4), was subsequently marketed for use in special dietary foods. When soft
drinks sweetened with the cyclamate–saccharin mixture became popular in the
United States during the 1960s, the consumption of cyclamate increased dramatically.
Prompted by the growing use of cyclamate, additional studies were initiated.
It was found that cyclamate could be metabolized to cyclohexylamine (Fig.
1) by bacteria in the intestine (5). Then in 1969, the results of a chronic toxicity
study with a 10:1 cyclamate–saccharin mixture were interpreted as implicating
cyclamate as a bladder carcinogen in rats (6). Cyclamate was removed from
GRAS status (7), its use was initially restricted, and then in 1970, it was banned
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