Cyclamates and Alitame

As already noted, the FDA has approved five non-nutritive sweeten­ers just discussed: saccharin, aspartame, acesulfame-K, sucralose, and neotame. Others, however, have been developed and are under consideration by the FDA, the two most important of which are cy-clamates and alitame. The discovery of the cyclamates yields yet another fantastic story in the history of artificial sweeteners. In 1937 Michael Sveda, then a graduate student at the University of Illinois, was carrying out research on the synthesis of antipyretic drugs (drugs that control fever). He was smoking at the time (a practice that would not be allowed today!) and, at one point, brushed some loose threads of tobacco from his lips. As he did so, he noticed a very sweet flavor on the cigarette. With a little thought and analysis, Sveda was able to identify the source of that sweetness, a substance belonging to a class of compounds known as cyclamates.

Two cyclamates eventually found use as artificial sweeteners, sodium and calcium cyclamate. The generic term cyclamate is used for either of the two compounds. The structural formulas for sodium and calcium cyclamate are given below.

The two compounds are also known by a number of synonyms, most commonly sodium cyclohexylsulfamate and calcium cyclohex-ylsulfamate, respectively.

Sveda eventually applied for a patent for his discovery, which he later sold to Dupont. Dupont, in turn, sold the patent for cyclamates to Abbott Laboratories, which petitioned the FDA for approval of the sweetener in 1950. Abbott's initial interest in cyclamates was to mask the bitter taste of certain drugs it produced. The company later extended its petition to include the use of cyclamates as sweeteners for diabetics and others who had to limit their intake of sugar.

,0

NH-SO3

Na

Sodium cyclamate

2

Calcium cyclamate

© Infobase Publishing

Chemical structures of two cyclamates

In 1958 the FDA approved Abbott's petition and listed cyclamates as a GRAS substance, making it available for use in a wide range of products. Almost immediately, soft drink manufacturers began to use cyclamates as a sweetener in their products, sometimes by itself and sometimes in association with saccharin.

The success of cyclamates in the artificial sweetener market was, however, short-lived. In 1969 a group of researchers reported that rats fed a diet that included the commercial sweetener Sucaryl were very likely to develop bladder cancer. Sucaryl is a mixture contain­ing nine parts of cyclamate to one part of saccharin. Critics of the research questioned the value of the results, however, since the rats were fed an extraordinary amount of Sucaryl (equivalent to the quantity found in about 800 cans of soda pop) for nearly their whole lives. However, officials of the FDA were sufficiently concerned to ban the sale of cyclamates in the United States until further studies confirmed the product's safety for humans.

Those studies went on for more than a decade, culminating in a 1984 report by the Cancer Assessment Committee of the FDA that concluded that cyclamates are not carcinogenic. A year later, this finding was confirmed in an independent evaluation of the report by the National Academy of Sciences.

These studies have convinced regulatory agencies in a number of countries that cyclamates pose no threat to human health, and the product has now been licensed for use in more than 50 countries, including Canada, Denmark, Sweden, Belgium, the Netherlands, Switzerland, and Israel. The FDA is still considering its position on cyclamates, however. One ongoing concern is that, while the compounds may not actually cause cancer, they may promote the growth of cancers that develop in other ways.

Alitame is an artificial sweetener developed by chemists at the Pfizer pharmaceutical company in the 1980s. It is a dipeptide like aspartame except that it consists of the amino acids aspartic acid and alanine rather than aspartic acid and phenylalanine. Alitame has a number of advantages over aspartame. It is about 10 times as sweet as aspartame; it has no unpleasant aftertaste; it survives high tempera­tures better than aspartame; and, because it lacks phenylalanine, it presents no health hazards for people with phenylketonuria. Pfizer filed a petition with the FDA in 1986 seeking approval for alitame as a food additive, but as of 2006, no action has been taken on that petition. The compound is available under the brand name Aclame in a number of other countries, including Australia, Mexico, New Zealand, and the People's Republic of China.

The development of artificial sweeteners has been a great advan­tage for people with diabetes and those who are trying to control their weight. They make it possible for such individuals to enjoy sweet foods without worrying about harmful side effects, such as diabetic reactions and obesity. The use of artificial sweeteners is not entirely beneficial, however, as some products may cause allergic reactions ranging from the unpleasant but harmless to life threatening. Users of artificial sweeteners should be aware of potential health risks and use such products accordingly.