Artificial Sweetener Cyclamate Is Introduced

Date June, 1950

Abbott Laboratories launched the artificial sweetener Sucaryl, which contained the sodium salt of cyclamic acid or cyclamate. Du Pont marketed a similar product called Cyclan.

Also known as Sucaryl; Cyclan

Locale Illinois

Key Figures

• Michael Sveda (1912-1999), American chemist

Summary of Event

The first synthetic sugar substitute, saccharin, was developed in 1879. It became commercially available in 1907 but was banned for safety reasons in 1912. Sugar shortages during World War I resulted in its reintroduction. Two other artificial sweeteners, Dulcin and P-4000, were introduced later but were banned in 1950 for causing cancer in laboratory animals.

In 1937, Michael Sveda was a young chemist working on his Ph.D. at the University of Illinois. A flood in the Ohio valley had ruined the local pipe-tobacco crop, and Sveda had been forced to smoke cigarettes. While at his laboratory bench, where he was working on fever-depressant compounds, Sveda brushed some loose tobacco from his lips and noticed that his fingers tasted sweet. Having a curious, if rather foolhardy, nature, Sveda tasted the chemicals on his bench to find which one was responsible for the taste. The culprit was the forerunner of cyclohexylsulfamate, the material that came to be known as cyclamate. Sveda had time on his hands, because the starting materials he needed for his fever-depressant work were out of stock, and he had the chance to work with the sweetener. Later, on reviewing his career, Sveda explained the serendipitous discovery with the comment, “God looks after damn fools, children, and chemists.”

Sveda had not planned a career in industry; he intended to teach chemistry when he received his doctorate. “I was married and already had a youngster, so I had to go to work,” he said. Sveda joined the Du Pont Corporation in 1939 and assigned the patent for cyclamate to his employer. In June of 1950, after a decade of testing on animals and humans, Abbott Laboratories announced that it was launching Sveda’s artificial sweetener under the trade name Sucaryl. Du Pont followed with its sweetener product, Cyclan.

A Time magazine article in 1950 announced the new product and noted that Abbott Laboratories had warned that because the product was a sodium salt, individuals with kidney problems should consult their doctors before using the additive. Cyclamate dissolves readily in water, is very stable, and is unaffected by temperatures up to 500 degrees Celsius, certainly well beyond that to which foodstuffs would be exposed. Therefore, food containing the sweetener would have a long shelf life and cyclamate could be used like sugar in cooking. It has no calorific value, but is thirty to forty times sweeter than sugar. Unlike saccharin, cyclamate is sweet, with no unpleasant aftertaste. The additive was also found to improve the flavor of some foods, such as meat, and was used extensively in curing processes.

In the decade after cyclamates were introduced, their production rose to ten thousand tons per year, enough to sweeten fifty billion cups of coffee. By 1969, about 250 food products contained cyclamate, including cakes, puddings, canned fruit, ice cream, salad dressings, and, its most important use, carbonated beverages. It was estimated in the late 1960’s that 175 million Americans had cyclamate as part of their diet.

Cyclamates originally were considered harmless, because they were excreted unmetabolized from the body. In 1959, the chemical was added to the GRAS (“generally recognized as safe”) list of the Food and Drug Administration (FDA). Materials on this list, such as sugar, salt, pepper, and vinegar, do not have to be rigorously tested before being added to food. As late as 1965, the FDA reported that “there is no evidence that cyclamates at their present levels are a hazard to health.”

In 1964, however, publication of a report citing evidence that cyclamates and saccharin taken together provided a health hazard raised alarm in the scientific community. Numerous investigations followed. The debate surrounding this chemical became acrimonious, with claims and counterclaims between scientists, federal agencies, and the major supplier of cyclamate, Abbott Laboratories. The sugar industry was concerned that the newly developing diet food market would cut into its business. In 1967, a spokesperson from the New York Sugar Research Foundation indicated that the industry stood to lose $1 billion by its own estimate, and commented, “That’s a big prize to fight to keep.” This foundation alone had spent $500,000 over two years to support research into the safety of cyclamates. Abbott, for which cyclamate provided $14 million per year in profits (4 percent of the company’s business) insisted that its extensive tests had shown no evidence of harm at the levels usually consumed.

Initially, the claims against cyclamate had been that it caused diarrhea or interfered with drug action. By 1969, the focus had moved to cancer. Ironically, the evidence that sealed the fate of the artificial sweetener was provided by Abbott itself. A private Long Island, New York, company was commissioned by Abbott to conduct an extensive toxicity study to determine the effects of long-term exposure to the cyclamate-saccharin mixtures often found in commercial products. The company’s scientists had been feeding rats doses of the mixture between five hundred and twenty-five hundred milligrams daily to study its effects on reproduction, fetuses, and fertility. In each case, the rats were declared to be normal. When the rats were killed at the end of the study, however, those that had been exposed to the higher doses showed evidence of bladder tumors. Abbott shared the report with investigators from the National Cancer Institute and then with the FDA.

The report showed that the doses required to produce the tumors were equivalent to an individual drinking 350 bottles of diet cola per day, 100 to 120 times greater than even avid users of cyclamate consumed. A six-person panel of scientists was convened to review the data and urged the ban of all cyclamate from foodstuffs. On October 18, 1969, amid enormous media coverage, Robert Finch , U.S. secretary of health, education, and welfare, announced that cyclamate was to be withdrawn from the market by February 1, 1970. The ban was made official after Finch’s announcement was published in the Federal Register three days later. FDA commissioner Herbert Ley, Jr., then removed cyclamate from the FDA’s GRAS list on October 30.

Cyclamate is absorbed into the blood through the upper intestine. If cyclamate remains in the lower intestine, it can be converted to cyclohexylamine by naturally occurring bacteria. It is this conversion to cyclohexylamine that is most often cited as the basis of the risk to public health. Between 20 and 30 percent of the population can metabolize cyclamate to cyclohexylamine. Of this group, 90 percent metabolize only 0.1 percent of their daily intake; however, 4 percent of consumers are able to metabolize larger quantities of cyclamate. It is this population that is considered at risk.

In the years following the ban, the controversy continued. Doubt was cast on the results of the independent study linking sweetener use to tumors in rats, because the study was not designed to evaluate cancer risks but to develop long-term toxicity data. Bladder parasites, known as nematodes, found in the rats may have affected the outcome of the tests. In addition, an impurity, orthotoluenesulfonamide, found in some of the saccharin used in the study, may have led to the problems observed. When these other factors were removed, the results from the earlier tests could not be reproduced.

Extensive investigations such as the three-year project conducted at the National Cancer Research Center in Heidelberg, Germany, found no basis for the widespread ban. The major concern for many researchers during this period was not the threat of cancer but the fact that large doses of cyclohexylamine, the product formed from cyclamate by a small percentage of the population, had caused the testes of rats to shrink. In studies in the early 1970’s, rats fed high doses of saccharin alone were found to have developed bladder tumors. In 1996, twenty-seven years after its removal from the GRAS list, cyclamate was added back to the list, after further studies failed to show that it causes cancer in humans. An outright ban was averted by labeling laws that required disclosure of information to the consumer on products containing saccharin.

Significance

The introduction of cyclamate heralded the start of a new industry. For individuals who had to restrict their sugar intake for health reasons, or for those who wished to maintain or lose weight for cosmetic purposes, there was now an alternative to giving up sweet food and drink.

The original ban of the sweetener was accompanied by something of a media circus. The New York Times showed pictures of concerned housewives standing next to large displays of diet drinks. Newsweek published a photograph of a bulldozer in Toronto crushing thousands of cans of Canada Dry. Prior to the ban, most diet drink companies had been working on cyclamate-free formulations for their products. The Pepsi-Cola company scored a coup by having a new diet drink formulation on the market almost as soon as the ban was instituted. In fact, the company ran advertisements the day after the ban was announced showing the Diet Pepsi product boldly proclaiming “Sugar added—No Cyclamates” with the byline “Pepsi-Cola Company cannot in good conscience offer its customers any product about which even the remotest doubt exists.”

Sveda, the discoverer of cyclamates, was not impressed with the FDA’s decision on the sweetener and subsequent investigations. He accused the FDA of “a massive cover-up of elemental blunders” and claimed that the original ban was based on sugar politics and bad science. The situation was further complicated by the strenuous efforts of a number of consumer activist groups such as Ralph Nader’s organization. In 1982, the FDA was sufficiently concerned over the validity of the data that promoted the ban originally that it instituted a yearlong study by the National Academy of Sciences. The report issued by this group concluded that cyclamate itself does not cause cancer but raised issues that left the safety of the sweetener in dispute. The committee stated that there was “suggestive evidence” that cyclamate was a tumor promoter, or cocarcinogen. In addition, it was noted that, used in combination with saccharin, cyclamate may cause an increased risk of bladder cancer. In the light of this report, the FDA decided not to reverse its earlier decision.

The scientific community appears split on the cyclamate question. It seems unlikely that the FDA, which is sensitive to criticism leveled by the concerned public over its dealings with a number of new drugs and foodstuffs, will reverse the decision. For the manufacturers of cyclamate, the problem lies with the wording of the Delaney clause, a 1958 amendment to the Food, Drug, and Cosmetic Act of 1938, which regulates new food additives. The amendment states that the manufacturer must prove that its product is safe, rather than the FDA having to prove that it is unsafe. The onus was on Abbott Laboratories to deflect concerns about the safety of the product, and it remained unable to do so.

Bibliography

“Bitter Battle Over Sweets.” Science News 92 (August 26, 1967): 199-202. A nontechnical article outlining the development of the cyclamate industry. Cites research supported by the Sugar Foundation. Animal studies performed by the Wisconsin Alumni Research Foundation, which linked the sweetener to inhibited growth and infertility in some laboratory rats, are discussed.

Cohen, Rich. Sweet and Low: A Family Story. New York: Farrar, Straus and Giroux, 2006. A history of the family business that manufactures the artificial sweetener “Sweet’N Low,” made from granulated saccharine and dextrose.

“Cyclamates Try for a Comeback.” BusinessWeek, August 6, 1984, 24. A nontechnical article chronicling the continued efforts by the sweetener industry to have cyclamates reinstated as a food additive.

Gardner, David W. “Bitter News About Sweeteners.” The New Republic, September 14, 1968, 17-18. This article weighs some of the evidence supporting the harmful effects of cyclamates. Questions the policy that allowed the introduction of the sweetener in the 1950’s.

Miller, William T. “The Legacy of Cyclamate.” Food Technology, January, 1987, 116. A concise, nontechnical overview of the political and scientific history of cyclamates from their discovery in 1937 to the 1987 report by the Food and Drug Administration. Very little detail, but reports that a petition for reintroduction of the cyclamate products made by the sweetener industry in 1982 had been denied by the FDA.

Nabors, Lyn O’Brien, ed. Alternative Sweeteners. 3d rev. ed. New York: M. Dekker, 2001. A comprehensive, updated examination of alternatives to sucrose. Includes discussions of the science of sweeteners, their health effects, and industry regulation. The author is affiliated with the Calorie Control Council, a nonprofit group that, according to its Web site, represents “the low-calorie and reduced-fat food and beverage industry.”

Storm, Jackie. “The Sweet Truth.” Women’s Sports & Fitness 9 (December, 1987): 12-13. Aimed at the nonscientist, this article discusses the relative nutritional merits of various natural and synthetic sweeteners and the controversy surrounding the introduction of aspartame. Brief reference to cyclamates.

Sun, Marjorie. “Cyclamate’s Safety Still Unresolved.” Science 228 (June 28, 1985): 1514-1515. A short discussion of the National Academy’s report on their yearlong investigation of the experimental evidence linking cyclamates to dangerous health effects.

Turner, James T. “Cyclamates.” In The Chemical Feast. New York: Grossman, 1970. An inflammatory indictment of the Food and Drug Administration. A sensational chapter from a best-selling book that provides one of the few sources of information about events that led up to the banning of cyclamates in 1969.