Saccharin is the oldest artificial sweetener. It was discovered by Ira Remsen and Constantine Fahlberg of John Hopkins University while working on coal tar derivatives and is about 300 times as sweet as sucrose. Saccharin is not digested by the body and goes directly through the human digestive system. Therefore, it does not affect blood insulin levels, and has effectively no food calories. At the time it was discovered, it was an important sugar replacement for diabetics. It is commonly known under the brands Sweet n’ Low and others.
Saccharin has always been surrounded by controversy. As early as 1907, the public was concerned over its safety and proposed banning it. Theodore Roosevelt, a diabetic, fought the idea. He said, “My doctor gives it to me every day…Anybody who says saccharin is injurious to health is an idiot” (Corcoran 12). Despite these stirring words of reassurance, some stubborn people remained unconvinced.
In 1912, saccharin was briefly banned in the US due to concerns about its safety. This ban was lifted 5 years later with the advent of the First World War (Saccharin history). As so frequently happens when a nation has to buckle down for a protracted war, resources in the US had to be rationed in order to provide for the troops abroad. One of those resources was table sugar. As more and more US sugar was being sent across the ocean to the soldiers in Europe, the sweetening needs of the populace at home were met with cheap and plentiful saccharin.
By the time the war ended, America and its European allies had grown quite fond of the new sweetener. Usage of saccharin leveled off when sugar became available once again, but it had entered the scene to stay. World War II again brought sugar rationing and a dramatic increase in saccharin usage, which this time did not decline with the war’s end. However, during that period, saccharin took on second-place status as cyclamate, another artificial sweetener discovered in 1937, came on the scene.
Scientists suggested that saccharin might be a carcinogen in 1951. In 1958, however, saccharin was added to the GRAS (Generally Recognized as Safe) list.
That same year, 1958, Marvin Eisenstadt, owner of Cumberland Packing Company in Brooklyn, NY, introduced Sweet‘n Low, which mixed saccharine with cyclamate (to counter the metallic aftertaste of saccharin) in the small packet form that we still know today. The present formula has abandoned the cyclamate, but the main ingredient is still saccharin.
During this entire period of saccharin’s history, the FDA allowed the makers of saccharin (and cyclamate) to determine for themselves whether it was a safe product for human consumption (www.btinternet.com/~amcbryan/aspartame/comment1a.htm). Indeed, the FDA showed very little interest in saccharin until 1969, when researchers discovered that cyclamate was carcinogenic in laboratory mice. Cyclamate was banned by the FDA that same year (http://web1caryacademy.org/chemistry/rushin/ StudentProjects/CompoundWebSites2001/Saccharin/BITTERSWEET.htm).
The FDA proposed also banning saccharin until conclusive tests could prove its safety. This suggestion was met with significant opposition from a public, which had become greatly enamored with the concept of artificial sweeteners and had just lost their only other option at the time, cyclamate.
In 1972, the results of a long-term study showed that rats fed saccharin had developed bladder tumors. Subsequently, the Food and Drug Administration (FDA) removed saccharin from GRAS status and issued a regulation limiting the use of saccharin in foods.
Then in 1974, a National Academy of Science review found that, “Saccharin itself could not be identified as the cause of the tumors because of possible impurities as well as problems with experimental design and procedures” (Kennedy 131). Therefore, the FDA decided not to ban saccharin until they received the results of a study being conducted in Canada.
In March 1977, the Canadian study showed that feeding large doses of saccharin to pregnant rats and their weanlings produced bladder cancers in the male offspring. The Canadians immediately banned saccharin.
When the FDA announced its intentions to follow suit, the U.S. Congress overturned the FDA’s action and voted for an eighteen-month moratorium. The U.S. Congress requested more time to evaluate the results of the study. Shortly thereafter, Congress enacted the Saccharin Study and Labeling Act, which stayed the FDA’s hand temporarily and ordered a warning label on all saccharin products: “Use of this product may be hazardous to your health. This product contains saccharin which has been determined to cause cancer in laboratory animals” (Brody 482-483).
During 1978 and 1979, the National Cancer Institute and FDA conducted a population-based study on the possible role of saccharin in causing bladder cancer in humans. In general, people in the study who used an artificial sweetener had no greater risk of bladder cancer than the population as a whole. However, when only the data for heavy users was examined, there was some suggestive evidence of an increased risk, particularly in persons who consumed both diet drinks and sugar substitutes and who used at least one of these two forms heavily(Carcinogenicity).
In the study, heavy use was defined as merely six or more servings of sugar substitute or two or more 8-ounce servings of diet drink daily. Consequently, several studies have found that people with bladder cancer were more likely to have eaten food that contained saccharin than were people who didn’t have bladder cancer.
The National Cancer Institute compared the diets of 5,800 similar people who were disease-free to the diets of 3,000 men and women with bladder cancer. Those who reported consuming high levels of saccharin on a daily basis were found to be at a higher risk for association to poorly differentiated bladder tumors (Corcoran 13).
Saccharine is the most widely used sugar substitute in the world, and yet we still do not fully understand its effects on the human body. Drinking one can of diet soda per day can increase the risk of bladder cancer by sixty percent (Goulhart). The fact that it has never been conclusively proven to cause cancer in humans does not make saccharin safe.
Epidemiological studies
The question of whether saccharin consumption increases the risk of bladder cancer in humans takes on added importance considering the increasing incidence of that cancer in recent decades. Bladder cancer is now the fifth most common cancer in the United States. The National Cancer Institute estimates that 54,500 new cases of bladder cancer would occur in 1997. Between 1973 and 1994, the incidence of bladder cancer increased by 11.3% in males and 14.7% in females. National Cancer Institute, SEER, Cancer Statistics Review, 1973-1994. The reasons for those increases in men are not known.
Numerous case-control studies have sought to evaluate the relationship between artificial-sweetener consumption (saccharin and cyclamate were generally used together under the brand name Sweet n’ Low and others) and the incidence of bladder cancer. Several studies, including some of the largest ones, found significant increases in rates of bladder cancer.
National Cancer Institute (3,010 total cases) found relative risks of between 1.6 and 3.0 in several subgroups of Americans, including low-risk white females and heavy-smoking males.
Sturgeon et al’s analysis (1,860 cases) of the NCI data found that heavy use of artificial sweeteners was associated (RR(Relative Risk) = 2.2) with higher-grade, poorly differentiated bladder tumors.
Howe et al (632 cases) found an increased risk in Canadian males (RR = 1.6); men who consumed more artificial sweeteners or consumed artificial sweeteners for a longer period of time had relatively high risks.
Cartwright (622 existing cases; 219 new) found an increased risk (RR = 2.2) in British non-smoking males, but not females.
Morrison and Buring (592 male and female patients with lower-urinary-tract cancer — 94% of whom had bladder cancer) found increased risks in women who consumed dietetic beverages (RR = 1.8 [1.0-3.3]) and who consumed sugar substitutes (RR = 1.9 [1.0-3.6]) (stratified for age and smoking history). Women who consumed dietetic beverages for five years or more had a relative risk of 3.7.
Morrison (555 British cases) found an increased risk (RR = 2.3) in British females (but not males or Japanese cases) who consumed more than 10 tablets of sugar substitutes (primarily saccharin) a day.
Mommsen’s small study (47 female cases) in Denmark found increased risks in all women (RR = 6.7) and in nonsmoking women (RR = 3.3).
That some studies did not detect an increased risk could be real or due to the limited duration of subjects’ exposure to artificial sweeteners — particularly in light of the long latency period for cancer and the limited consumption of saccharin in the U.S. before the mid 1960s (many subjects were exposed for under 15 years in the U.S. studies) — lack of exposure in utero, small numbers of cases and limited power to detect small risks, and loss of sensitivity due to lumping occasional users of artificial sweeteners in with heavy users. Those and other limitations reduce the likelihood that saccharin’s link to a higher rate of bladder cancer could be detected.
Furthermore, no epidemiologic research has evaluated whether saccharin might cause tumors at sites other than the urinary bladder, despite known differences in organ specificity between species in the case of most carcinogens. In light of several rodent studies documenting higher rates of cancer in other organs, that absence of information is troubling and suggests the need for more research. New research would also benefit from the increased duration of exposure to saccharin.
Thus, in numerous studies, artificial-sweetener consumption was associated with significant increased risks of bladder cancer, though there were inconsistencies in risks to men and women. Some (mostly smaller) studies did not find an association. The NTP( National Toxicology Program) acknowledges that “a small increased risk in some subgroups, such as heavy users of artificial sweeteners, cannot be definitely excluded.” That is an understatement that could have been expressed equally accurately as: Several studies found an increased risk in some subgroups, and it is the subgroup of heavy consumers about whom we should be especially concerned.
The studies, such as West, Sheldon, et al, showing that saccharin can act as a promoter should suggest extra caution. In laboratory studies, animals are kept as healthy as possible and are studiously protected from substances in their food, water, and air that might, together with saccharin, increase the incidence of cancer. In sharp contrast, human consumers of saccharin are exposed to a wide range of environmental and occupational toxins, suffer diseases ranging from alcoholism to malnutrition, and often consume for many years diverse legal (tobacco and alcohol) and illegal drugs. Any of those factors might enhance the carcinogenicity of saccharin in a subgroup of consumers, whose genotypes span a much wide range.
Saccharin was evaluated by the Joint Expert Committee on Food Additives in 1967, 1974, 1978 and 1980. In 1978, the Committee changed the ADI(Acceptable Daily Intake) from 5 mg/kg to a temporary ADI of 2.5 mg/kg and withdrew the conditional ADI of 15 mg/kg for dietetic purposes only. The decision to reduce the ADI and to restrict the use of saccharin was based primarily on the results of animal studies, which indicated that excessive and long-term ingestion of saccharin was potentially a carcinogenic hazard for humans. At the 1980 meeting the temporary ADI of 2.5 mg/kg was extended until 1984 and required the submission of the results of a long-term feeding study in rats and epidemiological studies.
Per the committee, the principal adverse effects that have been reported from saccharin are as follows:
Mild digestive disturbances were noted by Herter & Folin (1911) in volunteers ingesting doses of 1-1.5 g of saccharin/day. Loose stools were observed in clinical studies when subjects consumed cyclamates plus saccharin in doses of about 7 g/day (Berryman et al., 1968). At these dosages, the saccharin intake was about 0.7 g/day. Evidence from other studies indicates that cyclamate alone at intakes of 5-7 g/day may cause loose stools.
Allergic responses, principally skin reactions of a phototoxic or photosensitivity type occur but appear to be of low incidence and, in some cases, may have been due to cyclamate being ingested at the same time (Fujita et al., 1965; Stritzler & Samuels, 1956; Kingsley, 1966;Boros, 1965; Meisel, 1952; Gordon, 1972; Taub, 1972). Some authors have suggested that there may be a cross-sensitivity to sulfonylureas and similar drugs known to cause phototoxic skin reactions. Contact dermatitis and photosensitivity or phototoxic reactions have not been noted in persons occupationally exposed to saccharin (NAS, 1974).
The Journal of the National Cancer Institute of January 7, 1998, reported results of long-term saccharin tests on monkeys and used the opportunity to raise fundamental questions about the value of animal safety tests.
“Mice do not get cancer from eating saccharin. Neither do hamsters, guinea pigs, nor, for that matter, monkeys, according to the latest series of tedious long-term tests. Monkeys fed saccharin in baby bottles as infants and mixed with bread as adults in tests lasting from 6 to 25 years showed no cancer risk.
An accompanying editorial, however, criticized the study’s choice of dosages, species, and numbers, and reminded readers of the need for reducing, refining, and replacing animal tests. None of these tests has been able to trump human epidemiologic studies, which show none of the effects seen in rats.
Animal tests have not proven whether the artificial sweetener is safe or not, but they have clearly shown that the tests themselves are undependable. They are also expensive. A single test of one product in one rodent species takes several years and costs well over one million dollars.” (Takayama S, Sieber SM, Adamson RH, et al. Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. J Natl Cancer Inst 1998;90:19-25; Zurlo J, Squire RA. Is saccharin safe? Animal testing revisited. J Natl Cancer Inst). http://www.pcrm.org/magazine/GM98SpringSummer/GM98SpSm10.html1998;90:2-3
The Calorie Control Council, established in 1966, is an international association representing the low-calorie and diet food and beverage industry. It nominated saccharin for delisting following the controversial animal studies, which led to a new review of the carcinogenicity data for saccharin.
Saccharin had been listed in the NTP Report on Carcinogens as “reasonably anticipated to be a human carcinogen” since 1981. The basis for the this listing was sufficient evidence of carcinogenicity in experimental animals. Saccharin was removed from the report after the NTP review determined that the rodent cancer data are not sufficient to meet the current criteria to list saccharin in the Report as a “reasonably anticipated human carcinogen.” NTP based the determination on the observation that bladder tumors in rats arose from mechanism that are not relevant to humans.
In May 2000, the NTP(National Toxicology Program) released the 9th edition of its Report on Carcinogens and announced that saccharin had been delisted.
The final decision was based on the recommendation of Dr. Kenneth Olden, Director of the National Institute of Environmental Health Sciences and the National Toxicology Program, who said, “Two decades ago, when saccharin was shown to produce bladder tumors in rats, it was a prudent, protective step to consider the sweetener to be a likely human carcinogen. However, our understanding of the science has advanced and allows us to make finer distinctions today. “
Studies now indicate that the rat bladder tumors arise from mechanisms that are not relevant to the human situation. In addition, we have decades more data from observations of humans using saccharin that adds to our confidence. In other words, with better science we can now make a better call.”
The decision was also endorsed by U.S. Secretary of Health and Human Services Donna Shalala. The NTP report was submitted to Congress.
On December 21, 2000, President Clinton signed a bill that removed the warning label that had been required on saccharin-sweetened products since 1977.
Not all scientists agree with saccharin’s upgraded safety rating. There are concerns that saccharin’s review was corrupted by industry influence. Michael Jacobson, executive director of The Center for Science in the Public Interest (CSPI) charges that long-time defenders of saccharin dominated IARC ‘s (International Agency for Research on Cancer) 26-member committee. He states that half of the participants in the meeting were tied to industry. A key committee member was Samuel Cohen, a University of Nebraska researcher whose studies on saccharin were relied upon heavily by IARC for its decision. Cohen’s research has been funded, in part, by the International Life Sciences Institute (ILSI), an industry group whose sponsors include Cumberland Packaging (maker of Sweet ‘N Low saccharin products), Coca-Cola, and PepsiCo.
In a December 1998 letter to, Secretary of Health and Human Services, Donna Shalala, Jacobson stated that IARC’s evaluation was inadequate from a scientific standpoint:
It summarily dismissed the evidence from an NCI (National Cancer Institute) study — the largest and most-sensitive human study ever done — that found links between artificial-sweetener consumption and bladder cancer.
It dismissed evidence from animal studies that saccharin increases the potency of chemical carcinogens. It accepted completely industry’s theory (based largely on research conducted by committee member Cohen and financed in part by ILSI) that saccharin causes cancer in the urinary bladders of male rats by a mechanism, and only by that one mechanism, that is irrelevant to humans.
It ignored evidence that saccharin causes tumors in animals at sites other than the urinary bladder. (http://www.cspinet.org/new/Shalala_letter_12_10_98.htm)
Early the following year, saccharine was delisted by the NTP. When Congress proceeded with plans to remove the warning label from saccharin more protests arose. Rather than proceeding through normal approval channels lawmakers opted to move this piece of legislation through the appropriations process, which does not allow for substantive inquiries and hearings. Lawmakers generally oppose legislating through this process however did not have such qualms when Health and Human Services Appropriations Bill (HR 4577) eliminated the warning label on products containing saccharin. (http://www.cspinet.org/news/saccharin_labeling.html)
CSPI”s Jacobson states “The evidence for saccharin is mixed, with some studies indicating it causes cancer and others suggesting it doesn’t. In light of the uncertainty, officials concerned about the public health should continue to consider saccharin a potential carcinogen and not do anything that would increase it’s use. Doing otherwise would only jeopardize consumer health.
When a dollar’s worth of saccharin will do the sweetening of twenty dollar’s worth of sugar you can be sure the mega diet and beverage industries have a tremendous interest in the outcome of safety data of artificial sweeteners, like saccharin.
With the data unclear, and the restrictions on saccharin removed, there is no incentive for further studies especially, independent ones. Society will be waiting for the results of the ultimate human test. One that has been taking place since saccharine was invented in 1879. Saccharin did not become widely used until thirty years ago, and bladder cancer takes decades to develop; the near future holds the definitive answer about its safety.
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