Saccharin: bittersweet.

"It's been around a long time. I'm not concerned about the safety," says Josh Rosenbaum, a 27-year-old meeting planner in Washington, D.C. "Rats are one thing, people are another."

"I think of cancer in rats," says Amie Chant, an agribusiness consultant in McLean, Virginia. "I don't buy saccharin."

Ask anyone about saccharin and the mixed reactions seem to parallel the scientific debate. Twenty-one years after researchers confirmed that the sugar substitute causes cancer in animals, controversy still rages.

Are the little pink packets of Sweet'N Low--or the dozens of foods made with saccharin--safe for humans? The evidence is anything but reassuring.

"There are enough human studies that show increased incidence of bladder cancer," says epidemiologist Richard Clapp of Boston University's Department of Environmental Health. "We should be extremely cautious, because saccharin is consumed by a huge number of people."

But apparently not huge enough for the diet-food industry, which is trying to clear saccharin's name ... and increase its consumption.

Late last year, a panel of independent experts narrowly voted to keep the artificial sweetener on the government's list of "anticipated" or "likely" cancer-causing chemicals. The chief of the National Toxicology Program (the branch of the National Institutes of Health that keeps the list) must make a final recommendation to Health and Human Services Secretary Donna Shalala by fall.

If health officials decide to "delist" saccharin--and rumor has it they will--tens of millions of men, women, and children would be exposed to higher levels of an unsafe chemical.

Oldie, not Goodie 

Saccharin is the granddaddy of artificial sweeteners. It was discovered in 18 79 when a chemist at Johns Hopkins University in Baltimore noticed a sweet taste on his hands after working with some chemicals in the lab.

Food processors quickly embraced the substitute--it's about 300 times sweeter than sugar, and a dollar's worth of saccharin will do the sweetening of $20 worth of sugar. Saccharin had an early champion in Teddy Roosevelt, who in 1907 fought the first attempt to ban it over safety concerns.

"My doctor gives it to me every day," said Roosevelt, who had diabetes. "Anybody who says saccharin is injurious to health is an idiot."

While saccharin caught on briefly in the U.S. during the sugar shortages of World War I, it wasn't until the 1960s that it really took off. That's when a flood of diet foods like the soft drink Tab hit the market.

But the handwriting was on the wall. As early as 1951, research suggested that saccharin might be a carcinogen. In 1977, a study by the Canadian government showed that it causes bladder tumors in rats.[1]

That led the U.S. Food and Drug Administration to call for a ban. The feds' action spurred an uproar among dieters and diabetics, who said that they needed a cheap, powerful artificial sweetener. (Full-page newspaper ads by the diet-food industry's Calorie Control Council added pressure.) In a compromise, Congress put a moratorium on the ban but required that all foods containing saccharin carry warning labels (see photo).

The industry has spent the last 20 years trying to exonerate saccharin, which has largely lost the soft drink market to more-costly aspartame (NutraSweet, Equal). Aspartame doesn't have saccharin's bitter aftertaste ... and it doesn't bear a cancer warning.

The Animal Evidence

The diet-food industry admits that large amounts of saccharin cause bladder cancer in male rats. But that doesn't translate into cancer in people, it argues.

"As a result of extensive studies, it is clear that the mechanism that underlies the development of bladder tumors in the male rat fed sodium saccharin is unique to this sex and species and not relevant for humans," says the Calorie Control Council.

The industry's reasoning: Unlike human urine, the urine of male rats is high in protein. Large amounts of saccharin raise urine's sodium content and lower its acidity. That combination creates microscopic crystals (precipitates) that irritate the bladder and ultimately cause cancer.

"At first blush, the theory may appear attractive," says Emmanuel Farber, a pathology professor at Jefferson Medical College in Philadelphia and chairman of a 1978 National Academy of Sciences panel that concluded that saccharin causes cancer in animals. "But in fact it provides no evidence at the molecular level as to how saccharin--or the precipitates--actually cause cancer.

"If it's a carcinogen in animals, we need to assume it's so in man," he adds. "Why take a chance?"

What's more, other studies show that saccharin causes tumors not just in male rats' bladders, but in their lungs and other organs.[2] It also causes tumors in the bladders and other organs of female rats and mice of both sexes.[2]

And animals given cancer-causing chemicals get more tumors when they're also given saccharin.[3] That's especially troubling, since humans--unlike lab rats--are constantly assaulted by an array of carcinogens.

Saccharin supporters say that rats developed tumors only after being given huge amounts of saccharin--the equivalent of 800 cans of diet soda a day.

"It is a high-dose phenomenon," says the Calorie Control Council.

But scientists routinely test chemicals on animals at very high doses. It's the only practical way to predict a substance's impact on a large population without having to give millions of animals more human-like doses.

The Calorie Control Council's latest weapon: a new study, sponsored in part by the National Cancer Institute (NCI), in which 20 monkeys of three species were fed amounts of saccharin equivalent to about ten diet sodas a day for up to 24 years.[4] None of them got bladder cancer (though three got other cancers). The 16 monkeys in the control group--they weren't given saccharin--remained cancer-free.

But an editorial accompanying the study in the Journal of the National Cancer Institute questioned its relevance for humans.

"The small number of animals, the multiplicity of species, and the low doses of saccharin greatly reduced the sensitivity of the study to subtle effects," wrote Johns Hopkins University's Joanne Zurlo and Robert Squire (a former consultant to the Calorie Control Council). "The level of precision in the data ... was less than optimal, limiting the ability to extrapolate the results to humans."

Emmanuel Farber was more candid. "It is unfortunate that a distinguished journal would publish a study with so little scientific merit."

Human Studies

Since 1980, six studies have found that people with bladder cancer were more likely to have eaten foods with artificial sweeteners than were people who didn't have bladder cancer.

The largest and best, which was conducted by the NCI, compared the diets of 3,000 men and women with bladder cancer to the diets of 5,800 similar people who were disease-free.[5] Those who reported consuming three or more servings of sugar substitutes and two or more eight-ounce diet beverages a day had a 60 percent higher risk of bladder cancer. Nonsmoking women who consumed artificial sweeteners at least twice a day also had a 60 percent greater risk.

The study wasn't perfect. It couldn't distinguish between saccharin and the artificial sweetener cyclamate--both were often used together, and cyclamate, like saccharin, may increase the potency of cancer-causing chemicals.

But short of giving saccharin to people and waiting to see if they get cancer, that's about as good as the human evidence may ever get.

"We can't test cancer-producing agents in humans," explains Farber. "First of all, it would take 20 to 30 to 40 years. And who would we expose?"

Full Bladder

The National Cancer Institute estimates that there were 54,500 new cases of bladder cancer in 1997. That puts it fifth on the most-common list (behind the Big Four: prostate, breast, lung, and colon). Between 1973 and 1994, the bladder cancer rate climbed by 11 percent in men and 15 percent in women.

But researchers don't blame saccharin alone. Smoking raises bladder cancer risk, for example, which might explain why the disease is four times more common in men than in women. What's more, saccharin didn't hit the food supply in a big way until the 1960s, and bladder cancer can take 30 to 50 years to develop (although saccharin could act faster by promoting the effect of other carcinogens). And most researchers believe that saccharin is a relatively weak carcinogen.

"You can't say that saccharin is a major cause of bladder cancer," says NO epidemiologist Shelia Zahm. "But you cannot let it off the hook."

[1] Toxicol. Appl. Pharmocol. 52: 113, 1980.

[2] Environ. Health Perspectives 25: 173,1978.

[3] Fundam. Appl. Toxicol. 7: 585, 1986.

[4] J. Not. Cancer Inst. 90: 2, 19, 1998.

[5] Lancet i: 837, 1980.

RELATED ARTICLE: SWEET NOTHINGS

Who eats saccharin? Most of us, even if we never touch a packet of Sweet'N Low. The average American consumes enough saccharin to equal about seven pounds of sugar per person per year. It's in dozens of products, from Crest toothpaste and Listerine mouthwash to Robitussin cough syrup and Carefree chewing gum.

It's also in a small number of sugar-free soft drinks (mostly at restaurants and soda fountains), salad dressings, jams, jellies, preserves, and baked goods. Saccharin's major competitors:

* Aspartame (NutraSweet, Equal). It's become the sweetener of choice and is in everything from Diet Coke and Light Dannon Yogurt to Swiss Miss Fat Free Hot Cocoa Mix and BreathSavers. In 199 1, Americans ate enough to equal 17 pounds of sugar per person. The reason it hasn't completely taken over the artificial sweetener market: It's more expensive and it can't be heated. Some people maintain that aspartame causes headaches, but so far no connection has been proven. And some of the studies on aspartame and cancer--which were done in the 1970s--may have been flawed and should be repeated.

* Acesulfame K (Sunett). It's used as a tabletop sweetener and in dozens of foods, from Hershey's Lite Syrup and its Fat Free Dutch Chocolate Hot Cocoa to Trident gum and sugar-free Jell-O. It's often used together with aspartame. The German manufacturer has petitioned the FDA to approve acesulfame K (ACE-sull-fame-KAY), which is also known as acesulfame potassium, for use in soft drinks. The Center for Science in the Public Interest (Nutrition Action's publisher) has led an international group of scientists in opposing the move, because the only safety studies available were poorly done and they indicate that it may cause cancer.

RELATED ARTICLE: THE BOTTOM LINE

* Saccharin should be banned. It causes bladder and other cancers in rats and mice. In the best study in humans, bladder cancer patients were more likely to report being heavy users of artificial sweeteners.

* If you use Sweet'N Low or eat foods that contain saccharin, stop-or at least switch to foods made with aspartame (NutraSweet, Equal), which appears to be safer.

* For a more detailed look at the research on saccharin, visit our web site (www.cspinet.org/reports/sacanada.htm).