What are artificial sweeteners and how are they regulated in the United States?

Artificial sweeteners are regulated by the U.S. Food and Drug Administration (FDA). The FDA, like the National Cancer Institute (NCI), is an agency of the Department of Health and Human Services. The FDA regulates food, drugs , medical devices, cosmetics, biologics, tobacco products, and radiation -emitting products. The Food Additives Amendment to the Food, Drug, and Cosmetic Act, which was passed by Congress in 1958, requires the FDA to approve food additives, including artificial sweeteners, before they can be made available for sale in the United States. However, this legislation does not apply to products that are “generally recognized as safe.” Such products do not require FDA approval before being marketed.

Artificial sweeteners, also called sugar substitutes, are substances that are used instead of sucrose (table sugar) to sweeten foods and beverages. Because artificial sweeteners are many times sweeter than table sugar, much smaller amounts (200 to 20,000 times less) are needed to create the same level of sweetness.

What are artificial sweeteners and how are they regulated in the United States?

Questions about artificial sweeteners and cancer arose when early studies showed that cyclamate in combination with saccharin caused bladder cancer in laboratory animals. However, results from subsequent carcinogenicity studies (studies that examine whether a substance can cause cancer) of these sweeteners have not provided clear evidence of an association with cancer in humans. Similarly, studies of other FDA-approved sweeteners have not demonstrated clear evidence of an association with cancer in humans.

What have studies shown about a possible association between specific artificial sweeteners and cancer?

Saccharin

Studies in laboratory rats during the early 1970s linked saccharin with the development of bladder cancer, especially in male rats. However, mechanistic studies (studies that examine how a substance works in the body) have shown that these results apply only to rats. Human epidemiology studies (studies of patterns, causes, and control of diseases in groups of people) have shown no consistent evidence that saccharin is associated with bladder cancer incidence.

Because the bladder tumors seen in rats are due to a mechanism not relevant to humans and because there is no clear evidence that saccharin causes cancer in humans, saccharin was delisted in 2000 from the U.S. National Toxicology Program’s Report on Carcinogens, where it had been listed since 1981 as a substance reasonably anticipated to be a human carcinogen (a substance known to cause cancer). More information about the delisting of saccharin is available in the Report on Carcinogens, Fourteenth Edition.

Aspartame

Aspartame, distributed under several trade names (e.g., NutraSweet® and Equal®), was approved in 1981 by the FDA after numerous tests showed that it did not cause cancer or other adverse effects in laboratory animals.

A 2005 study raised the possibility that very high doses of aspartame might cause lymphoma and leukemia in rats (1). But after reviewing the study, FDA identified many shortcomings in it and did not alter its previous conclusion that aspartame is safe. In 2005, the National Toxicology Program reported that aspartame exposure did not cause tumors in or affect the survival of two types of genetically modified mice (2).

In 2006, NCI examined human data from the NIH-AARP Diet and Health Study of over half a million retirees. Increasing consumption of aspartame-containing beverages was not associated with the development of lymphoma, leukemia, or brain cancer (3).

A 2013 review of epidemiologic evidence also found no consistent association between the use of aspartame and cancer risk (4).

Sucralose

Sucralose, marketed under the trade name Splenda®, was approved by the FDA as a sweetening agent for specific food types in 1998, followed by approval as a general-purpose sweetener in 1999. Sucralose has been studied extensively, and the FDA reviewed more than 110 safety studies in support of its approval of the use of sucralose as a general-purpose sweetener for food.

In 2016, the same laboratory that conducted the aspartame studies discussed above reported an increased incidence of blood cell tumors in male mice fed high doses of sucralose (5). However, as with the aspartame studies, FDA has identified significant scientific shortcomings concerning the reported study results.

Acesulfame potassium, Neotame, and Advantame

Three other artificial sweeteners are currently permitted for use in food in the United States:

Acesulfame potassium (also known as ACK, Sweet One®, and Sunett®) was approved by the FDA in 1988 for use in specific food and beverage categories, and was later approved as a general-purpose sweetener (except in meat and poultry) in 2002.

Neotame, which is similar to aspartame, was approved by the FDA as a general-purpose sweetener (except in meat and poultry) in 2002.

Advantame , which is also similar to aspartame, was approved by the FDA as a general-purpose sweetener (except in meat and poultry) in 2014.

Before approving these sweeteners, the FDA reviewed numerous safety studies that were conducted on each sweetener, including studies to assess cancer risk. The results of these studies showed no evidence that these sweeteners cause cancer or pose any other threat to human health.

Cyclamate