National Toxicology Program

Q: What is Aspartame?

A: Aspartame was introduced in 1981 as a low-calorie sweetener under the brand names of NutraSweet® or Equal®. It is a nutritive sweetener made up of the amino acids aspartic acid and phenylalanine, as the methyl ester. It is considered a direct food additive by the Food & Drug Administration (FDA) and is used to sweeten beverages, puddings, yogurt, frozen desserts, breath mints, chewing gum, some vitamin and cold preparations and other foods. As a direct food additive, it is normally identified on the ingredient label.

Q. Why was it studied?

A: Although FDA determined in 1981 that aspartame was safe for use in foods, that agency has continued to review complaints alleging adverse reactions to products containing aspartame. FDA has not determined any consistent pattern of symptoms that can be attributed to the use of aspartame, nor is the agency aware of any recent studies that clearly show safety problems except in certain people with the genetic disease phenylketonuria (PKU). Even though aspartame has been evaluated in conventional rodent cancer studies (non NTP studies) and is considered negative, it has been argued that the studies showed a slight increase in brain tumors. Because of this uncertainty, the National Toxicology Program¹ was interested in evaluating the toxicologic potential, including possible carcinogenicity, of aspartame.

The National Toxicology Program (NTP) studied aspartame in three transgenic or genetically manipulated mouse strains, Tg.AC, and, p53, and, p16. The NTP included studies in the p16 mouse because this model is proposed to be susceptible to glial cell tumors of the brain. The aspartame study protocol (pdf document -- get free reader from Adobe) provides information about the conduct of these studies. Learn more about the selection of the mouse strains used in these studies: NTP Evaluation of Genetically Manipulated Mice as Adjunct Models in Toxicity/ Carcinogenicity Assessment.

Q. What information is available from these studies on aspartame?

A. Studies on aspartame are now complete and the following study results are posted on the NTP website (http://ntp.niehs.nih.gov/ntpweb/index.cfm?objectid=47627573-F1F6-975E-762AC3A1EA057957).

The NTP designed and conducted studies on aspartame to characterize and evaluate its toxicologic potential, including possible carcinogenic activity. Data for the completed studies of aspartame are presented 3 mouse strains and include links for data and statistical analyses for the following endpoints: 1) occurrence or tumors (neoplasms), 2) non-neoplastic lesions or abnormal cell growth, 3) body weight, and 4) survival.

Prior to finalizing pathology data, it was peer reviewed by an external pathology working group (PWG) that conducted quality assurance examination of the data and resolveed any differences between results reported by the study laboratory and assessments by the NTP staff. In addition, all study data were subjected to an NTP retrospective audit and the interpretation modified based on these findings. It should be noted that in determining its final conclusions about the toxicity or carcinogenicity of an agent, the NTP assessed a broad array of information that took into account all data obtained from the NTP studies, data from controls included in previous NTP studies (historical controls), plus data from relevant published literature.

¹ See the 2002 NTP Current Directions and Evolving Strategies