Timeline of Selected FDA Activities and Significant Events Addressing Aspartame
The FDA first approved aspartame as a sweetener in 1974 and scientific evidence has continued to support the agency’s conclusion that aspartame is safe for the general population when made under good manufacturing practices and used under the approved conditions of use. The FDA-established acceptable daily intake (ADI), or the amount of aspartame that is considered safe to consume each day over the course of a person’s lifetime, continues to be protective of public health. However, people with difficulty metabolizing phenylalanine because of a rare genetic disorder called phenylketonuria (PKU) should avoid or restrict aspartame. Consumers can identify whether a product has aspartame by looking for it by name in the ingredient list on the product label, which must include a statement to inform people with PKU that the product contains phenylalanine.
The safety of a food additive must be supported by science that demonstrates its use meets the FDA’s safety standard. Aspartame is one of the most studied food additives in the human food supply. To determine the safety of aspartame, the FDA has reviewed more than 100 studies designed to identify possible toxic effects, including studies that assess effects on the reproductive and nervous systems, carcinogenicity, and metabolism. FDA scientists reassessed the science on the exposure and safety of aspartame in food each time the agency filed a food additive petition, received relevant information from other regulatory agencies and research institutions that have evaluated aspartame, and responded to objections that were raised related to the approved uses of aspartame. Since the last approved use in 1996, the FDA has continued monitoring the scientific literature for new information on aspartame. We stay abreast of published literature and the current level of consumer exposure and participate in international scientific and standard-setting activities related to food ingredient safety.
This timeline provides chronological information about FDA activities and significant events related to the review of aspartame.
1969
The FDA engaged with G.D. Searle & Co. (Searle) to discuss data needed for a food additive petition on aspartame. In 1969, Searle embarked on a safety testing program to collect data to submit a food additive petition on aspartame. The basic assumption made at the outset was that aspartame would be digested and metabolized like the amino acids and methyl esters present in foods. The tests conducted with laboratory animals and humans showed that the initial assumption was upheld; when aspartame-sweetened foods are consumed, the body treats the components of aspartame in the same way it treats amino acids and methyl esters in the foods eaten every day. Aspartame breaks down in the gut rapidly and completely to the amino acids aspartic acid and phenylalanine, which are absorbed and enter our body. Aspartic acid and phenylalanine are components of proteins and part of our diet.
February 1973
The FDA reviewed the first food additive petition, submitted by Searle, for the use of aspartame in foods. The FDA considered data and information such as the composition of aspartame, immediate and long-term health effects, and various safety factors in the agency’s evaluation of this food additive petition and determined if there was a reasonable certainty of no harm to consumers when aspartame was used as proposed.
July 1974
The FDA approved the use of aspartame as a tabletop sweetener and in chewing gum, cold breakfast cereals, and dry bases for certain foods (for example, beverages, instant coffee and tea, gelatins, puddings and fillings, and dairy products and toppings) and established a safe level of consumption from long-term toxicology studies.
August 1974
The FDA received objections on the July 1974 aspartame approval, and two objectors requested a hearing on aspartame's safety. Two objections were filed to the regulation in the 30-day comment period following the approval of aspartame. Among the topics included in the objections, were the incidence of brain tumors in aspartame feeding studies on rats and an uncontrolled pilot study on monkeys as the basis for their claim that phenylalanine in aspartame could lead to convulsions and mental retardation.
December 1974
The FDA proposes a Public Board of Inquiry (PBOI) to resolve questions raised by objectors. Though the FDA concluded in 1974 that the objectors had not presented evidence that aspartame is unsafe as regulated, the FDA was required to respond to a request for a hearing. The PBOI was recommended as a new procedure designed to provide a forum where scientists, without the legal formalities of an evidentiary hearing, can consider scientific issues and recommend regulatory action. The FDA later received agreement from the objectors to convene a PBOI in November 1975.
July 1975
The FDA Commissioner appointed a task force to investigate Searle's animal studies on seven products, including aspartame. This on-site investigation was to determine if Searle submitted false information to the FDA. An FDA task force was formed to examine Searle's animal studies that were submitted to support the safe use of six drugs and the food additive, aspartame. The FDA Commissioner testified before the U.S. Senate in July 1975 about the integrity of the data submitted to the FDA. FDA scientists conducted an on-site investigation between October 6, 1975, and December 19, 1975, and concluded that some of Searle's studies were questionable.
November 1975
The FDA received agreement from the objectors to the July 1974 aspartame approval regarding a Public Board of Inquiry (PBOI) to hear safety concerns.
December 1975
The FDA-appointed task force concluded that some of Searle's studies were questionable; therefore, the FDA stayed the aspartame regulation, and aspartame could not be marketed. Because of the problems noted in Searle’s studies, the FDA postponed the PBOI until questions raised by the FDA-appointed task force had been resolved. The PBOI was later convened in January 1980.
July 1976
The FDA decided to investigate the aspartame studies in response to the task force findings to determine whether the FDA could rely on these studies to assess the safety of aspartame. FDA scientists identified studies pivotal for determining the safety of aspartame and, in conjunction with the task force, selected 15 of 144 studies for audit. The FDA planned to audit three of the studies and worked with Searle to jointly select and negotiate a contract with Universities Associated for Research and Education in Pathology (UAREP), an independent audit team, to examine the remaining 12 studies.
April 1977
The FDA began investigating three aspartame studies. These studies were a tumorigenicity study in the rat on diketopiperazine (DKP), an evaluation of embryotoxic and teratogenic potential in the rat, and an evaluation of embryotoxic and teratogenic potential in the mouse. The FDA completed its validation of the three studies in July 1977.
August 1977
Per the FDA’s contract, UAREP began investigating 12 aspartame studies. UAREP validation of the 12 studies was submitted to the FDA in December 1978. UAREP reviewed the following studies: two-year rat study, lifetime rat study, two-year mouse study, long-term dog study, multi-generational rat study, supplemental dog analysis, supplemental rat analysis, mouse DKP study, rabbit teratology, newborn rat toxicity study, endocrine studies, and a pregnant monkey study. Upon completion of the UAREP report, FDA scientists evaluated the findings and concluded that the discrepancies did not compromise the data as submitted initially by Searle.
March 1979
The FDA concluded that the deficiencies found in both the agency’s and UAREP reviews did not invalidate Searle's aspartame studies. The FDA decided the PBOI could be convened, which happened in January 1980. The FDA concluded that the three studies they reviewed were authentic, and the conclusion from UAREP was that there were no discrepancies in any of the reports that were of sufficient magnitude or of a nature that would compromise the data initially submitted by Searle. Once the FDA and UAREP had completed the audit of the Searle data, the FDA selected the PBOI, composed of three university scientists.
January 1980
The FDA announced that the PBOI would begin. The FDA participated in the PBOI hearings on the objections to the 1974 aspartame approval. Some of the scientific issues raised at the PBOI were considered further through communications between the objectors and the FDA.
October 1980
The PBOI revoked the 1974 aspartame approval, concluding that more studies were needed to determine whether aspartame caused brain tumors. The FDA filed detailed exceptions to portions of the PBOI’s decision in which the PBOI disagreed with the agency’s position. Searle and another objector also filed detailed exceptions to portions of the PBOI’s decision.
March 1981
An FDA Commissioner's panel, consisting of FDA scientists and one lawyer, was established to advise the Commissioner on issues raised by the PBOI.
April 1981
The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established 40 mg/kg body weight as the acceptable daily intake (ADI) for aspartame. FDA experts routinely participate in JECFA, and the FDA had a participant in the 1981 JECFA.
July 1981
The FDA’s Commissioner overturned the PBOI decision and ultimately issued a decision to revoke the 1975 stay and allow the marketing of aspartame in dry foods. The Commissioner’s panel briefed the Commissioner on the issues concerning aspartame’s safety, and the Commissioner concluded there was reasonable certainty aspartame did not cause brain tumors. A novel feature of the Commissioner's decision was the incorporation of a condition that Searle provides the FDA with data on actual aspartame usage once products were on the market. This decision stated that while the available data establish that the maximum consumption was still far below any level even suspected of being toxic, these estimated use levels should be compared to actual use levels to ensure the validity of the safety assessment. Searle (and then NutraSweet) reported post-market survey data to the FDA through 2002.
July 1983
The FDA approved the use of aspartame in carbonated beverages. The FDA also established the ADI of 50 mg/kg body weight because of its review of the use of aspartame in carbonated beverages.
August 1983
The FDA received requests from objectors to stay the carbonated beverage regulation and hold a hearing on aspartame's safety. The FDA later denied these requests because the objections did not provide evidence that potential public harm may result from using aspartame in carbonated beverages. The FDA was named in a lawsuit in December 1983 filed by objectors (the Community Nutrition Institute (CNI)) in federal district court to require the FDA to hold a hearing and to stay both dry foods and beverages approvals. After the district court dismissed CNI's lawsuit, saying it lacked jurisdiction, the objectors petitioned in April 1984 for the U.S. Court of Appeals to review the dismissal and the FDA's denial of a hearing. Later, the Supreme Court declined to hear the case appealed by the objector.
May 1984
The FDA approved the use of aspartame in multivitamins.
July 1986
Objectors petitioned the FDA to repeal the dry foods and carbonated beverages regulations.
November 1986
The FDA denied the objectors’ petition to repeal the dry foods and carbonated beverages regulations. The FDA approved aspartame's use in fruit juices, stick-type confections, breath mints, and iced tea. The following month an objector petitioned the FDA to stay these regulations and requested a public hearing.
December 1986
The FDA declared aspartame safe as an inactive ingredient in drugs, provided the labeling meets certain specifications. The FDA approved the use of aspartame in ready-to-serve gelatin desserts.
January 1987
One objector petitioned the court of appeals to review the FDA's November 1986 denial of their petition.
June 1987
Government Accountability Office (GAO) concluded the FDA adequately followed its food additive approval process in approving aspartame for marketing by reviewing all of Searle’s aspartame studies, holding a PBOI to discuss safety issues surrounding aspartame’s approval, and forming a panel to advise the Commissioner on those issues.
January 1988
The Community Nutrition Institute (CNI) dropped its lawsuit to stay aspartame's clearance on dry foods and beverages approvals.
March 1988
The FDA published its response to the objections to the November 28, 1986, final rule for uses in fruit juices, stick-type confections, breath mints, and iced tea.
June 1988
The FDA issued six food additive final rules in response to six petitions requesting additional uses of the sweetener.
October 1988
The FDA published a final rule listing aspartame for use in the filling of prebaked cookies.
December 1988
The FDA published a final rule amending paragraph (b) of section 21 CFR 172.804.
June 1989
The FDA issued a final rule permitting the use of aspartame in frozen ready-to-thaw-and-eat cheesecake, fruit and fruit toppings; and frozen dairy and nondairy frostings, toppings, and fillings.
July 1989
The FDA received objections to the final rules published in June 1989 for the uses in frozen ready-to-thaw-and-eat cheesecake, fruit and fruit toppings, and frozen dairy and nondairy frostings, toppings, and fillings. The FDA later concluded that no new issues or reliable evidence had been presented to support the objections to the final rules. One of the objectors had not justified a hearing on its objections to the final rules. The FDA approved aspartame's use in fruit spreads, toppings, and syrups.
January 1992
The FDA approved aspartame for marketing in a bulk package, for hot and instant cereals, and for refrigerated and ready-to-serve puddings.
April 1993
The FDA approved aspartame for use in hard and soft candy, additional non-alcoholic beverages, and beer with less than three percent alcohol.
June 1996
The FDA approved the use of aspartame as a general-purpose sweetener in response to a petition from NutraSweet (formerly Searle). This approval simplified the existing regulation by replacing the 23 listed uses as a single category. The current regulation for the use of aspartame is found in title 21 of the Code of Federal Regulations.
December 2005
The European Ramazzini Foundation (ERF) presents new information to the public on aspartame, ERF’s first carcinogenicity study. The study was titled, “Long-term carcinogenicity bioassay to evaluate the potential biological effects, in particular carcinogenic, of aspartame administered in feed to Sprague-Dawley rats.” The FDA requested complete study reports, and ERF provided only some data.
May 2006
EFSA announced the results of their evaluation of the first ERF study and concluded there was no reason to revise the previously established Acceptable Daily Intake (ADI) for aspartame (40 mg/kg body weight).
2007
The FDA reviewed a number of additional aspartame studies, including the first ERF carcinogenicity study. The FDA concluded that none of these studies provided evidence to change the FDA's conclusion about the safety of aspartame. The FDA’s review included the following:
- A series of studies reported in 2005, conducted by the National Toxicology Program on the potential toxicity and carcinogenicity of aspartame in mice that were genetically modified to make them more susceptible to cancer,
- A large epidemiology study (>500,000 people) sponsored by the National Cancer Institute in 2006 that investigated whether there was any correlation between intake of aspartame and cancer,
- A two-year rat feeding study of aspartame and its decomposition product, 5-benzyl-3,6-dioxo-2-piperazine acetic acid, and
- A long-term carcinogenicity study of aspartame in rats that was conducted by ERF (the first ERF study).
The FDA requested data from a second carcinogenicity study in January 2007 published by ERF, but ERF declined to provide it.
March 2009
The EFSA Panel on Food Additives and Nutrient Sources added to Food published its opinion on the second ERF carcinogenicity study and stated there is no indication of any genotoxic or carcinogenic potential.
December 2013
The EFSA Panel on Food Additives and Nutrient Sources added to Food published its re-evaluation of aspartame and concludes aspartame is safe for the general population.
October 2014
The FDA denied two citizen petitions that asked the agency to revoke the authorizations for aspartame. The FDA concluded that the first citizen petition did not contain substantive scientific evidence demonstrating that aspartame’s use presents a public health risk or that this sweetener is adulterated or misbranded. The FDA concluded that the second citizen petition did not identify any scientific data or other information that would cause the agency to alter its conclusions about the safety of aspartame.
March 2021
The FDA reviewed a 2020 publication by Ramazzini Institute scientists titled “Identification of aspartame-induced haematopoietic and lymphoid tumours in rats after lifetime treatment”. The FDA concluded that it supports EFSA’s analysis that ‘no valid conclusion can be derived’ from ongoing analysis by the Ramazzini Institute of samples originating from Ramazzini Institute aspartame studies that have previously been deemed compromised.
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