. The Truth About Aspartame Low Calorie Sweetener
The Truth About Aspartame Aspartame and Nutrition Facts
What is Aspartame
Aspartame in the Diet
Safety of Aspartame
Aspartame Use by Special Groups
Aspartame proven safe in more than 200 studies Aspartame approved for use in more than 100 countries

Aspartame Safety Scientific Review

Overview of Safety and Regulatory Status

Aspartame is one of the most thoroughly tested ingredients in history.  Prior to the approval of aspartame, a comprehensive battery of studies was done in humans and animals, including toxicity and carcinogenicity studies in several animal species.  The results of these studies demonstrated that aspartame, even in amounts many times that possible from human consumption, is safe as part of a daily diet (Butchko et al, 2002).

The studies done with aspartame have been reviewed by regulatory scientists around the world, including the US Food and Drug Administration  (FDA, 1981), the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1980), and the Scientific Committee on Food of the European Union in 1985 (SCF, 1985) and again in 2002.  In each case aspartame was determined to be safe for human consumption.  At the time of approval in the US, the FDA Commissioner stated, “Few compounds have withstood such detailed testing and repeated, close scrutiny, and the process through which aspartame has gone should provide the public with additional confidence of its safety” (FDA, 1981).  After its comprehensive 2002 review, the SCF reconfirmed aspartame’s safety.  "The Committee concluded that on the basis of its review of all the data in animals and humans available to date, there is no evidence to suggest that there is a need to revise the outcome…” of that authority’s prior endorsement of aspartame's safety  (SCF, 2002).

Available for 25 years, aspartame is now approved for use by the general population in more than 100 countries around the world.  The only exception is individuals being treated for the rare genetic disease, phenylketonuria (PKU), who must carefully monitor phenylalanine intake from all dietary sources, including aspartame.

Anecdotal questions regarding the safety of aspartame raised since its approval have been extensively evaluated by medical postmarketing surveillance and by the conduct of numerous additional animal and human studies (Tschanz et al, 1996).  The results of these studies confirmed the safety conclusions of the earlier studies.  Thus, the animal and human studies done with aspartame have clearly established that it is a remarkably safe food additive.

Aspartame Structure and Metabolism

Aspartame is a very simple compound and is broken down in the GI tract into three components:  the amino acids, aspartic acid (40% by weight) and phenylalanine (50% by weight), and methanol (10% by weight) (Oppermann et al, 1973; Ranney et al, 1976; Ranney and Oppermann, 1979; Karim and Burns, 1996).  These components are then absorbed and utilized by the body via the same metabolic pathways as when they are derived from common foods.  In fact, these same components are consumed in much greater amounts from everyday foods, such as eggs, milk, meat, fish, cheese, fruits and vegetables (see below). Thus, based on its metabolism to small amounts of common dietary components, it is not surprising that aspartame is safe and has no adverse health effects (Butchko et al, 2002). 

Although some have attempted to raise alarm about methanol as a breakdown product of aspartame, the safety of methanol and methanol derived from aspartame has been extensively evaluated.  In fact, based on food safety estimates by the FDA, an individual could consume about 30 liters of 100% aspartame-sweetened beverage per hour around the clock (which is impossible) without adverse effects from methanol. 

The methanol produced during the digestion of aspartame is identical to that which is provided in much larger amounts from many fruits, vegetables and their juices and is part of the normal diet.  Regardless of the source, after methanol is formed it is further broken down through normal body processes.

Approximate Amino Acid Content of Various Foods

 

Aspartic acid (mg)

Phenylalanine (mg)

Aspartame-sweetened soft drink (12 ounces)

72

90

Skim milk (12 ounces)

948

598

Chicken (approx 4 oz.)

2570

1130

 

Approximate Methanol Derived from Various Beverages (mg/12 ounces)

Aspartame-sweetened soft drink

 

Orange juice

 

Apple juice

 

Red grape juice

 

Tomato juice

18

23

29

65

107

Aspartame Carcinogenicity Studies

Four carcinogenicity studies (twice the required number) were done with aspartame during the regulatory review and approval process, three in rats (including in-utero exposure) and one in mice.

The conclusion of all four studies, using doses of aspartame hundreds of times higher than the 90th percentile intake by humans, is that aspartame is not carcinogenic (Butchko et al, 2002), including no increases in brain tumors, tumors originating from any neurological tissue, urinary tract tumors, lymphomas, or leukemias. Based on detailed reviews and evaluations of the data from the aspartame carcinogenicity studies, regulatory agencies, including the FDA and Health Canada, and expert committees, including JECFA and SCF, all concluded that aspartame is not a carcinogen.

The studies with aspartame used protocols that were the standard for the time – essentially the same as standard protocols for carcinogenicity studies used today (e.g., 104-week duration).  Results of the studies submitted for regulatory approval – involving a total of 1080 animals and 28,000 tissue sections – were validated by the Universities Associated for Research and Education in Pathology, Inc. (UAREP) through an exhaustive audit and re-analysis at the request of FDA, further reinforcing confidence in the aspartame review and its conclusions. (UAREP, 1978; FDA, 1981, E-33/E/34, E-70 and E-75).

When questions about aspartame and brain tumors arose in the middle 1990s based on misinterpretation of cancer incidence data in the US (Olney, 1996), several experts (Levy, 1996; Flamm, 1997; Koestner, 1997) and regulatory and government agencies (FDA, 1996b; NCI, 1997; ANZFA, 1997; United Kingdom Department of Health, 1998, Food Standards Agency, 1999; European Commission, 1997) reviewed the facts and again concluded that aspartame is not associated with brain tumors. 

In 2003, the U.S. National Toxicology Program (NTP) completed three carcinogenicity studies in which aspartame was fed to groups of male and female transgenic (cancer models) mice for a period of 40 weeks at levels of up to 5% of the diet equivalent to about 2500 times that of those who consume the very highest levels of aspartame (90th percentile) in the U.S.  Again, these studies, sponsored by the U.S. government and conducted under accepted laboratory procedures found that  “aspartame did not cause cancer in the genetically modified mice used in these studies” (NTP, 2005).

In addition to the carcinogenicity studies in animals, an epidemiology study from the US National Cancer Institute, also found no cancer incidence linked to aspartame consumption.  The study evaluated over 500,000 men and women and found (compared with those who did not consume aspartame) that there was no evidence of an increased risk of leukemias, lymphomas and brain tumors among those who used aspartame.  (Lim et al, 2006).

More recently, an additional study published by Italian and French researchers found no association between aspartame and cancer in humans (Gallus et al, 2007).  The researchers evaluated a variety of studies, published between 1991 and 2004 in over 7,000 men and women.  The researchers noted, “In conclusion, therefore, this study provides no evidence that saccharin or other sweeteners (mainly aspartame) increase the risk of cancer at several common sites in humans.”  The Italian Association for Cancer Research contributed to the study. 

Recent Allegations by Soffritti et al (of the Ramazzini Institute) Flawed 

A 2005 study by Soffritti et al alleges that aspartame induces leukemias and lymphomas and other tumors based on a rat study conducted at the Ramazzini Institute in Italy.  This work was printed in a publication (European Journal of Oncology) owned by the Institute itself, and posted on the Institute’s Web site in June 2005.  The authors have also made presentations and statements to media.  The study was posted online in November 2005 and published in March 2006 in Environmental Health Perspectives, a publication ofthe National Institute of Environmental and Health Sciences (NIEHS). 

The design and execution of the Soffritti study did not follow guidelines set up by the National Toxicology Program (NTP), the U.S. government toxicology initiative administered by the National Institute of Environmental and Health Sciences (NIEHS).  In October 2005, NIEHS informed the Calorie Control Council, “The NTP has convened a group of pathologists to review selected histopathological lesions from the RF [Ramazzini Foundation] aspartame cancer bioassays.  The NIEHS has not carried out a systematic pathology review of the RF aspartame studies.”  NIEHS has confirmed that it had no role in the design, performance or interpretation of the Ramazzini study and stated it is not putting NIEHS’ reputation behind this study. 

The Soffritti et al findings were reviewed in July 2005 by the expert UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment. Members of that Committee characterized aspects of study findings as “implausible,” with other aspects “cast(ing) doubt” on the entire study.  The members of the Committee were “critical” of the study design and the statistical approach used.  Following a more in-depth review, the expert UK Committee noted, “Overall, members concluded that, in view of the problems in the design of the study and some concerns about the microbiological status of the colony, it was not possible to draw conclusions about the potential carcinogenicity of aspartame from the results.”   

In May 2006, the European Food Safety Authority issued its report of a comprehensive evaluation of the Ramazzini aspartame study and noted, “After its evaluation the Panel considers that the study has flaws which bring into question the validity of the findings, as interpreted by the ERF [European Ramazzini Foundation].  In particular, the high background incidence of chronic inflammatory changes in the lungs and other vital organs and tissues and the uncertainty about the correctness of the diagnoses of some tumour types were major confounding factors in the interpretation of the findings of the study.”

Review of the Soffritti et al paper, as well as its authors’ allegations and preliminary statements, raise numerous issues and questions, some of which are highlighted below:

  • The conclusions are in direct conflict with US and European cancer incidence data since aspartame’s approval and widespread use.  An evaluation of data from the US National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program, commissioned by the Calorie Control Council, found no associations between cancer epidemiological data and aspartame’s approval. Overall aspartame consumption increased dramatically from 1980 to 1995, with a more modest increase between 1995 and 2002.  Cancer incidence rates for Hodgkin’s lymphoma and leukemia have not increased and actually decreased slightly from 1973-2002.  The incidence of Non-Hodgkin’s lymphoma (NHL) increased from 1973-2002, in part due to the rise in HIV/AIDS infection, but leveled off from the mid-1990s to 2002.  Further, no pattern that paralleled the rise in aspartame consumption was found by gender or age group. Similarly, mortality trend data from the European Union for leukemias and Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma are not consistent with any carcinogenic effect of aspartame.
  • There is no indication of an association between aspartame consumption and any cancer in humans based on extensive postmarketing surveillance data since its approval and widespread use (Tollefson, 1988; CDC 1984). 
  • The findings are at complete odds with the four previously conducted carcinogenicity assessments, as well as the recent assessment carried out by the National Toxicology Program and the extensive data base of other studies confirming aspartame safety.
  • The methodology did not follow the internationally established protocols for animal carcinogenicity studies.* All recommend carcinogenicity studies of 104 weeks duration using 50 animals per sex per group. Soffritti et al used the abandoned practice of allowing the study to go until all rats died spontaneously, considered unacceptable by most cancer researchers because of the misleading information that such practices yield.  Rats, like people, develop a range of cancers in old age.  Thus, establishing whether there is a cause and effect of tumors or cancer associated with treatment in rats that have died of old age is not possible. 
  • Tumor results were inappropriately combined for analysis.  Soffritti et al combined the incidence of many cancer cell types in their analysis – the equivalent of “mixing apples and oranges” in scientific research and raising serious questions about the statistical validity of the conclusions.  In addition, information on tumors per animal is not provided – only total number of tumors per group – again making clear evaluation impossible.
  • Neither dose response data nor survival data are consistent with carcinogenic effect.  The historical control tumor rate stated by authors in female rats is essentially the same as that observed up through the 10,000 parts per million level of aspartame in the diet.
  • NIEHS informed the Calorie Control Council, “The NTP has convened a group of pathologists to review selected histopathological lesions from the RF [Ramazzini Foundation] aspartame cancer bioassays.  The NIEHS has not carried out a systematic pathology review of the RF aspartame studies.”  The study was published in NIEHS’ journal Environmental Health Perspectives (EHP).  However, it is difficult to understand why the agency would publish such a study when the design and execution of the study did not follow guidelines set up by the National Toxicology Program (NTP), the U.S. government toxicology initiative administered by the NIEHS. 

The study is also available on the Ramazzini Institute’s Web site at http://www.ramazzini.it/fondazione/docs/AspartameGEO2005.pdf  and published in the Ramazzini Institute’s own journal, the European Journal of Oncology.  The European Journal of Oncology is not included in the MedLine (National Library of Medicine) database – the world’s leading source of scientific literature.  In order for a journal to be included in MedLine, it must meet the following criteria:  The journal should demonstrate features that contribute to the objectivity, credibility, and quality of its contents.  These features may include information about the methods of selecting articles, especially on the explicit process of external peer review; statements indicating adherence to ethical guidelines; evidence that authors have disclosed financial conflicts of interest; timely correction of errata; explicit responsible retractions as appropriate; and opportunity for comments and dissenting opinion.”  Clearly, publication of a study conducted by a senior member of the Ramazzini Institute in its own journal cannot be considered to have received a thorough and unbiased review prior to publication.

Conclusion

Aspartame is a common ingredient in the global food supply that has been consumed by hundreds of millions of people for more than 20 years.  No association with any disease, including cancer, has ever been detected.  To the contrary, it is widely accepted as a valuable tool that is extremely useful in helping the large numbers of individuals attempting either to manage body weight or combat obesity – a proven risk factor for numerous cancers.  Attempts to shift public attention in ways that deflect focus from real cancer risks are unwarranted and irresponsible.

04/07

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* A scientific consensus was established in the 1970s and was formalized in a 1982 United States Food and Drug Administration publication, “Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food” (also known as “The Redbook”), the Organisation for Economic Co-operation and Development’s “2000 Guidelines for the Testing of Chemicals” (including previous versions), and the European Union’s Scientific Committee on Food in its 2001 “Guidance on Submissions for Food Additive Evaluations” (including previous versions).

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