Provided by the Food and Drug Administration Via E-Mail January 27, 1999

The Food and Drug Administration's Center for Food Safety and Applied Nutrition has recently received numerous requests for information and evaluation regarding an article attributed to a Ms. Nancy Markle. In that article Ms. Markle claims that ingestion of the artificial sweetener, aspartame, results in the occurrence of a number of toxicities. The review of the safety of aspartame presented below is being circulated to provide a more accurate and complete assessment of the data/findings, both from animal and clinical studies, that are currently available on aspartame.

This review is compiled by the scientists that have worked on questions relating to the safety of aspartame repeatedly since 1978. These scientists are familiar with the scientific studies that have been conducted to support the safety of this food additive. There were well over 100 separate toxicological and clinical studies conducted to establish the safety of aspartame before it was approved for regulatory acceptance. Since its approval in 1981 by the USFDA, there have been many additional studies performed to follow up on some of the more credible reports of aspartame-mediated adverse effects. Below agency scientists have tried to succintly respond to certain of the allegations of toxicity proposed by Nancy Markle.

First, reports of the ingestion of aspartame in patients who later have suffered multiple sclerosis or systemic lupus is obviously not scientifically sustainable evidence that aspartame is responsible for the occurrence of either disease. Both of these disorders are subject to spontaneous remissions and exacerbations so it is entirely possible that when patients stopped using aspartame they might have also coincidentally have had remission of their symptoms. Alternatively, the worsening of disease symptoms could be temporally correlated with the start of aspartame use. The most important consideration, however, is that there is no credible evidence that the FDA is aware of that suggests that aspartame elicits multiple sclerosis or systemic lupus.

Second, the claim that aspartame ingestion results in the production of methanol, formaldehyde and formate. These claims are factual. In the gastrointestinal tract aspartame is hydrolyzed to one of its component materials, methanol, as well as the two amino acids, phenylalanine and aspartic acid. This methanol is taken up by the cells of the body and metabolized first to formaldhyde and then to formate. The key information that is missing in the description by Ms. Markle is that the levels of ingestion are very modest. In fact, there are other foodstuffs that we ingest that supply as much and sometimes even more methanol; e.g., citrus fruits and juices, and tomatoes or tomato juice. There are even higher quantities of methanol ingested when ethanol is consumed. Thus, in the final analysis this methanol is the same as from other sources of food and in the quantities consumed from aspartame, it is readily and naturally metabolized via the one-carbon biochemical cycle to entirely innocuous and natural body components.

Third, the claim that the two amino acids, phenylalanine and aspartic acid have neurotoxic effects. This is true in certain individuals and in high enough doses. The only subpopulation of individuals potentially susceptible to adverse effects from phenylalanine is homozygous phenylketonurics and in this case, food itself with much higher levels of phenylalanine from the protein in the diet contributes much higher toxicity for these unfortunate individuals. For those individual phenylketonurics who want to carefully control their intake levels of phenylalanine, they can do that by simply taking into consideration the amount of phenylalanine supplied by the aspartame product or, even more likely, simply refraining from use of these products. The USFDA requires that the aspartame product be labeled specially for phenylketonuric patients so that they will be aware of its presence in these products. As for the other amino acid in aspartame, the levels of aspartic acid ingested with aspartame use are many fold less than those levels responsible for causing adverse effects on the brain of animals and/or man. In fact, it is not clear that the experimentally derived data from animals is relevant to man. In any case, the levels of aspartic acid intake from aspartame are many fold below those needed to mediate neurotoxic effects.

Fourth, there have been numerous animal and human studies done to evaluate the possibility that aspartame causes seizures or enhances the susceptibility to seizures. In clinical studies done in adults and children with preexisting seizures, there was no evidence of contributing to the frequency of occurrence or severity of seizures in seizure-prone individuals. There were additional studies done on seizure-prone experimental animal models to assess the possible influence of aspartame on their seizuring activity. Again, the result was the same and no influence was demonstrated on the frequency or severity of seizures.

Fifth, aspartame was comprehensively evaluated for its potential to mediate adverse reactions on the ability of pilots to fly planes. There were a number of individual complaints registered with the FDA claiming that ingestion of aspartame resulted in an interference with individuals' ability to fly planes. For example, dizziness, impairment of vision and mental acuity were reported. The FDA took these reports seriously and instituted a contract to perform a study to see if these effects could, in deed, be reproduced. FDA contracted with the Federal Aviation Agency who subcontracted studies with psychophysiological testing laboratories to determine whether aspartame could affect mental functioning, and manual dexterity. The overall outcome of the studies was that there was no difference between placebo (control) treatment and exposure to aspartame although a positive control group receiving ethanol did show impairment of manual dexterity and ability to deal with complex information.

Sixth, recently Dr. John Olney of Washington University in St. Louis, Missouri claimed that data collected by the National Cancer Institute demonstrated an increase in the incidence of brain tumors in human patients since aspartame was approved for use in the US food supply. A number of scientists both in government and in academic settings have carefully evaluated Dr. Olney's claim and have refuted it. There has been an increase in the number of brain tumors reported during recent years, but the explanation for this increase is most likely to be the technological enhancements of tumor diagnosis (e.g., computerized tomography and magnetic resonance imaging) introduced during this same time that has enabled greater sensitivity and certainty in the diagnosis of tumors. In the more recent data on tumor occurrence in the US, there is a plateauing or even a slight diminution of brain tumor incidence and this in the face of the continued presence and use of aspartame in many food products.

Seventh, aspartame was subjected to several specially designed animal tests to assess its potential to adversely influence reproduction and to mediate birth defects. All of the well-designed and conducted tests demonstrated that aspartame was safe and did not produce birth defects or adverse responses on reproductive function.

In conclusion, as mentioned earlier, aspartame is one of the most thoroughly tested food additives ever submitted to the FDA. All of the early testing in animals and human subjects conducted to support the safety of aspartame as well as the well-designed and conducted studies subsequently performed to assess whether aspartame might mediate a number of anecdotally reported symptoms have reinforced the appropriateness of FDA's approval and regulation of aspartame as a safe food additive.


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