Statement by Dr. Adalbert Koestner, Chairman and Professor Emeritus, The Ohio State University

In a recent article entitled "Increasing Brain Tumor Rates: Is There a Link to Aspartame?" the authors (Olney, et al) consider aspartame to be a promising candidate for the increase in brain tumors. One of their major basis for this claim is their interpretation of the results of the rat carcinogenicity studies which were performed in the late seventies as a prerequisite for approval of aspartame for human consumption. The post-mortem examination of these animals following two years of aspartame feeding revealed a number of age-related lesions, among them a 2.8% brain tumor rate, as expected. The brain tumors were randomly distributed among the various groups of rats. (see Table I)

Table 1

Aspartame (2-years)

Brain Tumor Incidence

The authors claim that the most striking finding was that the aspartame-fed rats in study E33/34 had 12 malignant tumors and the control had no tumors. They ignored the one tumor in the control rat E33/34 and the 4 tumors in the control of E70. The tumors were mostly differentiated astrocytomas which bears no relationship to the human malignant glioblastoma referred to in the Olney article. They further claim that the tumors were of early onset, were rapidly growing, causing the animals to die at periodic intervals over the first and second year of the study. This was not the case.

In fact; 9 of 14 brain tumors referred to as gliomas were still microtumors at the termination of the experiment and were not detected grossly. They were only revealed because of the thorough examination of 8 sections from every brain. The survival of treated animals was comparable to that of controls, and no gliomas were confirmed as being the cause of death (Federal Register, Vol.48, No.142, 1981). A third claim was that the tumor incidence was dose-related with higher doses of aspartame being associated with higher tumor incidences. This is also a misrepresentation of facts. The table indicates that the tumors were randomly distributed. In study E-33/34 the highest incidence (5 tumors) was in a medium dose group while the highest dose group had fewer tumors (2 tumors) than the lowest dose group (3 tumors). In study E-70 the highest tumor rate (4 tumors) was in the control group; the highest dose group had only one tumor. There was no dose-effect relationship.

Results of the many subsequent carcinogenicity studies has improved our knowledge of spontaneous brain tumors. A 3% brain tumor rate in 2 year old Sprague Dawle rats is now widely recognized. One should not expect an equal distribution of these tumors among the various experimental groups. The distribution is entirely by chance. There is nothing in the distribution of brain tumors which would suggest an association between aspartame feeding and brain tumors. Further, there are valuable biological criteria available to distinguish between spontaneously developed brain tumors and those induced by neurocarcinogens. The latter show: 1. An increase of tumors beyond the expected spontaneous tumor level; 2. Shift of tumor appearance to younger age; 3. Dose-effect relationship; 4. Higher tumor incidence after transplacental exposure; 5. Trend toward anaplasia; 6. Presence of preneoplastic lesions; 7. Multiplicity of tumors in individual animals; 8. Genotoxicity, mutagenicity and chromosomal aberrations. These are the most important criteria. Aspartame fulfilled none of these criteria and can, therefore, not be considered to be a neurocarcinogen. The brain tumors in both studies are considered to be spontaneous. They would have occurred if nothing would have been done to these animals.

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