The Journal of Advancement in Medicine
Volume 4, Number 4, Winter 1991

H. J. Roberts, MD (H.J. Roberts MD is Director, Palm Beach Institute for Medical Research. He is Senior Active Staff, St. Mary’s Hospital and Good Samaritan Hospital, West Palm Beach. He is author of six texts and was selected the “The Best Doctors in the U.S.” Addresss correspondence to H. J. Roberts MD, Palm Beach Institute for Medical Research, 300 27th Street, West Palm Beach, FL 33407.

1991 Human Sciences Press, Inc.

ABSTRACT:  There has been a statistically significant increase of common primary malignant brain cancers since 1985, and perhaps as early as 1984, according to the National Cancer Institute SEER data. This phenomenon occurred within 1-2 years following licensing of the chemical aspartame for beverages in July 1983. Furthermore, the annual incidence rates of primary brain tumors appear to be increasing.  The SEER data also reveal an increased incidence of primary brain lymphoma in 1982-1984. Others have reported a tripling of the incidence of this condition, previously rare.  Again, the licensing of aspartame for “dry” use in July 1981 is relevant.  The significance of these associations is underscored by the high incidence of brain tumors in rats after the experimental administration of aspartame. Food and Drug Administration (FDA) scientists and a Public Board of Inquiry (PBOI) strongly recommended delay in licensure pending further investigation, including repetition of the animal studies, to clarify this matter. To the author’s knowledge, these have not been reported. Aspartame containing products are now being consumed by an estimated 200 million persons in over 4,000 products. These data, coupled with an unacceptably large number of aspartame-related seizures reported to the FDA and the writer, appear to warrant an “imminent public health hazard” designation for such products.

Introduction
The title of this article should disturb seasoned clinicians. It suggests that several major human cancers may be caused or influenced by an additive currently being consumed by more than half the population.

Such an assertion obviously requires epidemiologic and statistical validation, as well as the repetition by corporate-neutral investigators of animal and human studies on which the FDA had relied for licensing products containing this synthesized chemical.

The Rising Incidence of Primary Brain Cancer
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) statistics (1) indicate an impressive increase in the age-adjusted incidence rates of primary brain cancer since 1985, and possibly as early as 1984. This phenomenon has been documented in the categories covering all races and both genders.

Disturbing statistically-significant rises in the Estimated Annual Percent Change (EAPC) for brain cancer also were noted in the 1983-1987 period - 1987 being the last year for which complete data are available. For example, SEER Table II-34 contains the five-year trends for all races. The EAPC rose from 2.1 to 8.7 in males, and from 2.1 to 11.7 in females for the time periods 1975-1979 and 1983-1987, respectively.

Although such increases might be attributed to more accurate diagnosis by modern scanning and other diagnostic procedures, three considerations seem to rebut this explanation. First, adequate brain scanning devices were widely available at least one decade ago. Second, the rise in primary brain tumors has been quantitative, and not attributable to changes in nosology. Third, the incidence rates for cancer involving most other systems either remained stable or declined during the 1983-1987 period.

The search for nonoccupational etiologic factors of glioblastoma in adults has proved frustrating (2). Hochberg, Toniolo and Cole (3) were unable to document any significant association with a family history of central nervous system (CNS) malignancies or other neurologic conditions. Exposure to pets, a farm environment, head irradiation, cigarette smoking, alcohol consumption, the intake of cured or smoked meat or fish, or the use of various drugs did not appear to correlate.

The Rising Incidence of Primary Brain Lymphoma
The increasing frequency of primary brain lymphoma of B cell derivation - including reticulum cell sarcoma, microglioma and histiocytic lymphoma - also requires explanation because this subset was previously rare.

Eby et al (4) reported a nearly threefold rise in its incidence among immunologically normal persons in the 1982-1984 SEER data, which they could not explain. Specifically, the rate increased from 2.7 to 7.5 cases per ten million population (p=0.001) in the time periods 1973-1975 and 1982-1984, respectively. The age-adjusted rise was more striking among women which increased from 4.9 per ten million in 1979-1981 to 8.9 per ten million in 1982-1984.

Hochberg and Miller (5) reported a tripling of incidence of this tumor in non-immunosuppressed persons  during the 5-year interval between 1980 and 1984. Moreover, there was a decrease in the median age of onset by 3.5 years. They projected that the tumor could be the most common neurological neoplasm by 1991 because of its increase both sporadically and in the acquired immunodeficiency syndrome (AIDS) population.

Hardwidge et al (6) noted the increased incidence of primary cerebral lymphoma encountered since 1987 in their neuropathology center in England.   They suggested the importance of epidemiological studies to determine any environmental factors that might be implicated.

This phenomenon coincides with two other events: (a) the formal licensing of aspartame in July 1981, and (b) the 3:1 preponderance of women with adverse reactions to aspartame products (7,8). Eby et al (4) suggested other noninfectious environmental exposures as a possible explanation. Although primary brain lymphomas might have a long latency period and result from occupational exposure or other chemical exposures, these investigators regarded occupational exposure to be an unlikely cause in view of the similar increases in incidence among both men and women, particularly in older persons.

Aspartame Consumption
Any attempt to explain this increase in incidence of primary brain cancers must seriously consider the widespread consumption of aspartame products. Aspartame (NutraSweet) was licensed for use as an additive in the Generally Regarded as Safe (GRAS) category by the Federal Drug Administration (FDA), first as a tabletop sweetener in July 1981, and then for “wet” use in beverages in July 1983. Long-term clinical studies in humans were not reported, to our knowledge, before such licensure. Currently, more than 4,000 products containing aspartame are being consumed by over 200 million persons, often in prodigious amounts (7).

Experimental Aspartame-Associated Brain Tumors
An unexpectedly high incidence of primary brain tumors was found in rats experimentally exposed to aspartame during the 1970s (7). Although FDA scientists and others expressed considerable concern, the statutes of limitation on such studies were allowed to expire before regulatory action could be taken. The details were published in the Congressional Record-Senate hearings of May 7 (9) and August 1, 1985 (10), and in a recent text (7).

Park, a Staff Science Advisor for the Office of Health Affairs of the Department of Health and Human Services, concluded an analysis of aspartame safety by a special PBOI relative to brain tumors in aspartame-treated rats (11). He stated that aspartame had not been shown to be safe for the proposed food additive uses.  The PBOI accordingly recommended that aspartame should not be approved until additional studies were performed using proper experimental designs.

These studies were never reported, to our knowledge, even though producers of aspartame continue to tout it as “the most thoroughly tested additive in history”. If mutagenic, it could be due to the molecule itself, one or more of its three components (phenylalanine, aspartic acid, methyl alcohol), or their breakdown products. The latter include steroisomers of the amino acids and/or multiple metabolites, especially the diketopiperazine derivative (DKP). It is noteworthy that these breakdown products increase during the prolonged storage and exposure to heat to which many aspartame products are exposed (7).

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