Aspartame has been the predominant artificial sweetener in the U.S. for the past 25 years and is currently found in >6,000 food and beverage products (1). Throughout this period, however, there has been a controversy regarding whether or not aspartame is carcinogenic (2).
Speculation about an association between aspartame and brain cancer risk was raised in an article (3) which temporally linked increasing incidence rates in the U.S. during the period from 1975 to 1992, especially an upward shift of more aggressive glioblastomas during the 1980s, to the entry of aspartame in the food supply in 1981. The authors cited data from an earlier positive animal study reviewed by the Food and Drug Administration (4) and an in vitro nitrosation experiment (5) to support their hypothesis. The article was later criticized for committing ecological fallacy, wherein the temporal coincidence of two events observed at an ecological level without examination of individual data can lead to faulty conclusions regarding risk association (6), and the supporting evidence cited for the article was also refuted (7, 8). More recent and extensive animal trials have failed to show the carcinogenic activity of aspartame (1, 9-11). Additionally, a population-based case-control study found a null association between childhood brain tumors and aspartame intake among both children and their mothers during pregnancy and lactation (12). In contrast, however, a recent study found that female rats fed aspartame developed more lymphomas and leukemias than controls, in a dose-dependent manner, starting from a dose that may be relevant to human intake (as low as 20 mg per kg body weight;refs. 13, 14), which is lower than the acceptable daily intake established by the Food and Drug Administration at 50 mg per kg body weight (1). This study, compared with previous ones, had a large sample size (f1,800 rats) and was observed over a life span (13, 14).
Given the recent finding of an association between aspartame and hematopoietic cancers in rats, and past concerns about an association with brain cancers, we undertook a study to assess this relationship in a large prospective study of humans. We investigated the association between self-reported consumption of aspartame-containing beverages and incident hematopoietic and brain cancers in the prospective NIH-AARP Diet and Health Study.
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