Such exceedances are especially common among infants and young children because of their greater food intake per Kg body weight compared to adults and their unusual dietary patterns [ 11 ]. The implication of this finding is that current ADI levels for aspartame may be set too high and may not offer sufficient protection against cancer.
ADI levels for aspartame need urgently to be reevaluated, especially as they apply to pregnant women and young children. The RI reanalysis [ 22 ] documents the power of new technologies such as immunohistochemical analysis [ 14 , 20 ] and harmonized diagnostic classification, such as the INHAND classification [ 21 ], to resolve diagnostic controversy. These state-of-the-art techniques improve accuracy of diagnoses of lymphoma and leukemia in rats.
Going forward, standardized techniques such as these should routinely be incorporated into all toxicity assays, just as standard diagnostic criteria are now used for classification of hematolymphatic malignancies in humans [ 23 ]. The finding that prenatal exposure to aspartame increases incidence of leukemia and lymphoma in offspring in rodents is of grave concern Fig. Pregnant women and young children consume large quantities of foods and beverages sweetened with aspartame [ 24 ].
In the United States, pregnant women extensively consume aspartame-containing soft drinks to prevent weight gain during pregnancy.
Fetal aspartame exposure is the inevitable consequence. These findings raise the possibility that aspartame may be a contributor to current increases in incidence of leukemia and other cancers in children [ 25 ]. National and international public health agencies need to take careful notice of these revalidated findings. Previous facile dismissals of the carcinogenicity of aspartame can no longer be sustained [ 8 , 9 , 17 , 18 ].
Long experience documents that delay in acting on well-documented evidence of chemical carcinogenesis results in unnecessary disease and preventable death [ 26 — 28 ]. The findings presented here underscore the need for epidemiologic studies of cancer incidence in populations exposed to aspartame — especially children exposed to aspartame in utero. To date, only two epidemiologic studies have been conducted of aspartame-exposed populations. The first, a study conducted in a very large population of middle aged Americans by the US National Cancer Institute, showed no carcinogenic effect [ 29 ].
Although the population was large, this study used a relatively weak questionnaire instrument for assessing aspartame exposures and appears to have been subject to exposure misclassification. Moreover, reported exposures were generally low and the study was not designbed to assess the consequences of aspartame exposures in early life.
A second epidemiological study conducted within the prospectively followed population of the Harvard Nurses Health Study carefully assessed exposures and reported a significantly elevated risk of non-Hodgkin lymphoma NHL in males who consumed one or more servings of soda per day [ 30 ].
There reappeared to be a positive exposure-response relationship between soda consumption and NHL risk. Additional, carefully conducted epidemiological studies of the potential of aspartame to cause cancer in humans are very much needed, with a particular focus on early-life exposures.
This call reiterates a plea for such reexamination that was made by Ramazzini Institute scientists in [ 31 ]. We call upon food agencies in countries around the world to reassess Acceptable Daily Intake ADI levels for aspartame.
Both authors provided equal writing and editing to the original and subsequent drafts. All authors approved the final version of the manuscript. There is no financial conflict of interest. Both Dr. Landrigan and Dr.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Philip J. Landrigan, Email: ude. Kurt Straif, Email: ude. National Center for Biotechnology Information , U. Journal List Environ Health v. Environ Health. Published online Apr Landrigan 1, 2, 3 and Kurt Straif 4, 5.
Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received Feb 2; Accepted Apr 6. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.
If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Aspartame and cancer — new evidence causation " in volume 20, This article has been cited by other articles in PMC. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents.
Introduction For decades, controversy has surrounded the question of whether the artificial sweetener, aspartame can cause cancer. The Ramazzini Institute studies of aspartame In , in response to rising concerns about the safety of aspartame, the Ramazzini Institute RI , an independent, not-for-profit research laboratory in Bologna, Italy initiated a series of large-scale toxicological studies of the possible carcinogenicity of aspartame. Open in a separate window.
The controversy Publication of the RI findings on the carcinogenicity of aspartame generated intense controversy [ 15 ].
Methods Resolution of the controversy To address these issues, RI reexamined all lesions in Sprague-Dawley rats that had been diagnosed as hematopoietic and lymphoid tissue tumors HLTs in the experimental study that initiated aspartame dosing prenatally BT Two state-of-the-art diagnostic techniques were employed: Immunohistochemical analyses. Results Immunohistochemical analysis and morphological reclassification of all lesions originally diagnosed as hematopoietic and lymphoid tissue tumors HLTs have now been completed [ 22 ].
Implications for public health and Cancer prevention The state-of-the-art reanalysis of the Ramazzini Institute data [ 22 ] confirms that aspartame is a chemical carcinogen in rodents. Current use levels of aspartame, even by high users in special subgroups, remains well below the U. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels.
Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior.
Searches across all databases were conducted from the earliest available date up to April 13, , without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively.
Twenty-nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Aspartame consumption was not associated with alterations on blood glucose levels compared to control Total cholesterol was not affected by aspartame consumption compared to control
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