Abstract

BackgroundAspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women.The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults.These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms.MethodsTo address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria.FindingsThis immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection.InterpretationThese new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies.These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.

Highlights

  • Controversy has surrounded the question of whether the artificial sweetener, aspartame can cause cancer.Aspartame was first manufactured in 1965

  • A important use in the United States is in the manufacture of lowcalorie beverages that are extensively consumed by children and pregnant women [3]

  • The morphological features of all lesions that had originally been diagnosed as lymphoma or leukemia were reexamined and reclassified according to the most recently updated Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria - the Internationally Harmonized Nomenclature And Diagnostic (INHAND) criteria for the pathological diagnosis of lesions in rats and mice [21]

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Summary

Methods

Resolution of the controversy To address these issues, RI reexamined all lesions in Sprague-Dawley rats that had been diagnosed as. The morphological features of all lesions that had originally been diagnosed as lymphoma or leukemia were reexamined and reclassified according to the most recently updated INHAND criteria - the Internationally Harmonized Nomenclature And Diagnostic (INHAND) criteria for the pathological diagnosis of lesions in rats and mice [21]

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