First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

Soffritti, Morando; Belpoggi, Fiorella; Esposti, Davide Degli; Lambertini, Luca; Tibaldi, Eva; Rigano, A

doi:10.1289/ehp.8711

Cited by 212 publications

(194 citation statements)

References 30 publications

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“…The authors state, based on the results of their study, that aspartame induces cancer in the livers and lungs of male Swiss mice, reiterating their previous conclusions that aspartame is a carcinogenic agent in rodents (Soffritti et al, 2006(Soffritti et al, , 2007. Halldorsson et al (2010) investigated preterm delivery in a cohort of 59 334 pregnant Danish women.…”

Section: Assessment 1 Introductionmentioning

confidence: 92%

Statement of EFSA on the scientific evaluation of two studies related to the safety of artificial sweeteners

2011

EFS2

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The European Food Safety Authority was asked to provide scientific advice on two studies, namely a carcinogenicity study in mice (Soffritti et al., 2010) and a prospective cohort study on the association between intakes of artificially sweetened soft drinks and preterm delivery (Halldorsson et al., 2010) and to conclude on the need to revise previous evaluations of aspartame or of the other sweeteners authorised in the European Union. The study by Soffritti et al. (2010) is a long‐term carcinogenicity study in mice with transplacental exposure to the artificial sweetener aspartame. The authors concluded that, based on their results, aspartame induces cancer in the livers and lungs of male Swiss mice. EFSA has evaluated this carcinogenicity study and has concluded that, on the basis of the information available in the publication, the validity of the study and its statistical approach cannot be assessed and that its results cannot be interpreted. Furthermore, in view of the generally recognised lack of relevance for human risk assessment of the type of tumours observed in Swiss mice when they are induced by non‐genotoxic compounds, EFSA concluded that the results presented in Soffritti et al. (2010) do not provide a sufficient basis to reconsider the previous evaluations by EFSA on aspartame. Halldorsson et al. (2010) investigated preterm delivery in a cohort of 59 334 pregnant women. The authors concluded that their results show an association between intake of artificially sweetened soft drinks and preterm delivery in the cohort. EFSA assessed this study and concluded that there is no evidence available to support a causal relationship between the consumption of artificially sweetened soft drinks and preterm delivery and that additional studies are required to reject or confirm an association. Overall, EFSA concluded that the information available from the Soffritti et al. (2010) and Halldorsson et al. (2010) publications do not give reason to reconsider the previous evaluations of aspartame or of other food additive sweeteners authorised in the European Union.

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Section: Assessment 1 Introductionmentioning

confidence: 92%

Statement of EFSA on the scientific evaluation of two studies related to the safety of artificial sweeteners

2011

EFS2

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“…c Soffritti et al, 2006. For the reasons discussed above, Caldwell et al [2008] do not make a convincing argument that the lymphomas and leukemias described in the ERF studies of MTBE and aspartame are treatment-related. …”

Section: To the Editormentioning

confidence: 97%

Comment on “Evaluation of evidence for infection as the mode of action for induction of rat lymphoma” by Caldwell et al. [2008]

Goodman¹,

Beyer²,

Beck³

2008

Environ and Mol Mutagen

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“…Lesions of the kidney and olfactory epithelium are extremely rare in this strain of rats and therefore merit special attention'. Also: Mead (2007) and Soffritti et al (2006) wrote 'The carcinogenic effects were evident at daily doses as low as 400 parts per million, equivalent to an assumed daily human intake of 20 milligrams per kilogram body weight (mg/kg). This dosage is much less than the acceptable daily intake for humans, with current limits set at 50 mg/kg in the United States and 40 mg/kg in Europe.…”

Section: Comments Of Jd Fernstrommentioning

confidence: 99%

Addressing comments by JD Fernstrom

Humphries

Pretorius

2008

Eur J Clin Nutr

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The issue of aspartame safety has been controversial since approval by FDA, many years ago. It seems as if there are two points of views, either supporting the use of aspartame, or suggesting its dangers. Numerous research articles raised concerns regarding the adverse effects and particularly related to the metabolic components. The comments of JD Fernstrom will now be addressed in Box 1.From the comments made by JD Fernstrom, it appears that he does not trust research suggesting that aspartame may be detrimental to human health. We believe that there are numerous well-researched papers by key researchers that prove the negative effects of this sweetener. Can we as researchers really take the responsibility of the health of millions of consumers by ignoring research? Can we sit back ), and we acknowledge the fact that there are articles that propagate the fact that aspartame is safe, it was the focus of the article to discuss possible adverse effects of the consumption of aspartame. Formate is not converted to diketopiperazine (abstract) Sentence in the abstract of Humphries et al. (2007) is as follows: methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. This sentence does not imply that formate is converted to diketopiperazine, but that diketopiperazine is a breakdown product of methanol. (Prodolliet and Bruelhart, 1993;Lin and Cheng, 2000). The authors are incorrect in stating that tyrosine cannot be synthesized in brain from phenylalanine. This statement is not true; under the heading 'Effects of phenylalanine', the sentence reads 'A large number of compounds, including phenylalanine and tyrosine compete with each other for a binding site on the NAAT, seeing that it is the only manner in which these compounds can cross the BBB. Importantly, tyrosine cannot be synthesised in the brain, thus have to enter the BBB via NAAT (Figure 2c) for production'. For more clarity, the sentence could also have read 'Importantly, dopamine cannot be synthesized in the brain unless tyrosine is carried over the BBB via NAAT for production'. Despite the authors' statement, even very large increases in phenylalanine levels produced by aspartame administration to rats do not suppress catecholamine synthesis rate (Dow-Edwards et al., 1989) Reference: There are papers that disagree with the statement of JD Fernstrom: Yokogoshi and Wurtman (1986), which states 'Phenylalanine has been described as both a substrate (Kaufman S, personal communication) and an inhibitor (McKean, 1972;Gibson and Wurtman, 1977) of tyrosine hydroxylase, the enzyme that catalyzes the rate-limiting step in converting tyrosine to catecholamines'. 'The effect of TPT (tryptophan, phenylalanine and tyrosine) depletion on the ratio between the monoamine precursors and other LNAA that compete for active transport into the brain correspond to an 87-90% decrease. Neuro-imaging, cerebro...

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First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

Cited by 212 publications

References 30 publications

Statement of EFSA on the scientific evaluation of two studies related to the safety of artificial sweeteners

Statement of EFSA on the scientific evaluation of two studies related to the safety of artificial sweeteners

Comment on “Evaluation of evidence for infection as the mode of action for induction of rat lymphoma” by Caldwell et al. [2008]

Addressing comments by JD Fernstrom

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