A statistically significant increase in the incidence
of malignant tumors, lymphomas and leukemias in rats exposed to varying doses
of aspartame appears to link the artificial sweetener to a high carcinogenicity
rate, according to a study accepted for publication today by the peer-reviewed
journal Environmental Health Perspectives (EHP). The authors of the study, the
first to demonstrate multipotential carcinogenic effects of aspartame administered
to rats in feed, called for an "urgent reevaluation" of the current
guidelines for the use and consumption of this compound.
"Our study has shown that aspartame is a multipotential carcinogenic
compound whose carcinogenic effects are also evident at a daily dose of 20 milligrams
per kilogram of body weight (mg/kg), notably less than the current acceptable
daily intake for humans," the authors write. Currently, the acceptable
daily intake for humans is set at 50 mg/kg in the United States and 40 mg/kg
Aspartame is the second most widely used artificial sweetener in the world.
It is found in more than 6,000 products including carbonated and powdered soft
drinks, hot chocolate, chewing gum, candy, desserts, yogurt, and tabletop sweeteners,
as well as some pharmaceutical products like vitamins and sugar-free cough drops.
More than 200 million people worldwide consume it. The sweetener has been used
for more than 30 years, having first been approved by the FDA in 1974. Studies
of the carcinogenicity of aspartame performed by its producers have been negative.
Researchers administered aspartame to Sprague-Dawley rats by adding it to a
standard diet. They began studying the rats at 8 weeks of age and continued
until the spontaneous death of each rat. Treatment groups received feed that
contained concentrations of aspartame at dosages simulating human daily intakes
of 5,000, 2,500, 500, 100, 20, and 4 mg/kg body weight. Groups consisted of
100 males and 100 females at each of the three highest dosages and 150 males
and 150 females at all lower dosages and controls.
The experiment ended after the death of the last animal at 159 weeks. At spontaneous
death, each animal underwent examination for microscopic changes in all organs
and tissues, a process different from the aspartame studies conducted 30 years
ago and one that was designed to allow aspartame to fully express any carcinogenic
The treated animals showed extensive evidence of malignant cancers including
lymphomas, leukemias, and tumors at multiple organ sites in both males and females.
The authors speculate the increase in lymphomas and leukemias may be related
to one of the metabolites in aspartame, namely methanol, which is metabolized
in both rats and humans to formaldehyde. Both methanol and formaldehyde have
shown links to lymphomas and leukemias in other long-term experiments by the
The current study included more animals over a longer period than earlier studies.
"In our opinion, previous studies did not comply with today's basic requirements
for testing the carcinogenic potential of a physical or chemical agent, in particular
concerning the number of rodents for each experimental group (40-86, compared
to 100-150 in the current study) and the termination of previous studies at
only 110 weeks of age of the animals," the study authors wrote.
The authors of the study were Morando Soffritti, Fiorella Belpoggi,
Davide Degli Esposti, Luca Lambertini, Eva Tibaldi, and Anna Rigano of
the Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of
Oncology and Environmental Sciences, Bologna, Italy. Funding for the research
was provided by the European Ramazzini Foundation of Oncology and Environmental
Sciences, Bologna, Italy. The article is available free of charge at http://ehp.niehs.nih.gov/docs/2005/8711/abstract.html.