March 25, 2019 — Rosanne Rust MS, RDN, LDN
Aspartame, a low calorie sweetener that has been on the US market since 1983, has been widely studied and approved for human consumption by various worldwide regulatory agencies, [yet studies continue to review its potential carcinogenicity and safety. It’s clearly important to carefully review studies and research to ensure the use of aspartame, which has been approved in over 90 countries, does not pose a threat to individuals or public health.
Here, I’m summarizing the results from three studies published in the April 2019 issue of the journal, Regulatory Toxicology and Pharmacology (and partially funded by the Calorie Control Council), that evaluated the genotoxicity and carcinogenicity of aspartame: Mutagenicity and genotoxicity studies of aspartame, Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria, and Systematic review and evaluation of aspartame carcinogenicity bioassays T using quality criteria.
The study (by Otabe, et al) evaluating mutagenicity and genotoxicity confirmed that aspartame is considered to be non-genotoxic. A genotoxin is a poisonous substance which damages DNA, and can potentially cause mutations in DNA and cancer. In the study, 54 mice were given various doses of aspartame as either a single dose of 0 (vehicle control), 500, 1000, or 2000 mg aspartame/kg body weight. Mice were euthanized at 24 or 48 hours, at which time bone marrow was evaluated.
The authors used the Ames test to evaluate potential genotoxicity. The Ames test was developed in the laboratory of Bruce Ames, a renowned biochemist specializing in cancer researcher, out of the University of California, and evaluates strains of Salmonella bacteria, which have unique features that promote sensitivity to test chemicals. The cell walls of these bacteria have increased permeability to allow easier access of chemical agents to the cells’ DNA, which can increase potential cancer risk. The test also can assess a bacterial strain using a repair-deficient variant of the bacterium E. coli.
The results from this study showed that aspartame in non-mutagenic (does not cause genetic effects). Even oral administration of aspartame at doses of up to 2000 mg/kg body weight had no effect on cytotoxicity to bone marrow cells.
The review study, “Systematic review and evaluation of Aspartame carcinogenicity bioassays using quality criteria,” assessed cancer studies about aspartame based on a quality appraisal and also used the Klimisch grading system. This grading system ranks reliability of study findings based on how well or poorly a study was designed.
A total of nine studies were reviewed. Three of the nine were Ramazzini Institute studies and were scored as “not reliable” in concluding aspartame was linked to cancer in lab animals. The three National Toxicology Program studies on transgenic mice, and the three Searle studies, (two years long) concluded aspartame is safe, and received a score of “reliable with restrictions.” Of course, there are always limitations with rodent studies, but it’s important to evaluate and consider overall reliability of a study’s methodology.
“Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria” provides a review of current epidemiology research to determine those of the highest quality. The authors evaluated 42 publications that appeared to address the carcinogenic potential of aspartame to humans. Studies were reviewed using a quality appraisal tool for the evaluation of case-control and cohort epidemiology studies from the National Heart Lung and Blood Institute (NHLBI) of the National Institute of Health (NIH), to determine which studies were of highest quality. 
The studies evaluated dietary factors and cancer and included epidemiological studies, ecological studies, and case-controlled studies. Ecological studies attempt to correlate an increase in the incidence of cancer in a general population to some exposure event. A case-controlled study is a study that compares patients who have a disease (or outcome of interest) with patients who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group to determine the relationship between the risk factor and the disease.
These were human studies evaluating diet and cancer. The investigators narrowed the review down to two case-control studies and five prospective cohort studies that were determined most reliable in terms of quality. Most of the studies administered aspartame via low-calorie or diet beverages or sweetener packets.
These studies also included many lifestyle and dietary factors that could be related to cancer. Many of the case-controlled studies did not isolate aspartame, and in some cases it wasn’t even indicated in the food intake record. Although diet soda is a common way humans consume aspartame, some of the higher quality studies were still limited in that they used diet beverages sweetened with aspartame and not aspartame itself.. The NHLBI quality appraisal tool narrowed their review to seven studies which had a clear research objective, acceptable number of subjects and controls in sufficient numbers, and demonstrated reasonable exposure to beverages known to include aspartame. The findings of these studies, consistent with results from Bernardo et al, don’t support the hypothesis that low-calorie beverages (and therefore aspartame) are associated with increased risk of cancer.
Keep in mind that aspartame is hydrolyzed in the gut to common amino acids (aspartic acid and phenylalanine) and trace amounts of methanol, which are metabolized via normal well-characterized endogenous metabolic pathways.
Toxicological testing conducted to determine whether or not a food additive is safe for human consumption involves testing for its potential to cause genetic damage. These recent reviews conclude that there is a large body of evidence that shows aspartame is non-mutagenic in mice, and non-carcinogenic to humans. Even though aspartame had been extensively studied prior to its approval in 1981, new studies are done to re-assess aspartame with the most current internationally-established guideline protocols for genetic toxicity. Using the most up-to-date technology and well-accepted protocols, these new mice studies offer strong evidence that aspartame does not cause genetic effects.
When considering the highest quality epidemiological and case-controlled studies over time, there appears to be no increased cancer risk in diets that include aspartame, or that low-calorie beverages (and therefore aspartame) are associated with increased risk of cancer.
Rosanne Rust MS, RDN, LDN is a registered, licensed dietitian-nutritionist with over 25 years experience. Rosanne is a paid contributor to Allulose.org. As a Nutrition Communications Consultant she delivers clear messages helping you understand the science of nutrition so you can enjoy eating for better health. Rosanne is the co-author of several books, including DASH Diet For Dummies® and the The Glycemic Index Cookbook For Dummies®. A wife, and mother of 3 boys, she practices what she preaches, enjoying regular exercise, good food and festive entertaining. Follow her on Twitter @RustNutrition.