Published Review Provides Further Evidence Aspartame Not Associated with Increased Risk of Cancer

Medizin Dozent in einer Weiterbildung vor Studenten und jungen Ärzten

March 22, 2019 — The continuing study of low- and no-calorie sweeteners (LNCS) allows researchers to utilize the most precise and scientifically relevant research methodologies to evaluate the safety and efficacy of these ingredients for human consumption. The latest publication by Haighton et al. (2019), “Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria,” provides further evidence that aspartame is not associated with an increased risk of cancer in humans.

This Study Differs From Previous Reviews
Haighton et al. (2019) published “Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria” in the same issue of Regulatory Toxicology and Pharmacology in which this current paper appears, and is summarized here. The former review was based exclusively on studies using whole animals, and the studies were assessed against the Klimisch grading system to rank the credibility of their findings on aspartame’s possible link to cancer.  However, all of the studies selected for inclusion in this review were conducted exclusively in humans.

This study also differs from the systematic review by Bernardo et al (2016) evaluating adverse effects in adult and child consumers of LNCS compared to individuals who were not consumers because Bernardo et al. used the Castle Ottawa Scale and Oxford classification to assess the quality of the studies under consideration. Haighton et al. used the National Heart, Lung and Blood Institute of the National Institute of Health (NHLBI, 2014a,b) quality appraisal tool. They included all of the cancer epidemiology studies covered by Bernardo et al. in their review plus other relevant publications identified in a literature search. The value of using different quality appraisal tools designed for the evaluation of case-control and cohort epidemiology studies is their specific focus on the methodology of the published research, such as the recruitment of subjects, methods of data collection, and data analysis with respect to validity of the study. The criteria used in different appraisal tools also help to identify studies that were conducted with a suitable design for hazard and risk assessments.

Findings Assessed from Most Robust Studies and Compared With Previous Research
“The objective of the current research was to conduct a comprehensive analysis of the available epidemiology studies of aspartame using the National Institute of Health quality appraisal tool to assess quality. The findings determined from the most robust studies will be reviewed in assessing potential carcinogenic risks of aspartame consumption and compared to results of studies which were assessed using Castle Ottawa Scale and Oxford classification.”

Recall, Lack of Total Diet Assessment among Challenges
It is difficult to demonstrate a causal relationship between exposure to a chemical agent and carcinogenicity in humans due to the numerous confounding variables created by factors such as personal behavior, lifestyle, and environment. Evidence of carcinogenicity is further confounded by reliance on recall for consumption or exposure data, long latency times for tumor development, concurrent exposure to other possible carcinogens, and the lack of a clear dose-response relationship.

When evaluating the studies about aspartame consumption and cancer risk the researchers reported additional variables that clouded their work. These included:

  • Consumption of “diet beverages” or “diet drinks” used as a surrogate for aspartame since it is commonly found in diet soda, even though it is not as common in other diet, light, and reduced calorie beverages
  • Use of “packets” of LNCS counted as exposure without distinguishing type or brand
  • Consumption of aspartame from other sources, such as in food, candy, nutritional supplements, and medications, not investigated
  • Previous and/or continued exposure to saccharin and cyclamates, which had been on the market (in the U.S.) for over ten years before aspartame was introduced in 1981, not investigated
  • Exposure to the other LNCS that have been introduced (in the U.S.) since aspartame, including acesulfame potassium, advantame, allulose, monk fruit, neotame, sucralose, and stevia, not investigated

These complex variables can partially explain why it is so easy for results of a study to be exaggerated if it appears to have uncovered a previously undetected  associated with aspartame consumption, when, in fact, the study did not measure absolute aspartame consumption in humans. More importantly, they clearly justify the need for precise criteria to review and compare studies, as was done by Haighton et al., to see if they provide viable data from which conclusions can be drawn and supported.

In Summary: Consumption of Diet Drinks with Aspartame Not Associated with Increased Cancer Risk
The studies identified for this systematic review include eight case-controlled studies and five prospective cohort that assessed diet beverages or LNCS where it could be reasonably assumed that aspartame exposure occurred. Of these, two of the case-controlled and all of the five prospective studies were found to have a clear research objective, acceptable recruitment of patients and controls in sufficient numbers, and demonstrated a reasonable approximation of exposure to beverages known to include aspartame and analysis of the data compared to controls.

The results of these seven studies, once assessed using NHLBI criteria, are in general agreement that consumption of diet drinks or use of packets of LNCS, and by association, aspartame, is not associated with an increased risk of cancer in humans. These findings are in agreement with those reported by Bernardo et al. (2016) and with the conclusions reached by the original FDA panel (U.S.FDA, 1981) based on animal studies available at the time and those of the European Food Safety Authority (ESFA, 2013) following their comprehensive evaluation of aspartame as a food additive.

The authors of this review conclude that epidemiology studies do not suggest an increased risk of the cancers examined with aspartame consumption.


Haighton L, Roberts A, Jonaitis T, Lynch B. Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria. Reg. Tox. and Pharm. 2019; 103:(353-362)

Haighton, Roberts A, Walters B, Lynch B. Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria. Reg. Tox. and Pharm. 2019; 103:(332-344)

Bernardo WM, Simoes RS, Buzzini RF, Nunes VM, Glina FPA. Adverse effects of the consumption of artificial sweeteners – systematic review. Rev. Assoc. Med. Bras. 2016; 62:(120-122)

Magnuson BA, Burdock GA, Doull J., et al. (7). Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit. Rev Tox. 2007; 37:(629-727)

U.S. FDA, 1981. Aspartame: commissioner’s final decision; Notice: final decision following a hearing before a public board of inquiry [Docket No. 75F-0355]. Fed. Regist. (US) 46 (142), 38283-38308

ESFA, 2013. Scientific opinion on the re-evaluation of aspartame (E 951) as a food additive (ESFA Panel on food additives and nutrient scores added to food/ANS) (question no. EFSA-Q-2008-1522, etc.) ESFA J. 11(4), 3496. (263 pp.)


Robyn Flipse, MS, MA, RDN is a registered dietitian, cultural anthropologist and scientific advisor to the Calorie Control Council, whose 30+ year career includes maintaining a busy nutrition counseling practice, teaching food and nutrition courses at the university level, and authoring 2 popular diet books and numerous articles and blogs on health and fitness. Her ability to make sense out of confusing and sometimes controversial nutrition news has made her a frequent guest on major media outlets, including CNBC, FOX News and USA Today. Her passion is communicating practical nutrition information that empowers people to make the best food decisions they can in their everyday diets. Reach her on Twitter @EverydayRD and check out her blog The Everyday RD.

Items of Interest

March 22, 2019 Professional Research, Research Summaries