Artificial Sweeteners Are Associated With Increased Cancer Risk, Finds Large-Scale Cohort Study

Artificial sweeteners are consumed by millions of people each day as a way to reduce their calorie intake and prevent issues such as tooth decay. The food and beverage industry is aware of peoples’ desire for “sugar-free” options, and now many different products ‒ from beverages, desserts to ready meals ‒ include sweeteners in an effort to retain the sugary, sweet taste so many of us crave.

Now, results from a large cohort study of >100,000 French adults suggest that artificial sweeteners found in many foods and beverages may be associated with an increased risk of cancer. The findings were published in PLOS Medicine.

Safety measures and ongoing debate

All artificial sweeteners must undergo and pass a safety evaluation in the European Union before they can be used. Similarly, in the United States, high-intensity sweeteners (those providing “high” sweetening power yet little energy) must receive approval from the US Food and Drug Administration before they can be incorporated into food and/or beverages as additives.

Despite these measures, conflicting results from recent studies have reinvigorated the debate on the safety of artificial sweeteners and health agencies, such as the European Food Safety Authority,  are now reassessing several sweeteners previously approved.

“Some observational studies have previously investigated the associations between cancer risk and the consumption of artificially sweetened beverages (used as a proxy) and found increased risk of cancer, suggesting that artificial sweeteners present in these types of beverages might play a role in the development of cancer,” notes Dr. Mathilde Touvier, research director at the French National Institute of Health and Medical Research (INSERM) and senior author of the study.

She adds, “In addition, previous findings in animal models and in vitro / in vivo studies also suggested their carcinogenicity. Results from these studies remain constrated and there is a lack of human data. There is no epidemiological study so far (to our knowledge) that has quantified the total exposure to artificial sweeteners (from all dietary sources) and its association with cancer risk.”

To that end, the researchers assessed the presence of artificial sweeteners, including the well-known sweetener aspartame and various others, acesulfame-K, sucralose, etc., in a variety of products. The study’s first author, Charlotte Debras, highlights some these sources, “Soft drinks with no added sugars, table-top sweeteners and yogurt/cottage cheese were the main contributors to total artificial sweeteners, accounting for 53%, 29% and 8% of intakes, respectively.”

Assessing the potential carcinogenicity of artificial sweeteners

To assess the potential carcinogenicity of artificial sweeteners, the team analyzed data from French adults (N = 102,865; average age at baseline was 42.2 (±14.5) years) participating in the NutriNet-Santé study. This is a web-based cohort focused on the link between nutrition and health. Participants were responsible for self-reporting information on their health, sociodemographic, diet, lifestyle, etc.

The participants were required to provide a 24-hour dietary record, which was used by the researchers to determine individuals’ consumption of artificial sweetener, and cancer diagnosis information was recorded during follow-up.

The authors note in the study that, due to the possibility that “some participants with subclinical cancer may get sick and change their dietary habits during the months preceding their diagnosis” they performed a sensitivity analysis ‒ with follow-up starting at the age of the participants’ entry into the cohort plus two years – to address a potential reverse causality bias. Reverse causation describes the “processes through which a causal relationship operates in a way opposite to that which is apparent.”

Debras highlights that 78.5% of the participants included in the analysis were women, which could be considered a selection bias. Additional biases noted by the researchers were that participants were more likely to have higher educational levels, and to demonstrate health-conscious behaviors.

Participants were categorized to allow the team to assess cancer risk versus sweetener intake. Debras elaborates, “Since a substantial proportion of the population were non-consumers of artificial sweeteners, participants were divided into three groups: non-consumers, lower consumers and higher consumers, the latter two being separated by the sex-specific median of consumption in the study population.”

Analyses were performed for the "total of artificial sweeteners" (i.e., the sum of acesulfame-K, aspartame, sucralose, cyclamates, saccharin, steviol glycosides and salt of aspartame-acesulfame) and then separately for the most represented artificial sweeteners in the cohort (aspartame, acesulfame-K and sucralose). “Aspartame was the main artificial sweetener, contributing to 58% of intakes, followed by acesulfame-K (29%) and sucralose (10%),” explains Debras.

The researchers found that participants consuming larger amounts of artificial sweeteners (particularly aspartame and acesulfame-K), had an increased overall risk of cancer compared to non-consumers. In relation to this finding, Debras emphasizes that “aspartame and acesulfame-K were by far the most frequently consumed artificial sweeteners. Thus, the fact that associations were observed for these two (and not for sucralose, for instance) should be considered with caution since it may only be due to the fact that aspartame and acesulfame-K were the most commonly consumed.”

Aspartame was specifically associated with an increased risk of breast and obesity-related cancers.

Further investigation

While the team does not plan on studying the safety of artificial sweeteners in pediatric populations, Touvier notes that she “hopes that this will be done in other studies in the world”.

In terms of additional research, the researchers are conducting various studies based on data gathered from the NutriNet-Santé cohort. According to Touvier they plan “to investigate the associations between artificial sweeteners and other pathologies (e.g., cardiovascular diseases, diabetes) as well as investigate the mechanisms underlying these associations with mechanistic epidemiology (assessment of inflammation, oxidative stress, metabolic perturbations and gut microbiota composition) and investigate other food additives and mixtures of additives in association with health outcomes.”

Reference: Debras C, Chazelas E, Srour B, et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLoS Med. 2022;19(3):e1003950. doi: 10.1371/journal.pmed.1003950

Charlotte Debras and Dr. Mathilde Touvier were speaking with Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.