Artificial Sweeteners: A Modifiable Cancer Risk?

Marlene Busko 

March 24, 2022

March 31, 2022 // Editor's note: In paragraph 3, the story previously erroneously said there was a 22% increased risk of overall cancer, rather than breast cancer. 

People with higher (above the median) consumption of artificial sweeteners — especially aspartame and acesulfame-potassium (acesulfame-K) — had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer compared with not consuming any of these sweeteners.

These findings from the Nutri-Santé population-based observational study in France were published online March 24 in PLoS Medicine.

"Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect," Charlotte Debras at the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, France, and colleagues write.

"Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies," they continue.

Commenting to the UK Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston Medical School, Aston University, UK, said: "This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks."  

It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message."

"Important Analysis, Interpret With Caution"

"I think that this is an important analysis, but the results need to be interpreted with caution," another expert, John L. Sievenpiper, MD, PhD, associate professor, Departments of Nutritional Sciences and Medicine, University of Toronto, Ontario, Canada, told Medscape Medical News in an email.

"Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality," he explained. This is "a caveat that is well recognized by investigators in this field...and guideline and policymakers," he added.

Reverse causality is a possibility because "it is likely that many high consumers of low and no calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy," he added, "as opposed to these sweeteners causing obesity and its complications (including cancers)."

His team recently published a Diabetes and Nutrition Study Group (DNSG)-commissioned systematic review and meta-analysis of 17 randomized controlled trials. Their findings "suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes," states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming this fall. 

"The bottom line" for the current study, according to Sievenpiper, "is that it is difficult to disentangle the signals for low and no calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns."

Conflicting Results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Debras and colleagues write.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones — aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types — breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

"Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant [body mass index] BMI status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and postmenopause), ovarian, endometrial, and prostate cancers," the researchers explain.

According to a recent study, "obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women," Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3358 incident cancers — 982 breast, 403 prostate, and 2023 obesity-related cancers — were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio [HR], 1.13; 95% CI, 1.03 - 1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03 - 1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01 - 1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01 - 1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01 - 1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00 - 1.28; P = .036).

The researchers acknowledge that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by the following public institutions: Ministère de la Santé, Santé Publique France, Inserm, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement, Conservatoire National des Arts et Metiers, and Université Sorbonne Paris Nord. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council,  the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council), and the International Sweeteners Association.

PLoS Med. Published online March 24, 2022. Article

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