Can artificial sweeteners increase cancer risk? Original paper

Artificial sweeteners have long been a source of controversy, despite their approval for use in foods and beverages by authoritative bodies such as the U.S. Food and Drug Administration and the European Food Safety Authority. Among the most cited concerns is their potential to increase cancer risk. While some evidence links these sweeteners to cancer in rodents, data on humans are scarce.

This cohort study assessed the association between artificial sweetener intake and cancer risk. The authors assessed dietary intake and consumption of artificial sweeteners from 102,865 people in France twice per year between 2009 and 2021 via three nonconsecutive web-based 24-hour dietary records randomly assigned over 15 days (two weekdays and one weekend day). Baseline dietary intakes were evaluated by averaging all 24-hour dietary records during the first two years of follow-up.

The authors determined the associations based on total artificial sweetener intake (acesulfame-K, aspartame, cyclamates, saccharin, sucralose, thaumatin, neohesperidin dihydrochalcone, steviol glycosides, and salt of aspartame-acesulfame) and assessed acesulfame-K, aspartame, and sucralose individually. They included total cancer risk and risk for breast, prostate, and obesity-related cancers (colorectal, stomach, liver, mouth, pharynx, larynx, oesophageal, breast, ovarian, endometrial, and prostate cancers) as outcomes.

The authors adjusted for the following potential confounders:

• Age
• Sex (except for breast and prostate cancer analysis)
• Education level
• Physical activity
• Smoking
• BMI
• Height
• Weight gain during follow-up
• Presence of diabetes
• Family history of cancer
• Number of 24-hour dietary records completed
• Baseline intake of calories, alcohol, sodium, saturated fat, fiber, total sugar, fruits and vegetables, whole-grain foods, and dairy products

In their analysis, the authors categorized participants as “high” consumers of artificial sweeteners (those consuming above the median intake among consumers), “low” consumers (those consuming less than the median intake) and nonconsumers. The authors also categorized participants based on artificial sweeteners intake and total sugar intake (less than or at least 100 g/day) to compare the risk associated with sugar intake to that of artificial sweeteners.

Compared to nonconsumers, higher consumers tended to be younger, women, smokers, less physically active, more educated, and more likely to have prevalent diabetes. They had lower intakes of energy, alcohol, saturated fats, fiber, fruit and vegetables, and whole-grain food and higher intakes of sodium, total sugar, dairy products, sugary foods and drinks, and unsweetened nonalcoholic beverages. The main artificial sweetener used by participants was aspartame (58% of artificial sweetener intake), followed by acesulfame-K (29%) and sucralose (10%). All participants’ intakes of aspartame and acesulfame-K were below the acceptable daily intakes (ADIs) of 40 mg/kg body weight/day and 9 mg/kg body weight/day, respectively. Only 5 participants exceeded the ADI of 15 mg/kg body weight/day for sucralose. Soft drinks, table-top sweeteners, and yogurt/cottage cheese were the main contributors to total artificial sweetener intake, accounting for 53%, 29%, and 8% of intakes, respectively.

Compared to nonconsumers, high consumers had a 13% higher risk of overall cancer over a median follow-up of 7.7 years. When the authors stratified by type of sweetener, they found that aspartame and acesulfame-K were associated with a 15% and 13% higher risk for total cancer, respectively. When the authors stratified by cancer site, high consumers had a 13% higher risk for obesity-related cancers. In addition, high consumers of aspartame had a 22% higher risk for breast cancer and a 15% higher risk for obesity cancers.

The authors also found that high sugar intake was associated with increased cancer risk. However, there was no difference in risk between high consumers of artificial sweeteners consuming less than 100 grams of sugar per day and nonconsumers of artificial sweeteners consuming at least 100 grams of sugar per day. The highest risk for cancer was observed in participants with a high intake of artificial sweeteners and intake of at least 100 grams of sugar per day.

At first glance, this study suggests that artificial sweeteners can increase cancer risk, but several caveats have to be considered:

• As this was an observational study, it cannot be used to establish whether artificial sweeteners cause cancer. Though the authors did adjust for potential confounders, there may have been other confounding variables that weren’t adjusted for. For example, high artificial sweetener consumers might also have a high intake of fast food (people might order artificially sweetened beverages with their meals) or processed foods, which often contain artificial sweeteners. However, this study does justify future research into causality. As the authors note, the causal claim could be bolstered or negated by Mendelian randomization studies down the road.

• Another 2019 analysis from the same cohort found that artificially sweetened beverages were not associated with cancer, whereas sugary drink consumption was associated with cancer.^[1]

• While the results are statistically significant, it’s worth considering whether the results are clinically significant. That’s why it’s important to look at overall cancer risk for each group of participants, as opposed to relative risk. Of the 64,892 people classified as “nonconsumers,” there were 2,013 incident cases of cancer (a 3.10% risk). Of the 18,986 people classified as “low consumers,” there were 744 incident cases of cancer (a 3.92% risk). Of the 18,987 participants classified as “high consumers,” there were 601 incident cases of cancer (a 3.17% risk).

• Low consumers had a slightly higher risk for cancer than high consumers, though this difference was not tested for statistical significance. If artificial sweeteners do increase cancer risk, one would expect high consumers to be at the highest risk.

The March 2022 issue of Study Summaries includes a review that concluded artificial sweeteners were not genotoxic, meaning they don’t cause DNA or chromosomal damage, and as such are likely not carcinogenic. However, as noted in that review, that study and several other narrative and systematic reviews assessing the genotoxicity potential of artificial sweeteners were partially funded by the American Beverage Association.