LC–MS Probes Link Between Artificial Sweeteners and Breast Cancer

Non-nutritive sweeteners (NNSs), or sugar substitutes, were created by the food industry to cut down on sugar and calories without losing the sweet taste. Some large population studies have hinted that consuming them might raise the risk of certain cancers, including breast cancer. However, all that evidence has come from people reporting what they ate and drank, which is not always accurate, rather than from directly measuring the sweeteners in their bodies.

To get a clearer picture, Italian researchers measured the levels of these sweeteners in urine samples from women taking part in the Moli-sani Study, a large, long-running health study, and looked at whether those levels were linked to breast cancer (BC) risk. They used liquid chromatography–mass spectrometry (LC–MS) to accurately detect and measure small amounts of specific substances. Their findings were published in the journal Nutrients.¹

What Do We Know About the Health Effects of Artificial Sweeteners?

NNSs give food and drinks a sweet taste while adding few or no calories, which is why they're often used in place of sugar.²How much of each sweetener people take in can differ widely, depending on what they eat and drink and which sweeteners go into the products they choose. These sweeteners have been promoted as a way to cut back on sugar and calories and to help people lose weight or keep it off. Studies that directly test this have generally found that swapping sugar for artificial sweeteners can help people eat fewer calories and lose a little weight, especially when they're used in place of sugary foods and drinks.³However, the research on whether these sweeteners might harm our metabolism is mixed. The results may depend on which sweetener is being studied, how much is consumed, what it's being compared with, and who is taking part in the study.⁴

Some long-term studies that follow people over time have found links between consuming artificial sweeteners and certain cancers, although the results have been inconsistent.^3,5,6In addition, according to the authors of the study,¹ “these studies have largely relied on self-reported dietary information, which may introduce exposure misclassification and may not accurately capture exposure to individual NNSs from different dietary sources.”

Are Artificial Sweeteners Linked to Breast Cancer Risk?

The researchers involved in this study randomly picked 988 middle-aged women (around 55 years old on average) from the study to serve as a comparison group. They then compared them with 272 women who went on to develop breast cancer, 38 of whom had not yet gone through menopause and 234 who had. Using LC–MS, the team tested urine samples collected when the women first joined the study, between 2005 and 2010, for six common sweeteners: aspartame, acesulfame, saccharin, sucralose, cyclamate, and stevia-based sweeteners. The measurements were adjusted to account for how concentrated each urine sample was.¹

For each sweetener, the researchers simply noted whether it was present or not. They then added these up to give each woman a total score from 0 to 6 and grouped the scores as low (0 to 1 sweeteners detected) or high (2 or more). Finally, they used statistical methods to estimate whether the presence of these sweeteners was linked to a higher risk of breast cancer, while taking other factors that could affect risk into account.¹

Saccharin was by far the most common sweetener found in the women's urine, making up about three-quarters of all the sweeteners detected. Stevia-based sweeteners came in a distant second, at around 11%.¹

After accounting for other factors that could affect cancer risk, the researchers found no link between breast cancer overall and any of the individual sweeteners, or between breast cancer and the total amount of sweeteners detected. Women with higher sweetener scores were no more likely to develop the disease than those with lower scores.^`

There was, however, one exception. Among women who had not yet gone through menopause, those with sucralose in their urine appeared to have roughly six times the risk of breast cancer (although the research team pointed out that this finding was based on just 38 women with cancer in that group, so the estimate is very uncertain and should be treated with caution).¹

“Urinary NNS concentrations,” write the authors of the paper,¹ “were not associated with overall BC risk. The observed association between urinary sucralose and premenopausal BC should be considered exploratory and hypothesis-generating and requires independent replication.”

Read More on Similar Topics
Rapid Tissue Culture and UPLC-MS/MS Analysis for Stevia Glycoside Production

References

• Bonaccio, M.; Di Castelnuovo, A.; Costanzo, S. et al. Urinary Concentrations of Non-Nutritive Sweeteners and Breast Cancer: A Case-Cohort Analysis of the Moli-sani Study. Nutrients 2026, 18 (18), 2958. DOI: 10.3390/nu18182958
• 2.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
• Greyling, A.; Appleton, K. M.; Raben, A. et al. Acute Glycemic and Insulinemic Effects of Low-energy Sweeteners: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Clin Nutr. 2020, 112 (4), 1002-1014. DOI: 10.1093/ajcn/nqaa167
• Azad, M. B.; Abou-Setta, A. M.; Chauhan, B. F. et al. Nonnutritive Sweeteners and Cardiometabolic Health: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Prospective Cohort Studies. CMAJ 2017, 189 (28), E929-E939.DOI: 10.1503/cmaj.161390
• 5.Palomar-Cros, A.; Straif, K.; Romaguera, D. et al. Consumption of Aspartame and Other Artificial Sweeteners and Risk of Cancer in the Spanish Multicase-control Study (MCC-Spain). Int J Cancer 2023, 153 (5), 979-993. DOI: 10.1002/ijc.34577
• Hodge, A. M.; Bassett, J. K.; Milne, R. L. et al. Consumption of Sugar-sweetened and Artificially Sweetened Soft Drinks and Risk of Obesity-related Cancers. Public Health Nutr. 2018, 21 (9), 1618-1626. DOI: 10.1017/S1368980017002555