Urinary Concentrations of Non-Nutritive Sweeteners and Breast Cancer: A Case-Cohort Analysis of the Moli-sani Study.

Background

Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has exclusively relied on self-reported dietary information rather than objective measurements of NNSs. We examined the association of urinary concentrations of NNS with BC risk in women from the large Moli-sani Study.

Methods

Using a case-cohort design, a sample of 988 middle-aged women (mean age 55 ± 12 y) was randomly selected as a sub-cohort and compared to 272 women with incident BC (38 premenopausal and 234 postmenopausal). A total of 6 commonly used NNSs (i.e., aspartame, acesulfame, saccharin, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography-mass spectrometry in spot urine samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005-2010). The multivariable hazard ratios (HRs) were estimated using weighted Cox regression models for the case-cohort design, with each NNS modelled as a binary variable (i.e., presence vs. absence). The sum of these values produced a total urinary NNS score, which could range from 0 to 6, and was further categorised as low (0-1) or high (2-5).

Results

The predominant NNS detected in urine was saccharin (E954), contributing to 77% of total NNSs, followed by steviol glycosides (E960;11%). In multivariable-adjusted Cox analyses, neither individual NNSs nor total NNS urinary concentrations were associated with overall BC risk (HR = 1.09; 95% CI 0.80-1.48 for high vs. low). However, the presence of sucralose (E955) was directly linked to premenopausal BC (HR = 5.90; 95% CI 1.44-24.20; p = 0.014), although this estimate was based on only 38 cases and was imprecise.

Conclusions

Urinary NNS concentrations 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.