Association of Low-Calorie Sweeteners with Selected Circulating Biomarkers of Intestinal Permeability in The Cancer Prevention Study-3 Diet Assessment Substudy.

Background: Low-calorie sweeteners (LCS) are popular sugar substitutes and have been shown to alter the gut microbiota, which raises concerns about potential impacts on intestinal permeability.

Objectives: To examine cross-sectional associations between LCS consumption and circulating biomarkers of intestinal permeability.

Methods: We analyzed data from 572 U.S. adults participating in the Cancer Prevention Study-3 Diet Assessment Substudy who provided up to two fasting blood samples, collected six months apart, to measure biomarkers of intestinal permeability including antibodies to flagellin (anti-flagellin), lipopolysaccharide (anti-LPS), and total antibodies; and up to six 24-hour dietary recalls, collected over the course of 12 months, to estimate average intake of LCS including aspartame, sucralose, acesulfame-potassium, and saccharin. Multivariable linear regression, adjusted for sociodemographic characteristics, lifestyle factors and medical history, was used to examine associations between LCS consumption and levels of intestinal permeability biomarkers by comparing mean differences in biomarkers among lower (>0 to ≤50 percentile) (n=158) and higher (>50 percentile) LCS consumers (n=157) compared with non-consumers. A linear trend across non-consumers and the two consumption categories was evaluated using a continuous variable based on the median LCS intake (median= 0, 11.3 and 124.2 mg/day for non-, lower and higher consumers, respectively).

Results: Among the 572 study participants, the mean age was 52.5 years, 63.3% were female, 60.7% were on-Hispanic White, and 55.1% reported consuming LCS-containing products. Greater LCS consumption was not associated with anti-flagellin, anti-LPS, or total antibodies. Additionally, no associations between specific types of LCS and intestinal permeability biomarkers were observed.

Conclusion: The results of our study did not demonstrate an association between LCS consumption and intestinal permeability biomarkers. Further research with larger sample sizes and randomized controlled trials is needed to confirm our findings.