Nonnutritive Sweetener Consumption, Metabolic Risk Factors, and Inflammatory Biomarkers Among Adults in the Cancer Prevention Study-3 Diet Assessment Sub-Study

Abstract

Background

Nonnutritive sweeteners (NNSs) are widely used to replace added sugars, yet their role in metabolic health and chronic disease prevention is debated.

Objective

The objective of this study was to examine associations between NNS consumption, metabolic risk factors, and inflammatory biomarkers.

Methods

This cross-sectional analysis included 624 adults in the American Cancer Society’s Cancer Prevention Study-3 Diet Assessment Substudy (DAS). Consumption of NNS, including aspartame, saccharin, sucralose, and acesulfame-potassium, was estimated using the mean quantities reported in 6 24-h dietary recalls over 1 y. Fasting insulin, C-peptide, hemoglobin A1c (HbA1c), leptin, adiponectin, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured in fasting blood samples collected twice, 6 mo apart. Multivariable linear regression was used to examine associations between NNS consumption and the mean levels of each metabolic or inflammatory biomarker. Base models were adjusted for age, sex, race, education, smoking, and physical activity; full models were further adjusted for body mass index (BMI), diet quality (Healthy Eating Index 2020), and energy intake.

Results

More than half (55%) of participants reported consuming NNS (mean daily NNS consumption 7, 38, and 221 mg across tertiles). NNS consumption was positively associated with leptin (P-trend = 0.0006) and CRP (P-trend = 0.02), but associations were attenuated after adjustment for BMI, diet quality, and energy intake. NNS consumption was not associated with insulin, C-peptide, HbA1c, adiponectin, TNF-α, or IL-10. In analyses stratified by BMI, NNS consumption was positively associated with IL-6 among participants with BMI ≥25kg/m² but not BMI <25kg/m².

Conclusions

Findings in the full sample were null after adjustment for energy intake and BMI, but NNS consumption was positively associated with IL-6 among participants with overweight or obesity. Investigation of mechanisms through which NNS consumption may impact inflammatory pathways is warranted.