Impact of Artificial Sweeteners on Inflammation Markers: A Systematic Review of Animal Studies.

BACKGROUND: Artificial sweeteners, widely used as non-nutritive sugar substitutes, are increasingly prevalent in ultra-processed products. Although promoted for weight management due to their minimal caloric content, their impact on systemic inflammation remains uncertain. This systematic review of animal studies aims to evaluate the association between artificial sweetener consumption and inflammatory biomarkers. METHODS: A systematic literature search was conducted up to May 2025 across PubMed, Web of Science, and Scopus, following PRISMA guidelines and registered in PROSPERO (CRD420251084004). Risk of bias was assessed using the ARRIVE guidelines and SCYRCLE's risk of bias tool. RESULTS: Thirty-seven animal studies were included: aspartame (n = 17), sucralose (n = 16), acesulfame potassium (n = 5), and saccharin (n = 4). Protocols varied in terms of dosage, exposure duration, animal models, and assessment of inflammatory outcomes, including C-reactive protein, interleukins (IL-6 and IL-1β), and tumor necrosis factor alpha. Aspartame and sucralose could elevate inflammatory markers, with sucralose also disrupting gut integrity and microbiota. Acesulfame K and saccharin showed variable, dose-dependent effects. CONCLUSIONS: This systematic review of animal studies suggests a possible mechanistic association between the consumption of certain artificial sweeteners and systemic inflammation. However, this relationship remains to be clarified and warrants exploration through well-designed, large-scale randomized controlled trials.