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Nutrients
Volume 17
Issue 20
10.3390/nu17203251
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Systematic Review

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

by
Pauline Celine Raoul
1,
Maurizio Romano
2,
Francesca Sofia Galli
1,
Marco Cintoni
1,3,
Esmeralda Capristo
3,4,
Vincenzina Mora
5,6,
Maria Cristina Mele
1,3,7,
Antonio Gasbarrini
3,5,7 and
Emanuele Rinninella
1,3,7,*
1
Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
2
Degree Course in Dietetics, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
3
Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy
4
Obesity Disorders Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
5
Digestive Disease Center (CEMAD), Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
6
Clinical Trial Office (CTO), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
7
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(20), 3251; https://doi.org/10.3390/nu17203251
Submission received: 12 September 2025 / Revised: 13 October 2025 / Accepted: 14 October 2025 / Published: 16 October 2025
(This article belongs to the Special Issue Hot Topics in Clinical Nutrition (3rd Edition))
Versions Notes

Abstract

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.
Keywords: artificial sweeteners; inflammation; food additives; aspartame; sucralose; saccharin; acesulfame potassium; intestinal barrier; gut microbiota artificial sweeteners; inflammation; food additives; aspartame; sucralose; saccharin; acesulfame potassium; intestinal barrier; gut microbiota

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MDPI and ACS Style

Raoul, P.C.; Romano, M.; Galli, F.S.; Cintoni, M.; Capristo, E.; Mora, V.; Mele, M.C.; Gasbarrini, A.; Rinninella, E. Impact of Artificial Sweeteners on Inflammation Markers: A Systematic Review of Animal Studies. Nutrients 2025, 17, 3251. https://doi.org/10.3390/nu17203251

AMA Style

Raoul PC, Romano M, Galli FS, Cintoni M, Capristo E, Mora V, Mele MC, Gasbarrini A, Rinninella E. Impact of Artificial Sweeteners on Inflammation Markers: A Systematic Review of Animal Studies. Nutrients. 2025; 17(20):3251. https://doi.org/10.3390/nu17203251

Chicago/Turabian Style

Raoul, Pauline Celine, Maurizio Romano, Francesca Sofia Galli, Marco Cintoni, Esmeralda Capristo, Vincenzina Mora, Maria Cristina Mele, Antonio Gasbarrini, and Emanuele Rinninella. 2025. "Impact of Artificial Sweeteners on Inflammation Markers: A Systematic Review of Animal Studies" Nutrients 17, no. 20: 3251. https://doi.org/10.3390/nu17203251

APA Style

Raoul, P. C., Romano, M., Galli, F. S., Cintoni, M., Capristo, E., Mora, V., Mele, M. C., Gasbarrini, A., & Rinninella, E. (2025). Impact of Artificial Sweeteners on Inflammation Markers: A Systematic Review of Animal Studies. Nutrients, 17(20), 3251. https://doi.org/10.3390/nu17203251

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