Sucralose and Human Health: Metabolic, Microbiome, Neuroendocrine, Toxicological, and Environmental Perspectives

Abstract

Sucralose is a prevalent non-nutritive sweetener characterised by its chemical stability, intense sweetness, and low-calorie content, which have facilitated its global acceptance, regulatory endorsement, and an acceptable daily intake (ADI) of 5 mg/kg. However, recent data question its presumed inertness and underscore potential metabolic, microbiome, toxicological, neuroendocrine, and environmental issues. This review consolidates existing evidence on the chemistry and pharmacokinetics of sucralose, indicating minimal absorption, with the majority of the dose excreted unchanged and small amounts of glucuronide metabolites. We analyse both animal and human studies that associate sucralose with dose-dependent gut dysbiosis, particularly reductions in Bifidobacteria and Lactobacilli, as well as shifts in Bacteroidetes/Firmicutes. Additionally, we discuss altered incretin and T1R2/T1R3 signalling, hepatic insulin resistance, and glucose intolerance—effects that are more pronounced in metabolically vulnerable individuals. We assess long-term toxicological and carcinogenicity datasets that predominantly substantiate regulatory safety results while recognising methodological deficiencies and interspecies variations that hinder translation. Environmental persistence and aquatic accumulation are examined in conjunction with biodegradation techniques. We propose research priorities: standardised exposure measurements, longitudinal multi-omics in high-risk populations, mechanistic studies of sweet-taste receptor-mediated metabolic signalling, and ecological destiny analyses to guide revised risk assessment and tailored mitigation strategies.