Beyond sweetness: A review of the health and safety of acesulfame-K.

Acesulfame‑potassium (Ace-K) is a high-intensity, non-nutritive sweetener widely used in beverages and processed foods for its stability, synergistic sweetness, and negligible caloric value. Regulatory agencies such as EFSA and JECFA have established an ADI of 0-15 mg/kg bw/day; however, emerging evidence calls for a nuanced understanding of its biological impact. This review consolidates data from in vitro, in vivo, and human studies to critically evaluate the metabolic, hepatic, neurobehavioral, pancreatic, and microbiota-related effects of Ace-K. Although human studies generally confirm its safety within the ADI range, preclinical models have reported alterations in gut microbiota composition, lipid metabolism, and inflammatory and gene-expression pathways; often at supraphysiological levels. Evidence also indicates placental and lactational transfer, warranting attention to early-life exposure. Matrix and co-sweetener interactions further influence their stability and physiological response. Overall, Ace-K appears chemically stable and well-tolerated in humans, but uncertainties remain regarding chronic, cumulative, and population-specific risks. Future studies should employ multi-omics, dose-relevant human designs to bridge mechanistic and epidemiological gaps.