The Combined Effects of Aspartame and Acesulfame-K Blends on Appetite: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Statement of Significance: In this report, we have undertaken a systematic review and meta-analysis of human appetite studies that used combinations of the NNSs aspartame and acesulfame-K, which are commonly used in foods and beverages. We found that EI is lower in Asp/Ace-K blend consumers when compared with controls; however, we could not reliably attribute changes in EI to changes in subjective appetite scores, gut peptides, or blood glucose. Higher-quality short- and long-term studies are therefore warranted. Aspartame (Asp) and acesulfame-K (Ace-K) are nonnutritive sweeteners (NNSs) commonly used in combination to replace added sugars in reduced- or low-calorie foods and beverages. Despite Asp/Ace-K blends having negligible calories, their effects on appetite have not been reviewed systematically. We therefore undertook a systematic review and meta-analysis of the metabolic effects of Asp/Ace-K blends on energy intake (EI), subjective appetite scores, blood glucose, and the incretin hormones glucose-dependent insulinotropic peptide and glucagon-like peptide. MEDLINE, Web of Science, and Cochrane CENTRAL databases (Embase, PubMed, and CINAHL) were searched (May 2021) for randomized controlled trials (RCTs). Human RCTs using Asp/Ace-K blends compared with sugar and water controls were included, whereas isolated cell and animal studies were excluded. An overall 4829 publications were identified and 8 studies, including 274 participants, were retrieved for review. The Asp/Ace-K group's EI was significantly reduced compared with sugar [mean difference (MD): -196.56 kcal/meal; 95% CI: -332.01, -61.11 kcal/meal; P = 0.004] and water (MD: -213.42 kcal/meal; 95% CI: -345.4, -81.44 kcal/meal; P = 0.002). Meta-analysis of subjective appetite scores and incretins could not be undertaken due to inconsistencies in data reporting and insufficient data, respectively, but of the 4 studies identified, no differences were observed between Asp/Ace-K blends and controls. The Asp/Ace-K group's blood glucose was nonsignificantly reduced compared with sugar (MD: -1.48 mmol/L; 95% CI: -3.26, 0.3 mmol/L; P = 0.1) and water (MD: -0.08 mmol/L; 95% CI: -0.62, 0.47 mmol/L; P = 0.78). Lower EI in participants who were predominantly healthy and assigned to Asp/Ace-K blends could not be reliably attributed to changes in subjective appetite scores. Blood glucose and incretins were also generally not affected by Asp/Ace-K blends when compared with controls. Additional short- and long-term RCTs using NNSs and sugars at dietarily relevant levels are needed. This trial was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42017061015).