Effects of Short-Term (14-Day) Intake of Sucrose and Non-Caloric Sweeteners on Glucose Regulation, Blood Lipids, Gut Hormones, Inflammation Markers, and Appetite in Healthy Adults: A Randomized Controlled Trial

Background/Objectives: Non-caloric sweeteners are increasingly used as alternatives to sugar to reduce energy intake, yet their metabolic effects remain controversial. This study aimed to evaluate the effects of sucrose, saccharin, and steviol glycosides on glucose regulation and cardiometabolic risk markers in healthy adults. Methods: In a randomized, double-blind, crossover trial, 39 healthy, normal-weight adults consumed beverages containing sucrose (66 g/day), saccharin (220 mg/day), or steviol glycosides (220 mg/day) for 14 days, with washout periods between interventions. Metabolic outcomes were assessed at baseline and after each intervention under fasting conditions and during a 2 h postprandial test. Primary outcomes were glucose and insulin responses; secondary outcomes included gut hormones, lipids, inflammatory markers, and subjective appetite. Results: Compared with baseline, fasting glucose increased after sucrose and saccharin, and fasting insulin increased after stevia (p < 0.01). All interventions increased postprandial insulin responses and reduced indices of insulin sensitivity (p < 0.05). Fasting PYY and GLP-2 increased following all treatments (p < 0.001), without differences between sweeteners. Triglycerides were higher after sucrose than saccharin (p < 0.05), while no differences were seen for cholesterol, apolipoproteins, or CRP. Appetite ratings were unchanged, with a trend (p = 0.053) towards a reduced desire to eat after stevia in the late postprandial phase. Conclusions: Short-term intake of sucrose and non-caloric sweeteners resulted in broadly similar metabolic responses, with no significant differences in glucose regulation. However, triglyceride concentrations were higher following sucrose than saccharin, whereas no consistent differences were observed across the remaining outcomes. Observed deviations from baseline should be interpreted with caution. Further long-term studies in diverse populations are warranted.