Pomegranate Juice Induces Similar Glycemic but Distinct Incretin Responses Compared with Sugar-Water: A Randomized Crossover Trial

BACKGROUND: Pomegranate juice (PomJ) is a rich source of polyphenols, particularly ellagitannins and anthocyanins, that have been linked to metabolic benefits. However, evidence regarding its acute metabolic effects remains inconclusive. OBJECTIVE: To compare acute glycemic and incretin responses following consumption of isocaloric pomegranate juice (PomJ) and sugar-water, and to explore individual variability in glycemic response patterns. METHODS: In this randomized, controlled, crossover trial, 42 adults completed three interventions following a standardized low-polyphenol diet, which was maintained for the entire study. Participants consumed isocaloric PomJ, sugar-water, and water, in random order, each separated by a 1-week washout period. Postprandial glucose, insulin, glucagon, GLP-1, GIP, C-peptide, and triglycerides were measured over 2 hours. Glycemic and incretin responses were analyzed using mixed-effects models. Exploratory analyses, including dynamic time warping (DTW) and response stratification, were performed to characterize individual glycemic response patterns. RESULTS: , and mean fasting glucose levels of 94.9±9.7mg/dL. Mean glycemic responses did not differ between PomJ and sugar-water across conventional glycemic metrics, including netAUC, glucose peak, time of glucose peak, its duration, and the ending time of the peak (all P>0.05). However, PomJ elicited significantly lower GIP responses than sugar-water (AUC PomJ: 23.2±4066, AUC Sugar-water: 2102.0±5699, adjusted p=0.002; bonferroni correction). A participant-level permutation analysis of DTW distances demonstrated that within-participant glucose trajectories were, on average, more similar than expected under random participant pairing (within-participant DTW distance: 91.3, between-participant DTW distance was 111.3; permutation P=0.0002). Exploratory post hoc stratification identified heterogeneous glycemic response patterns, which were further characterized descriptively. CONCLUSION: Pomegranate juice produced similar glycemic but distinct incretin responses compared with sugar-water. Exploratory analyses highlighted heterogeneity in glycemic response patterns under standardized study conditions. Further repeated-measures studies are needed to determine the reproducibility and biological basis of these observations. This study was registered in clinicaltrials.gov NCT04591782.