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

Pomegranate juice (PomJ) is a rich source of polyphenols, particularly ellagitannins and anthocyanins, which have been linked to metabolic benefits. However, evidence regarding its acute metabolic effects remains inconclusive.

This study aimed to compare acute glycemic and incretin responses after consumption of isocaloric PomJ and sugar water, and to explore individual variability in glycemic response patterns.

In this randomized, controlled, crossover trial, 42 adults completed 3 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-wk washout period. Postprandial glucose, insulin, glucagon, GLP-1, gastric inhibitory polypeptide (GIP), C-peptide, and triglycerides were measured over 2 h. 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.

Participants at baseline had a mean age of 33.6 ± 10.4 y, a mean body mass index of 27.1 ± 4.6kg/m², and mean fasting glucose concentrations of 94.9 ± 9.7 mg/dL. Mean glycemic responses did not differ between PomJ and sugar water across conventional glycemic metrics, including net incremental area under the curve (AUC), 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: 111.3; permutation P = 0.0002). Exploratory post hoc stratification identified heterogeneous glycemic response patterns, which were further characterized descriptively.

PomJ 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 at clinicaltrials.gov as NCT04591782.