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, that have been linked to metabolic benefits. However, evidence regarding its acute metabolic effects remains inconclusive.

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.

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.

Participants at baseline had a mean age of 33.6±10.4years, a mean BMI of 27.1±4.6kg/m², 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.

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.