Effects of monoglucosyl hesperidin on human lymphatic circulatory function: A randomized placebo-controlled, double-blind, crossover trial

Monoglucosyl hesperidin promotes nitric oxide production in vascular endothelial cells and contributes to blood flow improvement and edema reduction. While preclinical studies in animal subjects have also suggested a role in promoting lymphatic drainage, its effect on human lymphatic function remains unexplored. Here, we examined the effect of monoglucosyl hesperidin intake (300 mg/day) on the lymphatic system in a controlled trial in healthy human adults (n = 30). Thoracic duct diameter was assessed by high-frequency ultrasonography as a surrogate marker of central lymphatic flow. While no effect was detected in the full cohort, in the subgroup analysis of participants with no exercise habit, monoglucosyl hesperidin intake significantly increased or showed a trend toward an increase in the thoracic duct diameter (Variation maximum value in the amount of change and the rate of change were p < 0.01 and p < 0.01, respectively; Variation minimum value in the amount of change and the rate of change were p = 0.06 and p < 0.01 respectively; ). This was consistent with the increase in lymph flow rate observed in previous animal studies, highlighting, for the first time, monoglucosyl hesperidin influencing the human lymphatic circulation function. In addition, the results suggested that thoracic duct ultrasonography had potential as a noninvasive biomarker for future interventional studies targeting lymphatic circulation function.