Safety evaluation of excessive intake of Hesperetin-7-Glucoside-β-Cyclodextrin Inclusion Complex in Healthy Japanese Subjects

Abstract

Background: Hesperidin, a flavonoid glycoside, is widely found in the peels and rinds of citrus fruits, offering various physiological benefits. However, its effectiveness is hindered by challenges related to insolubility and low bioavailability. To overcome these obstacles, we developed the Hesperetin-7-glucoside -β-cyclodextrin inclusion complex (HCD). This complex demonstrates superior solubility and bioavailability compared to hesperidin. In a previous study where participants consumed 300 mg/day of HCD for 12 weeks, there was a notable improvement in endothelial dysfunction. Importantly, no significant adverse clinical events were reported during this period. Objective: To evaluate the safety of the excessive intake of HCD in Healthy Japanese subjects. Methods: Fourteen healthy male and female volunteers (with a mean age of 39.1±9.1) participated in this excessive HCD intake clinical trial. Subjects took 1500 mg/day HCD, which was five times the dosage of 300 mg/day HCD, for 4 consecutive weeks. Physical examination, blood tests, and uric tests were performed during this period. Results: Results demonstrated no significant differences at 2, and 4 weeks compared to the baseline at 0 weeks with 1500 mg HCD (equivalent to 195 mg HPTG) supplementation in healthy subjects. Conclusions: It has been demonstrated that there are no safety concerns when consuming 1500 mg of HCD daily, continuously for 4 weeks. Keywords: Safety, Bioavailability, Clinical trials, Hesperidin, Food, Foods with Function Claims, Overdose supplementation, Cyclodextrin Trial registration: UMIN-CTR (Trial ID: UMIN000051960) Foundation: Taiyo Kagaku Co. Ltd.