Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.

Calcium supplementation (Calcilock), in combination with hesperidin, is effective at preserving bone in postmenopausal women.

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Hesperidin is a flavonoid derived from citrus fruits that has been shown to improve bone mass and strength in pre‐clinical studies in rodents. This double blind randomized order cross‐over study was designed to evaluate the effectiveness of hesperidin with and without a vitamin‐mineral supplement in reducing bone loss in twelve healthy post‐menopausal women using novel 41Ca methodology. Subjects who had been dosed with 41Ca (50 nCi) consumed four cookies per day containing a total of 1) 0 mg hesperidin, 2) 508 mg hesperidin or 3) 508 mg hesperidin plus a vitamin mineral supplement containing 500 mg Ca for 50 days. Urinary 41Ca/Ca was measured by Accelerator Mass Spectrometry (AMS) as an indicator of bone resorption. Decreases in daily urinary 41Ca/Ca during the course of an intervention compared with predicted change indicates improved bone retention. Intervention means are reported as relative change in bone calcium retention (%). Consumption of hesperidin plus a calcium supplement resulted in a statistically significant 5.5% improvement in bone calcium retention. There was no improvement evident with hesperidin alone. This research was supported by Nestec Ltd., Lausanne, CH