Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin

Abstract

Background and objectives: The importance of quercetin and flavonoids in the diet and as food supplements is well known, and literature studies support their potential use to treat several human diseases. Many beneficial properties have been described for quercetin, so much effort has been directed into overcoming the major drawbacks of this natural compound-its poor solubility and low oral absorption. The aims of this study were to compare a new food-grade lecithin-based formulation of quercetin, Quercetin Phytosome^®, to unformulated quercetin in terms of solubility in simulated gastrointestinal fluids and oral absorption in a randomized crossover pharmacokinetic study of healthy volunteers.

Methods: The solubility of the new formulation was determined by in vitro incubation in simulated gastrointestinal fluids, and quercetin was detected by ultra performance liquid chromatography. A single-dose, randomized, six-sequence/three-period crossover clinical trial (3 × 3 × 3 crossover design) with a balanced carryover effect was conducted in healthy volunteers under fasting conditions. Twelve healthy volunteers of both sexes with an age range of 18-50 years were recruited; one dose of quercetin and two different doses of Quercetin Phytosome were administered orally as film-coated tablets. Pharmacokinetic samples were collected at twelve time points (from 0 h to 24 h) after administration, and quercetin levels were measured by HPLC/MS/MS. Data were analyzed using the Phoenix WinNonlin (v.6.4) software package, and the most significant pharmacokinetic parameters were calculated. Statistical analysis involved performing a two-way ANOVA with repeated measures followed by post hoc analysis (Tukey's test).

Results: Significant improvements in both in vitro solubility and oral absorption (in terms of both exposure and maximum concentration achieved) by healthy volunteers in a human clinical study were obtained with the Quercetin Phytosome formulation as compared to unformulated quercetin.

Conclusions: A more soluble formulation of quercetin based on lecithin, Quercetin Phytosome, has recently been developed, and was found to facilitate the attainment of very high plasma levels of quercetin-up to 20 times more than usually obtained following a dose of quercetin-when the novel formulation was administered orally in human volunteers, and it did not have any notable side effects. These results suggest that Quercetin Phytosome allows the oral administration of quercetin in a safe and bioavailable manner, thus facilitating the effective utilization of this natural compound to treat various human diseases.

Fig. 1a–d

Original MS/MS chromatograms of quercetin in plasma for a a blank sample only (left) and with the internal standard (right), b a zero sample only (left) and with the internal standard (right), c a sample with the quercetin standard corresponding to the lower limit of calibration (1 ng/mL; left) and the internal standard (right), and d a sample with the quercetin standard corresponding to the upper limit of calibration (1000 ng/mL; left) and with the internal standard (right)

Fig. 2

Pharmacokinetic profile of quercetin in the clinical study. The plasma concentrations of quercetin obtained after single oral administration of the unformulated quercetin at 500 mg/tablet and after single oral administration of its corresponding lecithin formulation, Quercetin Phytosome, at a dose of either 500 or 250 mg are shown. Data are plotted as the mean value + SD, n = 12 for each point. ^*P < 0.0001 in comparison to treatment A (Tukey’s test). ^§P < 0.005 in comparison to treatment C (Tukey’s test)