Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial

Hesperidin is a flavanone abundantly found in citrus fruits for which health beneficial effects have been reported. However, hesperidin shows a low bioavailability among individuals. The aim of this study was to evaluate the effects of the micronization process and 2R- and 2S-hesperidin diastereoisomers ratio on hesperidin bioavailability. In a first phase, thirty healthy individuals consumed 500 mL of orange juice with 345 mg of hesperidin, and the levels of hesperidin metabolites excreted in urine were determined. In the second phase, fifteen individuals with intermediate hesperidin metabolite levels excreted in urine were randomized in a crossover, postprandial and double-blind intervention study. Participants consumed 500 mg of the hesperidin-supplemented Hesperidin epimeric mixture (HEM), the micronized Hesperidin epimeric mixture (MHEM) and micronized 2S-Hesperidin (M2SH) in each study visit with 1 week of washout. Hesperidin metabolites and catabolites were determined in blood and urine obtained at different timepoints over a 24 h period. The bioavailability-relative urinary hesperidin excretion (% of hesperidin ingested)-of M2SH (70 +/- 14%) formed mainly by 2S-diastereoisomer was significantly higher than the bioavailability of the MHEM (55 +/- 15%) and HEM (43 +/- 8.0%), which consisted of a mixture of both hesperidin diastereoisomers. Relative urinary excretion of hesperidin metabolites for MHEM (9.2 +/- 1.6%) was significantly higher compared to the HEM (5.2 +/- 0.81%) and M2SH (3.6 +/- 1.0%). In conclusion, the bioavailability of 2S-hesperidin extract was higher compared to the standard mixture of 2S-/2R-hesperidin extract due to a greater formation of hesperidin catabolites. Furthermore, the micronization process increased hesperidin bioavailability.

Automated summary

Hesperidin, a flavanone found in citrus fruits, has been reported to have health benefits. However, its bioavailability is low among individuals. This study aimed to evaluate the impact of micronization process and the ratio of 2R- and 2S-hesperidin diastereoisomers on hesperidin bioavailability. The results showed that micronized 2S-hesperidin extract had higher bioavailability compared to the standard mixture of 2S-/2R-hesperidin extract, likely due to the increased formation of hesperidin catabolites. Micronization process also improved hesperidin bioavailability.