Abstract 4603: Bioavailability of ellagic acid/ellagitannins from black raspberry and pomegranate
Authors: Vadhanam Manicka V. , Aqil Farrukh , Ravoori Srivani , Gupta Ramesh C. 
Published: June 2012

Abstract
Chemoprevention by polyphenolics in fruits, particularly in berries and pomegranate, is gaining increased attention. To determine bioavailability of ellagic acid/ ellagitannins, first, we fed ACI rats with dietary black raspberry powder (5% w/w; 75 ppm ellagic acid in diet). Analysis of plasma samples by solvent extractions and HPLC showed that the levels of ellagic acid in plasma had plateaued at 3 weeks: 399 ± 85, 249 ± 98 and 344 ± 23 ng/ml at 3, 12 and 28 weeks, respectively. In the second study, we fed ACI rats with ellagic acid at 400 ppm in diet. In order to increase bioavailability, we also delivered ellagic acid systemically by subcutaneous silastic implants. The circulating levels of ellagic acid were found to plateaue at 8 weeks in the experimental diet group: 1,167 ± 171, 1,458 ± 302 and 1,272 ± 192 ng/ml at 8, 16 and 28 weeks, respectively. The ellagic acid levels, however, continued to increase when delivered by silastic implants: 53 ± 15, 130 ± 30 and 185 ± 72 ng/ml at 8, 16 and 28 weeks, respectively. Notably, it required nearly 130-fold higher dose via diet (4 mg/day) compared with implant route (0.03 mg/day) to achieve nearly 7-fold higher plasma ellagic acid levels. The oral bioavailability of ellagic acid was estimated at only 0.2%, whereas over 5% was bioavailable when administered by sustained systemic delivery. To determine if oral bioavailability of ellagic acid can be increased by administering it in the form of ellagitannins, tissues were taken from another study where female S/D rats were fed diet supplemented with equimolar doses of punicalagins (1,500 ppm) or ellagic acid (430 ppm) and treated with benzo[a]pyrene. Groups of animals were also administered punicalagins and ellagic acid via subcutaneous polycaprolactone implants (20% and 10% load, respectively). Punicalagins were undetectable by either route of administration, but its break down product ellagic acid was detected in the plasma. Dietary administration of punicalagins (17 mg/day) resulted in plasma ellagic acid levels of 3.84 ± 1.37 ng/ml corresponding to only slight (&lt;0.0002%) bioavailability. On the other hand, the polycaprolactone implant delivery (570 µg/day) resulted in &gt;150-fold higher plasma ellagic acid levels (589 ± 78 ng/ml), resulting in much higher bioavailability (0.85%). Ellagic acid administration via the diet (5 mg/day) and polycaprolactone implants (about 0.16 mg/day) showed 317 ± 39 and 673 ± 101 ng/ml plasma ellagic acid, respectively. In conclusion, i) when administered via the diet either as pure compound or as a component of black raspberry, there was no significant difference in the bioavailability of ellagic acid; however sustained, systemic delivery enhanced the bioavailability of ellagic acid by 25-fold; and ii) oral bioavailability of ellagic acid when administered as free ellagic acid was much higher than when administered as ellagitannins. (USPHS CA-18114 (RCG), CA-143676 (MVV) and the Duggan Endowment (RCG)).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4603. doi:10.1158/1538-7445.AM2011-4603