Polyphenols Bioavailability, Metabolism and Bioactivity in Humans

Francisco A. Tomás-Barberán,  Begoña Cerdá,  María M. Larrosa,  Juan C. Espín., Research Group on Quality, Safety and Bioactivity of Plant Foods.  CEBAS (CSIC) P.O. Box 164, 30100, Espinardo, Murcia, Spain. E-mail: fatomas@cebas.csic.es

Ellagic acid and ellagitannins are relevant polyphenols in strawberry and raspberry. They show high in vitro antioxidant activity (Mullen et al., 2002)  and they have been related to relevant health effects in vitro and in vivo, especially in cancers of the gastrointestinal tract. The dietary administration of strawberries and raspberries to rats has proved to inhibit events associated with both the initiation and the promotion/progression of chemically induced esophageal cancer (Kresty et al., 2001), and the antitumorigenic and antipromoting activities of ellagitannins have been reported  in mice.

However, little is known about their metabolic fate. In previous studies in rats, it was shown that ellagitanins were transformed in vivo into dibenzopyran-6-one derivatives of the urolithin B group, while the original ellagitannins or ellagic acid were very poorly absorbed and only detected in very low concentrations in urine.

In a recent study strawberries (250g) and raspberries (225g) were consumed by volunteers in a single dose and no ellagic acid nor ellagitannins were detected in plasma or urine. Only dibenzopyran-6-one glucuronides were detected. The mean percentage for metabolite excretion ranged from 2.8 % in strawberries to 3.4% in raspberries regarding the ingested ellagitannins. Considerable inter-individual differences were noted, supporting the involvement of the colonic microflora in ellagitannin metabolism (Cerdá et al., 2005). The production of urolithin B from ellagitannins by the human colon microflora has been demonstrated by incubation of ellagic acid and ellagitannins with fecal samples from several healthy donors under anaerobic conditions (Figure 1). These results indicate that urolithin B, a previously described antiangiogenic and hyaluronidase inhibitor compound, is a biomarker of human exposure to dietary ellagitannins. The antioxidant and anticarcinogenic effects of dietary ellagitannins and ellagic acid should be considered in the gastrointestinal tract whereas the study of potential systemic activities should be focused on the bioavailable urolithin B derivatives.

XXX No picture available
Figure 1. Metabolism of ellagitannins and ellagic acid to urolithin B.


Cerdá, B.; Tomás-Barberán, F.A. ; Espín, J.C. ‘Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts and oak-aged wine in humans: Identification of biomarkers and individual variability’, J. Agric. Food Chem. 2005, 53, 227-235.

Kresty, L.A.; Morse, M.A.; Morgan,C.; Carlton, P.S.; Lu, J.; Gupta, A.; Blackwood, M.; Stoner, G.D. ‘Chemoprevention of esophageal tumorigenesis by dietary administration of luophilised black raspberries’. Cancer Res., 2001, 61, 6112-6119.

Mullen, W.; McGinn, J.; Lean, M.E.J., MacLean, M.R.; Gardner, P.; Duthie, G.G.; Crozier, A. ‘Ellagitannins, flavonoids and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties’. J. Agric. Food Chem., 2002, 50, 5191-5196.

Acknowledgements:  The authors are grateful to the Spanish CICYT for financial support of this work (projects AGL2003-02195 and AGL2004-03989).

Keywords: Ellagitannin; ellagic acid; polyphenols; metabolism; colonic microflora; urolithin B; bioavailability; antioxidant; strawberry; raspberry.