Bioavailability and Metabolism of Ellagic Acid and Ellagitannins - Chemistry and Biology of Ellagitannins - page 291

clearing life of the metabolites (they were detected in urine for as long as
48 to 76 hours after the intake) (Cerdá et al. , 2005). The occurrence of
these metabolites in sexual tissues (uterus and prostate) has not yet been
evaluated and should be considered in further studies.
7.7 The Whole Picture of Ellagitannin Bioavailability
ETs are generally not absorbed. They release EA in the gut and this is
poorly absorbed in the stomach and small intestine, and largely
metabolized by unidentified bacteria in the intestinal lumen to produce
dibenzopyranones (urolithins). This microbial metabolism starts in the
small intestine and the first metabolites produced retain four phenolic
hydroxyls, and these are further metabolized along the intestinal tract
to remove hydroxyls units leading to urolithins A (2 hydroxyls) and B
(1 hydroxyl) in the distal parts of the colon (Fig. 7.2). The absorbed
metabolites are conjugated with glucuronic acid (one or two units),
and/or methylated (when ortho -dihydroxyphenyl moieties are present)
to give ethers. Urolithin A and B conjugates are the main metabolites
detected in plasma and urine, although some trihydroxy dibenzopyranone
derivatives (hydroxyurolithin A) or EA-dimethyl ether glucuronide
have also been detected in smaller amounts. The tetrahydroxy-
dibenzopyranones, trihydroxydibenzopyranones and EA derivatives are
not detected in peripheral plasma, but they are absorbed in the small
intestine and are transported to the liver, where they are further
metabolized and excreted with bile to the small intestine establishing an
entero-hepatic circulation that is responsible for the long life of urolithins
in plasma and urine. As far as we know, these metabolites do not
accumulate in organ tissues, with the exception of gallbladder and urine
bladder, where they are accumulated with the excretion fluids.
7.8 Conclusion
The biological activity and physiological effects of ETs and EA have to
be consistent with their bioavailability and metabolism. Thus, results
obtained from in vitro studies using cultured cells that would not be in