Biology Reference
In-Depth Information
Larger pharmacokinetic studies with a significant number of
volunteers are necessary to evaluate the effect of inter-individual
variability and of the concentration of free EA in the original juice on the
levels of EA detected in plasma. A recently completed pharmacokinetic
study at the University of California (
unpublished data
), using a larger
number of volunteers (
i.e.
, n = 19), resulted in pharmacokinetic
parameters for EA similar to those observed in the study with only one
human subject (Seeram
et al.
, 2004).
Regarding long-term evaluation of metabolites in plasma and urine,
three main studies should be noted. In one of these studies, healthy
volunteers consumed daily 1 L of pomegranate juice (containing 4.37
g/L of punicalagin isomers) for 5 days (Cerdá
et al.
, 2004). Punicalagin
or EA that were present in the juice were not detected in the plasma or
urine of volunteers. Three microbial ET-derived metabolites (urolithin
derivatives) were detected: 3,8-dihydroxy-6
H
-dibenzo[
b,d
]pyran-6-one
glucuronide, trihydroxy-6
H
-dibenzo[
b,d
]pyran-6-one and 3-hydroxy-6
H
-
dibenzo[
b,d
] pyran-6-one glucuronide. For those volunteers in which the
metabolites were detected, the concentration of metabolites found in
plasma ranged from 0.5 to 18.6 μM, showing evidence of a large inter-
individual variability between participants. In urine, the same
metabolites and their corresponding aglycones were detected after 1 day
of juice consumption. Total urine excretion of metabolites ranged from
0.7 to 52.7% of the ingested punicalagin. In general, the metabolites
found in humans after the pomegranate juice intake coincided with those
previously reported to be produced in rats after pomegranate husk intake
(Cerdá
et al.
, 2003a). As mentioned above, these metabolites (urolithins)
were also reported to be produced by intestinal bacteria in rats after
consumption of EA (Doyle and Griffiths, 1980).
A second study looking at ET bioavailability and metabolism was
carried out with other ET-rich foodstuffs: strawberry, raspberry, walnut
and oak-aged red wine (Cerdá
et al.
, 2005). These foodstuffs differ in the
content and type of ETs. However, it is noteworthy that the same
metabolite (urolithin A) was detected in all participants (n = 40). This led
to the proposal of the microbial metabolite urolithin A (Cerdá
et al.
,
2005a/b) as a biomarker for human exposure to dietary ETs. As already
mentioned, a large inter-individual variability was observed amongst
