572 A. D ́avalos and M. A. Lasunci ́on
et al. 2007). In addition to antioxidant activity, long before the French paradox, wine
polyphenols had been described to elicit other biological effects including vasore-
laxation, inhibition of platelet aggregation, inhibition of cell proliferation, migra-
tion, and angiogenesis, and effects on lipid metabolism. Furthermore, consumption
of certain wine polyphenols mimics caloric restriction to extend longevity in some
organisms (Iijima et al. 2002; Stoclet et al. 2004; Vita 2005; Wood et al. 2004).
However, epidemiological observations indicate that the health benefits of wine are
noted only when consumption is moderate, because excessive alcohol intake is of
itself detrimental (Pitsavos et al. 2005; Sasaki 2000).
9E.1 Bioavailability
The biological effects of wine consumption depend on the bioavailability of the
different polyphenols it contains. The first indirect evidence of their bioavailability
came from the observation of increased plasma antioxidant capacity and reduced
susceptibility of LDL to ex vivo oxidation after consumption of red wine polyphe-
nols (Fuhrman et al. 1995; Maxwell et al. 1994; Nigdikar et al. 1998; Serafini
et al. 1998). Direct evidence of the bioavailability of wine polyphenols was obtained
by measuring their concentration in plasma or urine after the ingestion of wine or
wine polyphenols (Bell et al. 2000; Bub et al. 2001; Donovan et al. 1999). Different
groups of polyphenols from red and white wine have been reported to be absorbed
and metabolized, including anthocyanins (Bub et al. 2001; Frank et al. 2003),
flavonols (de Vries et al. 2001), stilbenes (Vitaglione et al. 2005), phenolic acids
(Caccetta et al. 2000; Simonetti et al. 2001), and a variety of other polyphenols
from different sources (Scalbert and Williamson 2000). In general, bioavailability
of polyphenols varies widely depending on the dietary sources and the forms they
contain (Manach et al. 2005). Based on ingestion of 50 mg of aglycone equiva-
lent, plasma concentration of total metabolites has been calculated to range from
0to4 mol/L (Manach et al. 2005), with isoflavones and gallic acid being better
absorbed and proanthocyanidins and anthocyanins less bioavailable.
Major factors determining the bioavailability and metabolic fate of polyphenols
in the organism include the chemical structure, the amount of polyphenol ingested,
the food matrix, and dietary factors (Bitsch et al. 2004; Goldberg et al. 2003;
Nemeth et al. 2003; Scalbert and Williamson 2000). The first step in the absorp-
tion and metabolism of dietary flavonoid glycosides involves deglycosylation in
the small intestine by lactase phlorizin hydrolase (LPH) and the cytosolic -
glucosidase (CBG) (Day et al. 2000; Nemeth et al. 2003). LPH is a membrane-
bound -glucosidase that is primarily responsible for the hydrolysis of milk lactose
and is exposed on the luminal surface of enterocytes, whereas CBG is a broad-
specificity -glucosidase and is located intracellularly (de Graaf et al. 2001; Mantei
et al. 1988). Considerable evidence is available supporting models of absorption
of dietary flavonoid glycosides and even of the 3- -glucoside oftrans-resveratrol.
In these models, polyphenol glycosides reach the small intestine, where they may
be hydrolyzed by LPH in the lumen or transported into the enterocyte by glucose