Download Absorption, Bioavailability, and Metabolism of Flavonoids

Pharmaceutical Biology
2004, Vol. 42, Supplement, pp. 74–83
Absorption, Bioavailability, and Metabolism of Flavonoids
Peter C.H. Hollman
Food Bioactives Group, RIKILT–Institute of Food Safety, Wageningen, The Netherlands
Abstract
To unravel mechanisms of action of dietary flavonoids in
their potential role in disease prevention, it is crucial to
know the factors that determine their release from foods,
their extent of absorption, and their fate in the organism.
Research on absorption, metabolism, and bioavailability
of flavonoids will answer these questions. The subclass,
flavonols, with quercetin as the major dietary flavonol,
was the first to be studied, and information on other subclasses of flavonoids is emerging. Most flavonoids, except
for the subclass of catechins, are present in plants bound
to sugars as b-glycosides. This structural feature determines whether the flavonoid can be absorbed from the
small intestine or has to go to the colon before absorption
can occur. Generally, but exceptions have been described,
glucosides are the only glycosides that can be absorbed
from the small intestine. Absorption from the small intestine is more efficient than from the colon and will lead to
higher plasma values. After absorption from the small
intestine, flavonoids are conjugated with glucuronic acid
or sulfate or O-methylation may occur. The conjugation
reactions, which occur in the small intestine upon absorption, are very efficient. As a result, no free flavonoid aglycones can be found in plasma or urine, except for
catechins. Plasma concentrations due to a normal diet
will be less than 1 mM. Flavonoids that cannot be
absorbed from the small intestine, and absorbed flavonoids secreted with bile, will be degraded in the colon
by microorganisms, which will break down the flavonoid
ring structure. The resulting phenolic acids have partly
been characterised. These phenolic acids can be absorbed
and have been measured in plasma and urine. Future
research will need to address tissue distribution, cellular
uptake, and cellular metabolism.
Keywords: Absorption, bioavailability, flavonoids, glucuronides, glycosides, phenolic acids, polyphenols, metabolism.
Introduction
It is generally recognized that an increased consumption
of vegetables and fruits protects against cancer and
cardiovascular diseases (CVD) (Ness & Powles, 1997;
Research WCRF=AICR, 1997; Ness et al., 1999). An
attractive hypothesis is that vegetables and fruits contain
bioactive compounds that have a protective effect.
Flavonoids, a large group of natural antioxidants ubiquitous in a diet high in plant foods (Kühnau, 1976), may
contribute to this protective effect. In addition to their
antioxidant properties, flavonoids show a number of
effects in animal models and in in vitro systems which
might explain their potentially beneficial role (Nijveldt
et al., 2001).
Flavonoids are secondary plant metabolites, which
together with other plant phenols share a common origin:
the amino acid phenylalanine (Parr & Bolwell, 2000). As
a result, these phenols are derived from a common building
block in their carbon skeleton: the phenylpropanoid unit,
C6 C3. Biosynthesis according to this pathway produces
the large variety of plant phenols: cinnamic acids
(C6 C3), benzoic acids (C6 C3, or C6 C1), flavonoids
(C6 C3 C6), proanthocyanidins (C6 C3 C6)n, stilbenes
(C6 C2 C6), coumarins (C6 C3), lignans (C6 C3
C3 C6), and lignins (C6 C3)n. Within each family of plant
phenols many compounds may exist. Over 4000 different
flavonoids (Fig. 1) have been described as occurring in
plants (Harborne & Baxter, 1999).
To elucidate the role of dietary flavonoids in human
health, it is important to know the concentrations and
forms that are present in plasma and tissues after ingestion of these flavonoids with the diet. Therefore, it is
essential to study their absorption, metabolism, and
bioavailability. The current paper summarizes the
current knowledge on human absorption, metabolism,
and bioavailability of dietary flavonoids.
Accepted: September 15, 2004
Address correspondence to: Peter C.H. Hollman, Food Bioactives Group, RIKILT–Institute of Food Safety, Bornsesteeg 45, 6708 PD
Wageningen, The Netherlands. E-mail: [email protected]
DOI: 10.1080=13880200490893492 # 2004 Taylor & Francis Ltd.
Absorption, bioavailability, and metabolism of flavonoids
75
Figure 1. Subclasses of flavonoids. Classification is based on variations in the heterocyclic C-ring.
Absorption
Before dietary flavonoids can be absorbed from the gut,
they must be released from plant foods by chewing,
action of the digestive juices in the gastrointestinal
tract, and finally the microorganisms of the colon. It
can be envisaged that this release from the plant tissues,
the so-called food matrix, depends on the type of plant
food, its processing conditions, and the presence of
other dietary components. The absorption of the flavonoid liberated from the food will depend on its physicochemical properties such as molecular size and
configuration, lipophilicity, solubility, and pKa. To date,
only fragmentary information is available on the effect
of the plant food matrix on absorption. Well-designed
studies that addressed this issue have not been reported.
Role of the flavonoid structure: Glycosides
and oligomers
Glycosides
Most flavonoids, except catechins, are usually present in
the diet as b-glycosides (Fig. 2). Glycosides were
considered too hydrophilic for absorption by passive
diffusion in the small intestine, thus only aglycones were
likely to be absorbed. Studies with germ-free rats showed
that large amounts of unchanged glycosides were
excreted with feces, whereas only small amounts of
glycosides were found in feces of rats with a normal
microflora (Griffiths & Barrow, 1972). Thus, it was
thought that the glycosylated flavonoids were only
marginally absorbed. However, this view on absorption
of glycosides had to be revised.
A study with ileostomy subjects who lack a colon with
bacteria showed unexpectedly high absorption of
quercetin-glucosides (quercetin-40 -glucoside and quercetin3,40 -bis-glucoside) from onions (52%) (Hollman et al.,
1995). These data also suggested that absorption of quercetin glucosides takes place in the small intestine, a novel
finding. This was confirmed in a human pharmacokinetic
study (Hollman et al., 1997). To explain this remarkable
finding that the hydrophilic quercetin glucoside is transported across the small intestine, it was proposed that the
intestinal Naþ-dependent glucose cotransporter (SGLT1)
was involved (Hollman et al., 1999). This would imply that
intact quercetin glucoside can be transported across the
enterocyte and possibly could appear in the plasma. However, intact quercetin-3-glucoside was absent in plasma
after supplementation of volunteers with quercetin-3-glucoside, which does not strengthen the SGLT1 hypothesis
(Sesink et al., 2001). An alternative mechanism states that
quercetin glucosides are hydrolyzed by lactase phloridzin
hydrolase (LPH), a b-glucosidase on the outside of the
brush border membrane of the small intestine (Day et al.,
2000). Subsequently, the liberated aglycone can be
absorbed across the small intestine. It was confirmed in
an in situ rat perfusion model that LPH is predominantly
(> 75%) involved in the absorption of quercetin-3glucoside across the small intestine (Sesink et al., 2003).
The substrate specificity of this LPH enzyme varied
significantly in a broad range of glycosides (glucosides,
galactosides, arabinosides, xylosides, rhamnosides, and
galactosides) of flavonols, flavones, flavanones, isoflavones, and anthocyanins (Németh et al., 2003). Only
glucosides were efficiently hydrolyzed by LPH, more-orless independent of the aglycone part of the glucoside.
76
P.C.H. Hollman
Figure 2. Structures of two glycosides, quercetin-40 -b-glucoside and quercetin-3-b-rutinoside, and a proanthocyanidin trimer C1.
Absorption, bioavailability, and metabolism of flavonoids
Noticeable exceptions were the anthocyanin cyanidin3-glucoside where no hydrolysis was detected, and the
isoflavone daidzein-7-glucoside with a low hydrolysis rate.
Glycosides that are not substrates for these two
enzymes will be transported toward the colon where bacteria are able to hydrolyze flavonoid glycosides but at the
same time will degrade the liberated flavonoid aglycones
(Scheline, 1973). Because the absorption capacity of the
colon is far less than that of the small intestine, only
marginal absorption of these glycosides is to be expected.
As an example, the bioavailability of pure quercetin-3b-rutinoside (no substrate for either LPH or SGLT1)
administered to volunteers was only 20% of that of pure
quercetin-40 -b-glucoside (Hollman et al., 1999). These
data strongly indicate that the sugar moiety of quercetin
glycosides is a major determinant of their absorption and
bioavailability.
Oligomers
In contrast with other flavonoids, catechins occur as
aglycones and galloylated forms in foods. Pharmacokinetic data point to absorption from the small intestine
of both the aglycones and the galloylated forms (Lee
et al., 1995). Human data on the quantity of catechins
that are absorbed are lacking. However, besides aglycones, catechins occur in plant foods as oligomers of
up to 17 catechin units: the proanthocyanidins (Fig. 2).
In vitro studies with Caco-2 cells showed that only dimers
and trimers were able to pass across monolayers of these
cells (Déprez et al., 2001). Indeed, procyanid dimer B2
[epicatechin-(4b!8)-epicatechin] was detected in human
plasma after ingestion of a cocoa beverage (Holt et al.,
2002). It has been suggested that oligomers can be hydrolyzed to monomers and dimers due to the acidic conditions in the stomach (Spencer et al., 2000). However,
sampling of human gastric juice showed that hydrolysis
of proanthocyanidins does not occur in vivo (Rios et al.,
2002). It can be concluded that only proanthocyanidins
up to three catechins are absorbable from the colon.
Larger molecules will reach the colon where they will
be degraded by bacteria.
Role of other dietary components
Interaction of proteins with the absorption of polyphenols might be expected, because polyphenols can bind
proteins efficiently. It was found in humans that addition
of milk to black tea did not change the area under the
curve of the plasma concentration-time curves of flavonols and catechins (van het Hof et al., 1998; Hollman
et al., 2001). Thus, absorption of flavonols and catechins
was independent of the addition of milk. The role of
alcohol in the absorption of wine flavonoids has been
investigated, because ethanol could increase their absorp-
77
tion by improving the solubility. However, no increase in
plasma catechin could be measured (Donovan et al.,
1999).
Bioavailability
Dietary flavonol glycosides showed very rapid to very
slow absorption in man. Times to reach peak concentrations (Tmax) were between < 0.5 and 9 h (Table 1). The
bioavailability of quercetin glucosides from onions was
superior. Bioavailability of various quercetin glycosides
(b-galactosides and b-xylosides) from apples and of pure
quercetin rutinoside was only 30% of that from onions
(Hollman et al., 1997). Thus, the sugar moiety of quercetin glycosides seemed to be an important determinant
of their bioavailability, which was confirmed when pure
quercetin-b-glucoside or pure quercetin-b-rutinoside
was administered to healthy human volunteers (Hollman
et al., 1999). The peak concentration of quercetin (Cmax)
in plasma was 20-times higher and reached (Tmax) more
than 10-times faster after intake of the glucoside than
after the rutinoside. These pharmacokinetic data suggest
that quercetin glucoside was absorbed from the small
intestine, whereas quercetin rutinoside was absorbed
from the colon after deglycosylation. Evidently, the
sugar moiety played no role in the elimination of quercetin from plasma: elimination half-life was about 20 h
for all glycosides (Table 1). This is consistent with the
observation that quercetin glucosides do not circulate
in the blood (Sesink et al., 2001). Apparently, the sugar
part only plays a role upon absorption.
Meanwhile, bioavailability studies have been performed with flavonoids of all subclasses, except for flavones (Table 1). For comparison reasons, Cmax=Dose is
calculated and shown in this table to give some insight
into the relative bioavailability of the flavonoids tested.
However, a proper comparison can only be made when
areas under the plasma concentration-time curve
(AUC) are calculated. The Cmax values in this table give
insight in the upper levels of flavonoids that will be circulating due to a diet rich in flavonoids. As an example,
after ingestion of a solution of 150 mg (325 mmol) pure
quercetin-3-glucoside, a plasma concentration of 5 mM
quercetin was reached. However, such high quantities of
quercetin will never be ingested via an average diet. The
average dietary intake of quercetin in The Netherlands is
on average only 23 mg (Hertog et al., 1993), which would
predict a plasma value of only 1 mM quercetin, assuming
that all dietary quercetin is present as quercetin-glucoside,
the most bioavailable compound, and is taken as a single
dose. Therefore, daily plasma levels of quercetin will be
substantially lower than 1 mM.
Catechins are quite rapidly absorbed, suggesting
absorption from the small intestine. The galloylated
EGCg is not different in this respect. Bioavailability of
78
Soy milk
Pure compound
Pure compound
Soy milk
Pure compound
Pure compound
70
186
62
98
196
55
137
182
24.4
68.6
concentrate
concentrate
concentrate
concentrate
Black
Black
Black
Black
currant
currant
currant
currant
727
166
630
443
120
143
565
467
395
230
284
225
325
288
325
331
311
662
662
Dose (mmol)
Orange juice
Orange juice
Chocolate
Chocolate
Red wine
Green tea
Chocolate
Green tea
Green tea
Green tea
Pure compound
Onions
Apples
Various foods
Pure compound
Pure compound
Pure compound
Pure compound
Black tea
Source
0.74
0.87
0.40
0.79
0.92
0.2
0.05
0.07
0.005
0.02
1.3
0.2
0.08
0.04
0.09
0.43
0.7
0.73
0.17
0.31
0.076
0.74
0.30
0.4
5.0
4.5
0.2
2.0
1.0
Cmax (mM)
10.6
4.7
6.5
8.1
4.7
3.6
0.3
0.4
0.2
0.3
1.8
1.2
0.1
0.09
0.75
3.0
1.2
1.6
0.4
1.3
0.27
3.3
0.9
1.4
15
14
0.6
3.0
1.5
Cmax=Dose (mM=mmol) 103
6.5
7.4
4–6
6.5
7.2
4–6
1.5
1.8
1.3
1.5
5.8
5.0
2
2
1.5
1.3
3
1.3
1.6
2
1.6
0.7
2.2
Tmax < 7b
0.6
0.5
6.0
7
4
Tmax (h)
—
—
—
—
—
—
3.5
3.2
1.3
4.2
—
—
—
—
3.1
3.0
—
1.7
3.4
—
3.7
28
23
—
19
19
28
7
7
Thalf (h)
et
et
et
et
al.
al.
al.
al.
(2001)
(2001)
(2001)
(2001)
Xu et al. (1994)
Setchell et al. (2003)
Izumi et al. (2000)
Xu et al. (1994)
Setchell et al. (2003)
Izumi et al. (2000)
Matsumoto
Matsumoto
Matsumoto
Matsumoto
Manach et al. (2003)
Manach et al. (2003)
Steinberg et al. (2002)
Holt et al. (2002)
Donovan et al. (1999)
Lee et al. (2002)
Richelle et al. (1999)
Lee et al. (2002)
Lee et al. (2002)
Unno et al. (1996)
Lee et al. (2002)
Hollman et al. (1997)
Hollman et al. (1997)
Manach et al. (1998)
Olthof et al. (2000)
Olthof et al. (2000)
Hollman et al. (1999)
Graefe et al. (2001)
Graefe et al. (2001)
References
Cmax, peak level; Tmax, time to reach peak level; Thalf, elimination half life; —, data not given; EGCg, ()-epigallocatechin gallate; EGC, ( )-epigallocatechin; EGCg,
()-epicatechin gallate.
a
Adapted from Gonthier (2003).
b
Plasma only sampled at 3, 7, and 20 h after the test meal.
Daidzein-7-glucoside
Genistein-7-glucoside
Daidzein
Flavanones
Hesperitin-7-rutinoside
Naringin-7-rutinoside
Anthocyanins
Cyanidin-3-rutinoside
Delphinidin-3-rutinoside
Cyanidin-3-glucoside
Delphinidin-3-glucoside
Isoflavones
Genistein
Proanthocyanidins
Dimer B2
EGC
EGCg
Catechins
(þ)-Catechin
()-Epicatechin
Q-3-glucoside
Q-40 -gllucoside
Q-3-rutinoside
Flavonols
Quercetin (Q)
Flavonoid
Table 1. Plasma concentrations and kinetics after single-dose administration of flavonoids to humansa.
Absorption, bioavailability, and metabolism of flavonoids
the various catechin monomers seems to be quite similar.
However, dimerization reduces bioavailability.
Flavanone rutinosides are slowly absorbed, suggesting a
similar role of the attached disaccharide as with flavonols.
Isoflavones show the highest bioavailability of all subclasses of flavonoids. Bioavailability does not differ
between aglycones and glucosides. Remarkably, the
absorption of both the aglycones and the glucosides is
quite slow, suggesting absorption from the colon. This
fits with the finding that LPH has a weak affinity for
daidzein-7-glucoside (Németh et al., 2003), and also
would predict a low affinity of LPH for genistein-7glucoside.
Anthocyanins are quite rapidly absorbed, but their
bioavailability seems to be the lowest of all flavonoids.
It is not clear yet whether the problematic quantification
of anthocyanins in plasma and urine causes these low
values. Development of reliable analytical protocols
should have a high priority.
The elimination half-lives of flavonols are quite
different from those of the other flavonoid subclasses.
Catechins and anthocyanins have elimination half-lives
that are 5- to 10-fold lower than those of flavonols. No
data are available for the other subclasses, but plasma
profiles suggest that elimination is comparable with that
of catechins and anthocyanins.
Metabolism
In the metabolism of flavonoids, two compartments are
considered. The first compartment consists of tissues
such as the small intestine, liver, and kidneys. The colon
constitutes the second compartment (Fig. 3). Flavonoids
that are unabsorbable from the small intestine and
flavonoids that have been absorbed and then secreted
with bile will reach the colon. The significance of biliary
secretion in humans remains to be determined, but in rats
about 40% of the absorbed (þ)-catechin was secreted
with bile into the small intestine (Hackett, 1986).
Metabolism in tissues: Side groups are attached
or detached
In the first compartment, mainly the small intestine and
liver, biotransformation enzymes act upon flavonoids
and their colonic metabolites. The kidney also contains
enzymes capable of biotransformation of flavonoids.
Conjugation of the polar hydroxyl groups with glucuronic acid, sulfate, or glycine has been reported for flavonoids and for their colonic metabolites (Hollman &
Katan, 1998). In addition, O-methylation by the enzyme
catechol-O-methyltransferase plays an important role in
the inactivation of the catechol moiety, that is, the two
adjacent (ortho) aromatic hydroxyl groups, of flavonoids
and their colonic metabolites. Recently, deglycosylation
79
of glycosides in the brush border membrane of the small
intestine was demonstrated (Day et al., 2000).
The conjugation reactions are very efficient in
humans, evidenced by the fact that flavonoids predominantly occur in plasma and urine as conjugates, and that
it is difficult to detect flavonoid aglycones in plasma,
because they are mostly below the limit of detection of
the analytical methods used. The presence of flavonoid
conjugates in humans, including O-methylated conjugates, is apparent from differential High Performance
Liquid Chromatography (HPLC) analyses with and
without hydrolysis of the sample with a mixture of
b-glucuronidases and sulfatases: flavonols (Manach
et al., 1998; Olthof et al., 2000; Graefe et al., 2001;
Stahl et al., 2002), flavones (Shimoi et al., 1998), catechins (Lee et al., 1995; Lee et al., 2002), flavanones
(Manach et al., 2003), and anthocyanins (Felgines et al.,
2003). In a number of human intervention studies the
nature of the conjugates has been identified. Major conjugates of quercetin after onions supplementation were
the 30 -sulfate, the 30 -methoxy-3-glucuronide, and the
3-glucuronide (Day et al., 2001). The 30 -sulfate could not
be confirmed with Liquid Chromatography-Mass Spectometry=Mass Spectometry (Tandem Mass Spectometry)
(LC-MS=MS) in another study (Wittig et al., 2001).
Human studies that identified the circulating plasma
conjugates for other flavonoids mainly found glucuronides
for isoflavones (Doerge et al., 2000; Setchell et al., 2001;
Shelnutt et al., 2002; Zhang et al., 2003), for catechins
(Baba et al., 2000; Lee et al., 2002), for flavanones
(Manach et al., 2003), and for anthocyanins (Wu et al.,
2002; Felgines et al., 2003). Catechins seem to take a separate position in conjugation efficiency: depending on the
type of catechin from 10% up to 80% can be present as
the aglycone in plasma (Lee et al., 2002). Conjugation of
phenolic acids, the colonic metabolites of flavonoids, also
seems to occur less efficiently, with conjugation percentages
ranging from 13% to 100%, depending on the type of
phenolic acid (Olthof et al., 2003).
It also appears that deglycosylation of flavonol glycosides is very efficient, as glycosides were absent in plasma
after supplementation of volunteers with quercetin glucosides (Sesink et al., 2001). However, anthocyanins take
a different position. Evidence is accumulating that
anthocyanidin glycosides are able to at least partly
withstand deglycosylation reactions in humans. The
appearance of peonidin-3-glucoside, even peonidin-3sambubioside (sambubioside is a disaccharide!) (Wu
et al., 2002) and pelargonidin-3-glucoside (Felgines
et al., 2003) in urine has been confirmed with LC-MS.
Metabolism in the colon: The flavonoid nucleus is split
Microorganisms degrade the flavonoid molecule in the
course of which the heterocyclic oxygen containing ring
is split. The subsequent degradation products can
80
P.C.H. Hollman
Figure 3. Compartments involved in the metabolism of plant phenols. A flavonoid that is well absorbed in the small intestine (e.g.,
quercetin-3-glucoside) is chosen as an example. White arrows depict the flow of flavonoids with an intact ring system inside the body.
Gray arrows depict the flow of colonic metabolites, the phenolic acids. The width of the arrows indicate the relative importance of
these two different classes of metabolites, however, experimental data are still far from complete (Hollman, 2001).
evidently be absorbed because they are found in urine and
plasma (Rechner et al., 2002; Olthof et al., 2003). These
include a variety of hydroxylated phenyl carboxylic acids.
The type of ring fission depends on the type of flavonoid:
three schemes have been described based on animal
experiments (Hollman & Katan, 1998). Flavonols are
degraded to phenylacetic acids and phenylpropionic
acids, however, these phenylpropionic acids could not
be confirmed in a human study (Olthof et al., 2003). Ring
fission of catechins produces valerolactones (a benzene
ring with a side chain of five C-atoms), and phenylpropionic acids. Flavones and flavanones follow a scheme producing phenylpropionic acids. These phenylcarboxylic
acids are subject to further bacterial degradation and to
enzymatic transformations in body tissues. As a result,
the phenylpropionic acids will be oxidized to benzoic
acids. Recent studies confirmed that this scheme also
applies to humans (Rechner et al., 2002; Olthof et al.,
2003). There was one exception; in humans as opposed
to rodents, only phenylacetic acids were formed after
ingestion of quercetin-rutinoside (Olthof et al., 2003).
Although about 60 putative phenolic acid metabolites
potentially could be identified and quantified, only a limited number of phenolic acids actually were found (Olthof
et al., 2003). The glycine ester of benzoic acid, hippuric
acid, proved to be a very important metabolite in humans
after ingestion of tea, but not after quercetin rutinoside. It
was shown that microorganisms in the colon play an
essential role in the metabolism of flavonoids into phenolic acids (Olthof et al., 2003).
Apart from degrading the flavonoid ring system,
colonic bacteria produce glycosidases, glucuronidases,
and sulfatases that can strip flavonoid conjugates of their
sugar moieties, glucuronic acids, and sulfates (Scheline,
1973). Human intestinal bacteria are able to hydrolyse
O-glycosides (Scheline, 1973) as well as C-glycosides
(Hattori et al., 1988).
Extent of metabolism
Flavonols were the first to be studied and showed a
rather low urinary excretion in humans. Only 0.1%
to 3.6% of the ingested dietary quercetin was excreted
as quercetin conjugates in urine (Table 2). Urinary
excretion will correlate with the amount of intact
quercetin in plasma. Because absorption of quercetin
glucosides is quite high (up to 50%), whereas excretion
of intact quercetin in urine is low, this points to extensive metabolism of quercetin. Additional subclasses
have been studied with volunteers, and urinary excretion
of metabolites with an intact flavonoid structure have
been quantified (Table 2). It is clear that excretion of
isoflavones is the highest of all flavonoids. Although
the bioavailability of isoflavones is high (Table 1),
flavonols glucosides show a higher bioavailability
but a smaller urinary excretion. This would imply
that the extent of metabolism by which the ring system is modified is lower with isoflavones than with
flavonols.
Absorption, bioavailability, and metabolism of flavonoids
Table 2. Urinary excretion of metabolites with an intact flavonoid structure (as a percentage of the ingested dose) after various flavonoid supplements.
Flavonoid
subclass
Excretion (%)
References
Flavonols
0.07–3.6
Catechins
1.1–10
Flavanones
Anthocyanins
4–8
0.1–5
Hollman et al. (1997);
Olthof et al. (2000);
de Vries et al. (1998);
de Vries et al. (2001)
Lee et al. (1995);
Donovan et al. (2002);
Warden et al. (2001)
Manach et al. (2003)
Felgines et al. (2003);
Wu et al. (2002);
Matsumoto et al. (2001);
Lapidot et al. (1998)
Zhang et al. (2003);
Xu et al. (1994);
Setchell et al. (2003)
Isoflavones
9–30
Conclusions
Starting with quercetin, knowledge on bioavailability
and metabolism of all subclasses of flavonoids has been
increasing steadily during the past 5 years. For a proper
evaluation of their potential health effects, this information is essential and still has to be extended. We need
more data on the concentrations and metabolic forms
that tissues and cells are exposed to after ingestion of flavonoids via the diet. Then the next step can be taken to
study the potential biological effects at the tissue and
cellular level. New genomic techniques will give tremendous opportunities to explore this field. For this type
of research, it is essential to know which metabolites will
reach tissues and cells, at what concentrations, and to
what extent they are taken up and modified in cells after
a flavonoid-rich diet. The high-throughput genomics
tools will then be able to increase our understanding
on how flavonoids affect metabolic pathways and, as a
consequence, affect human health.
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(2000): Dietary flavonoid and isoflavone glycosides
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