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Review
Flavonols, flavones and flavanols nature,
occurrence and dietary burden
Peter CH Hollman1* and Ilja CW Arts1,2
1
State Institute for Quality Control of Agricultural Products (RIKILT), Bornsesteeg 45, NL-6708 PD Wageningen, The Netherlands
National Institute of Public Health and the Environment, PO Box 1, NL-3720 BA Bilthoven, The Netherlands
Abstract: Total avonol and avone contents of foods have been determined with validated state-ofthe-art methods. Quercetin dominates, and avonol levels found in vegetables and fruits are below
10 mg kg1. However, high concentrations are found in onions (300 mg kg1), kale (450 mg kg1),
broccoli (100 mg kg1), beans (50 mg kg1), apples (50 mg kg1), blackcurrants (40 mg kg1), and tea
(30 mg l1). The dietary intake of avonols varies 10-fold between countries (660 mg day1). Flavones
are of minor importance in the diet. Tea, wine and fruits are the most important sources of avanols,
but there are gaps in our knowledge on avanol levels of many foods. The absorption of dietary
quercetin glycosides in humans ranges from 20 to 50%. The sugar moiety is an important determinant
of the bioavailability of avonols. The presence of a glucose moiety signicantly enhances absorption.
The extent of absorption of avanols in humans seems similar to that of avonols but has been little
studied. Flavonols and avanols are extensively metabolised, as only 12% of them are excreted with an
intact avonoid backbone. Hepatic biotransformations include glucuronidation and sulphatation of
the phenolic hydroxyls and O-methylation of catechol groups. Bacteria of the colon cleave the C-ring of
the avonoid nucleus to phenolic acids which are subsequently absorbed. Apart from conjugates,
virtually no metabolites have been characterised in humans. Absorption of avanols is rather fast, with
times to reach peak values between 0.5 and 4 h. Flavanols are rapidly excreted, with elimination halflives of 16 h. Quercetin glycosides show rapid to slow absorption; peak values are reached between
< 0.5 and 9 h. The type of glycoside determines the rate of absorption. Excretion of quercetin glycosides
is slow: elimination half-lives are 24 h, independent of the type of glycoside. Analytical data for
avanols in foods are needed. Tea, as an important dietary source, has to be studied. Research on the
bioavailability of avonols and avanols has to be expanded. Attention is needed for the identication
and quantication of their metabolites in body uids.
# 2000 Society of Chemical Industry
Keywords: avonols; avones; avanols; catechins; glycosides; food contents; dietary intake; bioavailability;
absorption metabolism; phenolic acids
INTRODUCTION
Flavonols, avones and avanols or catechins constitute three of the major subclasses (Fig 1) of avonoids.
Flavonols and avones have a similar C-ring structure
with a double bond at the 23 position. Flavones, as
opposed to avonols, lack a hydroxyl group at the 3position. Major avonols are quercetin (3,5,7,3',4'pentahydroxyavone), kaempferol (3,5,7,4'-tetrahydroxyavone), myricetin (3,5,7,3',4',5'-hexahydroxyavone) and isorhamnetin (3,5,7,4'-tetrahydroxy-3'methoxyavone). The most abundant avones in
plants are luteolin (5,7,3',4'-tetrahydroxyavone) and
apigenin (5,7,4'-trihydroxyavone).
The discriminating structural feature of avanols,
which they have in common with anthocyanidins only,
is the lack of an oxygen group at the 4-position of the
* Correspondence to: Peter CH Hollman, State Institute for Quality Control of Agricultural Products (RIKILT), Bornsesteeg 45, NL-6708 PD
Wageningen, The Netherlands
(Received 29 October 1999; accepted 10 November 1999)
1081
OCCURRENCE
Early interest in avonoids focused on their unequivocal identication to study evolutionary and taxonomic relationships.7 Thin layer chromatography
(TLC) methods with spectrophotometric measurements were applied.8 However, in order to be able to
evaluate the biological effects of avonoids, reliable
data on avonoid contents of common vegetables and
fruits are needed. Over the last 20 years analytical
methods have evolved and nowadays selective and
sensitive HPLC methods are used.9 Tables 1 and 2
summarise the contents of avonols, avones and
avanols of edible parts of foods. For avonols and
avones only data obtained by HPLC methods with
conrmed peak identity (photodiode array detection
or LCMS) have been selected.
Total flavonols and flavones
1082
Food
Quercetin
Kaempferol
Myricetin
Luteolin
Apigenin
Apple
Apple juice
Apricot
Bean, French
French processed
Green
Slicing
Broad
Broad processed
Broccoli
Brussels sprouts
Cabbage, green
Red
Red processed
White
Cauliower
Celery, leaf
Stalk
Cherry
Processed
Cucumber
Currant, black
Red
Endive
Grape, black
White
Grape juice
Grapefruit juice (fresh)
Kale
Leek
Lettuce
Mushroom
Onion
Orange juice
Pea
Processed
Peach
Pear
Plum
Spinach
Strawberry
Sweet pepper, red
Tea, black
Tomato
Cherry tomato
Tomato juice
Wine, red
2036
2.5
2526
39
17
16
29
20
5.5
3037
06
4.6
2.8
1015
37
813
< 1.3
1537
212
4.4
4.9
110120
1479
340347
5.7
3.4
915
68.6
1417
214
63
13
8.3
< 12
< 3.8
<7
6072
7.49
46
211470
3031
512
1416
26
4.5
4.5
6.2
3.0
7.9
200
520
511
750
1661
Food
()-Catechin
()-Epicatechin
Remarks
Reference
Apple
Apple without skin
Apple/peach juice
Apple juice
Apricot
Beer
Grape juice
Peach
Peach/grape juice
Peach nectar
Pear
Plum
Prune juice
Red grapes
Sour cherry
Sweet cherry
Tea, black
Trace17
Trace55
3
Trace2.3
2657
5
Trace2.03
50129
Trace3
Trace4.64
ND10
536
841
< 10
ND15
512
No data available
2101
10140
4
ND0.74
67171
No data available
Trace1
315
1
Trace3.60
159
016
ND
1821
4152
1449
3179
31
58
48
48, 63
31
68
48
31
48
48
31, 49
31
47
46
31
31
38
Tea, green
No data available
1094
Wine, red
Wine, white
Wine, port
ND208
716
115
1588
No data available
Trace10
16 varieties
8 varieties
Commercial juices
Commercial juices and concentrated juices
3 varieties
1 type
Commercial juices
4 varieties
Commercial juices
Commercial juices
Over 10 varieties
8 varieties
Various processing methods
Without seeds, 2 varieties
6 varieties
5 varieties
EGC: < 591
EGCg: 18229
ECg: 8110
EGC: 20287
EGCg: 60408
Over 800 types
2 types
7 types
37, 38
30, 68, 113
68
114
comparing the time course of the quercetin concentration in plasma after administration of pure quercetinb-glucoside or pure quercetin-b-rutinoside to healthy
human volunteers.89 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 (Table 3).
The bioavailability of the rutinoside was only 20% of
that of the glucoside. These pharmacokinetic data
suggest that quercetin glucoside was absorbed from
the small intestine, whereas quercetin rutinoside was
absorbed from the colon after deglycosylation.
If indeed the glucoside is absorbed from the small
intestine, this implies that the intact quercetin glucoside has to pass across the endothelial membrane for
the following reasons. One reason is that these bglycosides are resistant to hydrolysis by HCl in the
stomach.12 Another reason is that b-glycosidases are
not secreted into the small intestine.73 A third reason is
that the broad-specicity b-glucosidases needed to
hydrolyse quercetin glucoside are not bound to the
brush border membrane.90 Therefore avonoids conjugated with glucose might be carried into the smallgut enterocyte via active transport, for instance via the
intestinal Na/glucose cotransporter. The presence of
quercetin-4'-glucoside in human plasma91 also suggests that the intact glucoside may be absorbed. Model
studies showed that naphthol glucosides were transported by the active Na/glucose transporter across
the intestinal wall of rats.92 So far, only two in vitro
studies on absorption mechanisms of quercetin glucosides have been published. In everted sacs of rat
jejunum, quercetin glucosides were capable of binding
to the Na/glucose cotransporter in a sodium-dependent way.93 However, no evidence for active transport
Subjects
Quercetin aglycone
4000
< 100
Flavonol glycosides
from Gingko biloba
extract
Quercetin glucosides
from onions
28140
22.5
2
9
5
64a
68a
102 (quercetin-4'-glucoside)
200*
225*
45**
2.9
0.7
1.3
17
28
98a
90
2.5
23
Quercetin-4'-glucoside
9
9
9
100a
94a
94a
90
54
1057
9.3
6.0
< 0.5
28
22
Luteolin
50
Luteolin and
luteolin
monoglucuronide
present
Food, avonol
Quercetin glycosides
from apples
Quercetin-3-rutinoside
Tmax(h) T1/2(h)
Method
Reference
Plasma, aglycone
uorimetric
Plasma, total
avonols HPLC
115
*Plasma, total
quercetin HPLC
**Plasma,
quercetin-4'-glucoside
Plasma, total
quercetin HPLC
Plasma, total
quercetin HPLC
Plasma, total
quercetin HPLC
Serum, HPLC
87
86
88, 91
88
88, 89
88
98
Expressed as aglycone.
, data not provided.
1087
Oral dose
()-Catechin
tablet
3000 mg
15000
()-Catechin
Granulate
suspension
500; 1000;
1500 mg
Green tea
3 g lyophilised
570;
1113;
2276
685
Green tea
12
3 g lyophilised
green tea solids
Black tea
12
Green tea
3 g lyophilised
black tea solids
1.2 g lyophilised
decaffeinated
green tea
Green tea
Green tea
Green tea
18
Black chocolate 8
930 mg total
avanols
160
49 mg total
49
avanols
EGCg 88 mg
46268
EGC 82 mg
82206
ECg 33 mg
<1
EC 32 mg
4880
300 ml green tea EGCg level in
2360
brew
tea not provided
(6 g tea, 3 min)
Extract
EGCg 225; 375; 300; 1970;
(Sunphenon
525 mg
2020
DCF-1)
EGC 7.5; 12.5;
10; 44;
7.5 mg
78
1.5; 3.0; 4.5 g
EGCg 110; 220; 120; 325;
lyophilised
330 mg
320
decaffeinated
EGC 100; 200;
150; 510;
green tea
300 mg
550
EC 38; 75;
55; 190;
110 mg
190
40; 80 g black
EC 82; 164 mg
103; 196
chocolate
12
T1/2 (h)
Method
1.3
Serum, photometric,
free catechin only
1.6; 1.4; 1.3; 1.1; Serum, HPLC, free
2.0
0.9 catechin only
1
2.3
4.8
2.2
6.9
4
1
1
0.5
1.5
1.5
1.6; 2.4;
2.7
1.4; 1.8;
1.3
1.4; 1.8;
1.8
2.0; 2.6
Reference
100
99
Colorimetric (DMCA)
total avanols, free
avanols only?, no
hydrolysis described
Colorimetric (DMCA)
total avanols, free
avanols only?, no
hydrolysis described
103
Plasma, HPLC
Coulochem
electrode array, after
enzymatic hydrolysis
Plasma, HPLC photodiode
array, after acid hydrolysis
106
102
104
105
101
107
1088
After oral administration of radioactively labelled ()catechin to rodents, monkeys and man, about 50% of
the total administered radioactivity was excreted into
urine.80 This indicates that ()-catechin and its
microbial degradation products are well absorbed.
By the 1970s the pharmacokinetics of ()-catechin
as a pure compound had been studied in a limited
number of volunteers (Table 4).99101 Peak levels of
free ()-catechin in serum were reached within 2 h,
and the elimination from plasma was rather rapid with
half-lives of only 1 h (Table 4). However, the high ()catechin concentrations found by Giles and Gumma100 are probably caused by the use of a photometric
method without prior chromatographic separation.
The pharmacokinetics of EGCg, EGC, ECg and
()-epicatechin was determined in volunteers who
ingested green tea and black tea extracts, the principal
dietary sources of these avanols (Table 4).101106
EGCg showed rapid to slow absorption: the time to
reach a peak value was between 0.5 and 4 h. The peak
values obtained by Lee et al 106 and Yang et al 101 after a
dose of 100 mg EGCg were similar; however, Nakagawa and Miyazawa105 found extreme high concentrations after doses of 375 and 525 mg EGCg.
Surprisingly, Nakagawa and Miyazama105 determined
only free EGCg in plasma, whereas the other authors
used an enzymatic hydrolysis of the conjugates. No
explanation is apparent for this discrepancy. Only
Yang et al 101 determined the elimination half-life of
EGCg, which was about 5 h. Time to reach peak
values after EGC was between 1 and 2 h; the
elimination half-life was 2.53 h. The pharmacokinetics of ()-epicatechin was determined after ingestion of tea101,106 and chocolate.107 Times to reach
peak values of plasma ()-epicatechin were similar,
between 1.4 and 2.6 h. Elimination half-lives of
()-epicatechin from plasma were between 2 and 6 h.
In summary, absorption and elimination of EGCg,
EGC, ECg and ()-epicatechin are rather fast. The
present studies do not allow the pharmacokinetics of
these various avanols to be distinguished.
The potentially reduced absorption of tea avanols
from tea with milk was studied in volunteers. As for
avonols, no effect of the addition of milk to tea could
be measured.102,108
Metabolism of flavonols, flavones and flavanols
CONCLUSIONS
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